Alport syndrome in children clinical guidelines. Alport syndrome treatment

The genetic basis of the disease is a mutation in the a-5 gene of the type IV collagen chain. This type is universal for the basement membranes of the kidney, cochlear apparatus, lens capsule, retina and cornea of ​​the eye, which has been proven in studies using monoclonal antibodies against this collagen fraction. Recently, the possibility of using DNA probes for the prenatal diagnosis of hereditary nephritis has been pointed out.

The importance of testing all family members using DNA probes to identify carriers of the mutant gene is emphasized, which is of great importance when conducting medical genetic counseling for families with this disease. However, up to 20% of families do not have relatives suffering from kidney disease, which suggests a high frequency of spontaneous mutations of the abnormal gene. Most patients with hereditary nephritis have families with kidney disease, hearing loss and vision pathology; related marriages between people with one or more ancestors are important, since in the marriage of related individuals, the probability of receiving the same genes from both parents increases. Autosomal dominant and autosomal recessive and dominant, X-linked transmission pathways have been established.

In children, three variants of hereditary nephritis are more often distinguished: Alport syndrome, hereditary nephritis without hearing loss, and familial benign hematuria.

Alport syndrome — hereditary nephritis with hearing loss. It is based on a combined defect in the collagen structure of the basal membrane of the glomeruli of the kidneys, structures of the ear and eye. The gene for classic Alport syndrome is located at the locus 21-22 q of the long arm of the X chromosome. In most cases, it is inherited in a dominant type linked to the X chromosome. In this regard, in men, Alport syndrome is more severe, since in women the function of the mutant gene is compensated by a healthy allele of the second, intact chromosome.

The genetic basis for the development of hereditary nephritis are mutations in the genes of type IV collagen alpha chains. Six a-chains of type IV collagen G are known: the genes for a5- and a6-chains (Col4A5 and Col4A5) are located on the long arm of the X chromosome in the zone 21-22q; genes of а3- and а4-chains (Сol4A3 and Сol4A4) — on the 2nd chromosome; genes a1- and a2-chains (Col4A1 and Col4A2) - on the 13th chromosome.

In most cases (80-85%), an X-linked type of inheritance of the disease is detected, associated with damage to the Col4A5 gene as a result of deletion, point mutations, or splicing disorders. Currently, more than 200 mutations of the Col4A5 gene have been found, which are responsible for impaired synthesis of a5-chains of type IV collagen. With this type of inheritance, the disease manifests itself in children of both sexes, but in boys it is more severe.

Mutations in the loci of the Col4A3 and Col4A4 genes responsible for the synthesis of a3- and a4-type IV collagen chains are inherited autosomal. According to studies, an autosomal dominant type of inheritance is observed in 16% of cases of hereditary nephritis, autosomal recessive - in 6% of patients. About 10 mutation variants of the Col4A3 and Col4A4 genes are known.

The result of mutations is a violation of the assembly processes of type IV collagen, leading to a violation of its structure. Collagen type IV is one of the main components of the glomerular basement membrane, the cochlear apparatus and the lens of the eye, the pathology of which will be detected in the clinic of hereditary nephritis.

Type IV collagen, which is part of the glomerular basement membrane, consists mainly of two a1-chains (IV) and one a2-chain (IV), and also contains a3, a4, a5-chains. Most often, in X-linked inheritance, the mutation of the Col4A5 gene is accompanied by the absence of a3-, a4-, a5- and a6 chains in the structure of type IV collagen, and the number of o1- and a2-chains in the glomerular basement membrane increases. The mechanism of this phenomenon is unclear, it is assumed that the cause is post-transcriptional changes in mRNA.

The absence of a3-, a4- and a5-chains in the structure of type IV collagen of the glomerular basement membranes leads to their thinning and fragility in the early stages of Alport's syndrome, which is clinically manifested more often by hematuria (less often hematuria with proteinuria or only proteinuria), hearing loss and lenticonus. Further progression of the disease leads to thickening and impaired permeability of the basement membranes in the later stages of the disease, with the growth of type V and VI collagen in them, manifested in an increase in proteinuria and a decrease in renal function.

The nature of the mutation underlying hereditary nephritis largely determines its phenotypic manifestation. With deletion of the X chromosome with simultaneous mutation of the Col4A5 and Col4A6 genes responsible for the synthesis of a5- and a6-chains of type IV collagen, Alport's syndrome is combined with leiomyomatosis of the esophagus and genital organs. According to studies with a mutation in the Col4A5 gene associated with a deletion, there is a greater severity of the pathological process, a combination of renal damage with extrarenal manifestations and early development of chronic renal failure, compared with a point mutation of this gene.

Morphologically, electron microscopy reveals thinning and stratification of glomerular basement membranes (especially lamina densa) and the presence of electron-dense granules. Glomerulus involvement can be heterogeneous in the same patient, ranging from minimal focal mesangial involvement to glomerulosclerosis. Glomerulitis in Alport syndrome is always immuno-negative, which distinguishes it from glomerulonephritis. Characterized by the development of atrophy of the tubules, lymphohistiocytic infiltration, the presence of "foam cells" with lipid inclusions - lipophages. With the progression of the disease, thickening and pronounced destruction of the basement membranes of the glomeruli is revealed.

Certain shifts in the state of the immune system are revealed. In patients with hereditary nephritis, a decrease in the level of Ig A and a tendency to increase the concentration of IgM in the blood were noted, the level of IgG can be increased in the early stages of the disease and decrease in the later stages. It is possible that an increase in the concentration of IgM and G is a kind of compensatory reaction in response to IgA deficiency.

The functional activity of the T-lymphocyte system is reduced; there is a selective decrease in B-lymphocytes responsible for the synthesis of Ig A, the phagocytic link of immunity is disturbed, mainly due to disruption of the processes of chemotaxis and intracellular digestion in neutrophils

In the study of kidney biopsy in patients with Alport's syndrome, according to electron microscopy, ultrastructural changes in the glomerular basement membrane are observed: thinning, disruption of the structure and splitting of glomerular basement membranes with a change in its thickness and uneven contours. In the early stages of hereditary nephritis, the defect determines the thinning and fragility of the glomerular basement membranes.

Thinning of the glomerular membranes is more benign and is more common in girls. A more constant electron microscopic sign in hereditary nephritis is the splitting of the basement membrane, and the severity of its destruction correlates with the severity of the process.

Causes and mechanism of development of Alport syndrome

Alport syndrome is caused by mutations in the COL4A4, COL4A3, COL4A5 genes responsible for collagen biosynthesis. Mutations in these genes disrupt the normal synthesis of type IV collagen, which is a very important structural component of basement membranes in the kidneys, inner ear and eyes.

Basement membranes are thin film structures that support tissues and separate them from each other. In violation of the synthesis of type IV collagen, the glomerular basement membranes in the kidneys are not able to normally filter toxic products from the blood, passing proteins (proteinuria) and red blood cells (hematuria) into the urine. Abnormalities in type IV collagen synthesis lead to kidney failure and kidney failure, which is the main cause of death in Alport syndrome.

Clinic

Hematuria is the most common and early manifestation of Alport's syndrome. Microscopic hematuria is observed in 95% of women and in almost all men. In boys, hematuria is usually detected in the first years of life. If a boy does not have hematuria in the first 10 years of life, then American experts recommend that he is unlikely to have Alport syndrome.

Proteinuria is usually absent in childhood, but sometimes develops in boys with X-linked Alport syndrome. Proteinuria is usually progressive. Significant proteinuria in female patients is rare.

Hypertension is more commonly present in male patients with XLAS and in patients of both sexes with ARAS. The frequency and severity of hypertension increases with age and as renal failure progresses.

Sensorineural hearing loss (hearing impairment) is a characteristic manifestation of Alport syndrome, which is observed quite often, but not always. There are entire families with Alport syndrome who suffer from severe nephropathy but have normal hearing. Hearing impairment is never detected at birth. Bilateral high-frequency sensorineural hearing loss usually presents in the first years of life or early adolescence. At an early stage of the disease, hearing impairment is determined only by audiometry.

As it progresses, the hearing loss extends to low frequencies, including human speech. After the onset of hearing loss, kidney involvement should be expected. American scientists claim that with X-linked Alport syndrome, 50% of men suffer from sensorineural hearing loss by the age of 25, and by the age of 40 - about 90%.

Anterior lenticonus (protrusion of the central part of the lens of the eye forward) occurs in 25% of patients with XLAS. Lenticonus is not present at birth, but over the years it leads to a progressive deterioration of vision, which forces patients to change their glasses frequently. The condition is not accompanied by eye pain, redness, or impaired color vision.

Retinopathy is the most common manifestation of Alport's syndrome on the part of the organ of vision, affecting 85% of men with an X-linked form of the disease. The onset of retinopathy usually precedes kidney failure.

Posterior polymorphic corneal dystrophy is a rare condition in Alport syndrome. Most have no complaints. Mutation L1649R in the collagen gene COL4A5 can also cause retinal thinning, which is associated with X-linked Alport syndrome.

Diffuse leiomyomatosis of the esophagus and bronchial tree is another rare condition seen in some families with Alport syndrome. Symptoms appear in late childhood and include swallowing disorders (dysphagia), vomiting, epigastric and retrosternal pain, frequent bronchitis, shortness of breath, cough. Leiomyomatosis is confirmed by computed tomography or MRI.

Autosomal recessive form of Alport syndrome

ARAS accounts for only 10-15% of cases. This form occurs in children whose parents are carriers of one of the affected genes, the combination of which causes the disease in the child. The parents themselves are asymptomatic or have minor manifestations, and the children are severely ill - their symptoms resemble XLAS.

Autosomal dominant form of Alport syndrome

ADAS is the rarest form of the syndrome, affecting generation after generation, with males and females equally severely affected. Renal manifestations and deafness resemble XLAS, but renal failure may occur later in life. Clinical manifestations of ADAS are complemented by a tendency to bleeding, macrothrombocytopenia, Epstein's syndrome, and the presence of neutrophilic inclusions in the blood.

Diagnosis of Alport's syndrome

Laboratory tests. Urinalysis: Patients with Alport's syndrome most often have blood in the urine (hematuria) as well as a high protein content (proteinuria). Blood tests show kidney failure.
tissue biopsy. Kidney tissue obtained from a biopsy is examined using electron microscopy for the presence of ultrastructural abnormalities. A skin biopsy is less invasive and US experts recommend doing it first.
Genetic analysis. In the diagnosis of Alport syndrome, if doubts remain after a kidney biopsy, genetic analysis is used to obtain a definitive answer. Mutations of type IV collagen synthesis genes are determined.
Audiometry. All children with a family history suggestive of Alport syndrome should have high-frequency audiometry to confirm sensorineural hearing loss. Periodic monitoring is recommended.
Eye examination. Examination by an ophthalmologist is very important for early detection and monitoring of anterior lenticonus and other abnormalities.
Ultrasound of the kidneys. In advanced stages of Alport's syndrome, ultrasound of the kidneys helps to identify structural abnormalities.

British experts, based on new data (2011) on genetic mutations in patients with X-linked Alport syndrome, recommend testing for COL4A5 gene mutation if the patient meets at least two diagnostic criteria according to Gregory, and analysis of COL4A3 and COL4A4 if the COL4A5 mutation is not autosomal inheritance is found or suspected.

Alport Syndrome Treatment

Alport's syndrome is currently incurable. Studies have shown that ACE inhibitors can reduce proteinuria and slow the progression of kidney failure. Thus, the use of ACE inhibitors is reasonable in patients with proteinuria, regardless of the presence of hypertension. The same applies to ATII receptor antagonists. Both classes of drugs appear to help reduce proteinuria by lowering intraglomerular pressure. Moreover, inhibition of angiotensin-II, the growth factor responsible for glomerular sclerosis, could theoretically slow down sclerosis.

Some researchers suggest that ciclosporin may reduce proteinuria and stabilize renal function in patients with Alport syndrome (studies have been small). But reports say that patients' response to ciclosporin is highly variable, and sometimes the drug can precipitate interstitial fibrosis.

In renal failure, standard therapy includes erythropoietin to treat chronic anemia, drugs to control osteodystrophy, correction of acidosis, and antihypertensive therapy to control blood pressure. Hemodialysis and peritoneal dialysis are used. Kidney transplantation is not contraindicated for patients with Alport's syndrome: transplantation experience in the USA has shown good results.

Gene therapy for various forms of Alport syndrome is a promising treatment option, which is currently being actively studied by Western medical laboratories.

The true causes of the disease

The true causes of alport syndrome are still not fully understood by scientists. In our body there is a gene whose functional responsibility is the exchange of protein in the tissues of the kidneys. So the mutation of this gene is the most likely cause of the onset of the disease.

Now consider the provoking factors that can contribute to the onset of the disease. These include:

• • severe infectious processes;
  • vaccinations;
  • strong physical activity.

As can be seen from numerous cases of medical practice, sometimes a common acute respiratory viral infection can contribute to the development of alport syndrome. It is in view of such high risks of morbidity that children who have a burdened heredity should undergo regular diagnostic examinations more often.

For the first time this disease was registered at the beginning of the last century. The doctor observed a family in which hematuria was observed for several generations. Later, a link was seen between hematuria and hearing loss, as well as eye damage. Later, when medicine improved, doctors more deeply investigated the genetic nature of this syndrome.

In most cases, its "owners" have relatives with kidney pathologies and other signs of this syndrome. Related marriages also play a role, as a result of which the child has an increased likelihood of receiving the same genes. Patients with Alport's syndrome show changes in the immune system.

Symptoms

Hereditary nephritis has a pronounced clinical symptomatology. If we talk about the initial stages of the pathological process, then it manifests itself as follows:

• • the appearance of blood in the urine;
  • deterioration of visual function;
  • hearing impairment, up to the development of deafness.

Clinical symptoms will increase as the disease progresses. Over time, signs of intoxication appear, and anemia develops. The general condition and age of the patient affect the severity of the clinical picture.

Other characteristic symptoms of the disease are the following signs:

• • severe headaches;
  • muscle pain;
  • even a little physical activity quickly tires the patient;
  • dizziness;
  • arterial hypertension, which is replaced by a sharp drop in pressure;
  • dyspnea;
  • shallow breathing;
  • tinnitus that becomes permanent.

If we are talking about the chronic form of hereditary nephritis, the clinical picture here will be slightly different, namely:

• • weakness and general malaise;
  • frequent urge to urinate, blood impurities;
  • urination does not bring relief;
  • nausea and vomiting;
  • loss of appetite and, consequently, weight loss;
  • hemorrhage;
  • skin itching;
  • convulsions;
  • pain in the chest;
  • in severe cases, there is confusion and bouts of unconsciousness.

Infectious processes of the respiratory tract, active physical activity, preventive vaccinations - all this can provoke an increase in hematuria. As for the presence of protein in the urine, at first proteinuria is intermittent, and then gradually increases and becomes persistent.

Symptoms of intoxication also increase, hearing loss is especially observed in boys, children get tired quickly, they are worried about severe headaches. Children are significantly behind in physical development.

Kinds

Experts distinguish three types of Alport syndrome:

• • pronounced symptoms and rapid progression of acute renal failure;
  • the disease progresses rapidly, but there is no visual and hearing impairment;
  • benign course of the disease, in which there are no clinical symptoms and progression. In this scenario, the prognosis is favorable. If a woman has an autosomal recessive type of inheritance, then a more severe course of the disease is observed.

Diagnostic examination

If there are suspicions of a hereditary factor in children, you should contact your pediatrician as soon as possible. To clarify the diagnosis, laboratory and instrumental research methods are used. As for laboratory diagnostics, it includes a general blood and urine test, as well as a biochemical study.

If we talk about instrumental diagnostics, then this includes the following:

• • ultrasound examination of the kidneys and adrenal glands;
  • kidney biopsy;
  • kidney radiograph.

Sometimes additional genetic tests may be needed. Patients are assigned a consultation with a nephrologist and additionally - genetics.

The main criteria for a diagnostic examination are:

• • the presence in the family of two people with nephropathy;
  • hematuria is the dominant symptom;
  • hearing loss in one of the family members;
  • the occurrence of chronic renal failure in one of the relatives.

If we talk about differential analysis, then hereditary nephritis is compared with the acquired form of glomerulonephritis, in which hematuria is also observed. What is the difference? Glomerulonephritis has an acute onset and there is a direct relationship with the infection. If hereditary nephritis manifests itself in the form of arterial hypotension, then glomerulonephritis, on the contrary, is expressed in arterial hypertension.

Fighting methods

Treatment for alport syndrome involves a combination of medications and a special diet. It is worth noting that specific drugs that would eliminate this particular genetic disease still do not exist. The focus of drugs used in hereditary nephritis is associated with the normalization of kidney function. Diet food for children is prescribed by a doctor individually. As a rule, such prescriptions must be followed for the rest of your life. Outdoor walks are shown. In extreme cases, the specialist may decide to perform surgery. Usually, the operation is performed at the age of fifteen.

Proper nutrition

Immediately I want to note the foods that need to be excluded from the diet. These include:

• • salty, fatty and smoked foods;
  • spices and spicy food;
  • alcoholic beverages, but sometimes doctors may prescribe red wine for medicinal purposes;
  • products that contain artificial colors.

Food should be fortified and high-calorie, but without a high protein content. Physical activity is excluded. Sports, especially for children, can only take place if they are not prohibited by a doctor.

The food should be complete and contain enough proteins, fats and carbohydrates, while the functional abilities of the kidneys should be taken into account.

Renal failure is one of the most severe complications of Alport syndrome. According to statistics, boys from sixteen to twenty years old suffer from insufficiency. If there is no adequate treatment and the right way of life, then death occurs earlier than at the age of thirty.

In addition, it is important to avoid contact with infectious patients to reduce the risk of developing respiratory diseases. Preventive vaccinations are contraindicated in children with hereditary nephritis, and vaccination can be carried out only according to epidemiological indications.

There is no cure for Alport syndrome. This is a genetic disease that cannot be prevented. If the child has been diagnosed with an ailment, then you should follow the recommendations of the doctor and the right lifestyle.

If we talk about forecasts, then the following criteria are extremely unfavorable:

• • male;
  • the presence of chronic renal failure in family members;
  • acoustic neuritis;
  • the presence of protein in the urine.

Patients are prescribed drugs that affect the improvement of metabolism:

• • vitamin A, E;
  • pyridoxine;
  • cocarboxylase.

Transplantation is the most effective treatment for Alport syndrome. The recurrence of the disease in the graft is not observed, and only in minor cases, the development of nephritis is possible.

So, alport syndrome is a serious illness that requires a timely and competent approach to treatment. There is no prevention of hereditary nephritis, but its course can be alleviated with strict adherence to all medical recommendations.

In the last few centuries, scientific and technological progress has been widely developed, massive factories, factories and enterprises are being created. The release of various toxins into the atmosphere, water bodies and soil often leads to the development of congenital diseases. One of the rare ailments of this kind is Alport's syndrome - a pathology that affects several systems of the human body at once (especially the kidneys and sensory organs suffer). It is quite difficult to fight this form of the disease, and there is also a high probability of its transmission to subsequent generations.

Definition of Alport Syndrome

Alport syndrome is a congenital disease associated with the occurrence of pathological mutations in the body. As a result, the formation of abnormal collagen occurs, which disrupts the functioning of organs or tissues. The source of the mutated gene may be one of the parents of the child (more often the disease is transmitted from the mother). Pathology is extremely rare (less than 15 people per 100,000 population).

The triad typical of Alport syndrome is found in 50% of cases

Since the development of the disease is mainly affected by people of the same kindred group, it can be called hereditary nephritis. It is believed that the likelihood of developing an ailment increases with incest.

What types of pathology exist:

• isolated damage to the renal glomeruli;
• the presence of hearing loss or deafness in combination with kidney damage and visual impairment;
• deafness, myopia, nephritis and external deformities;
• asymptomatic carrier.

Reasons for the development of the disease

At the heart of the formation of all symptomatic manifestations of the disease is a gene mutation. In the human body, a failure occurs at the molecular level, as a result of which the normal assembly and transportation of collagen, a protein that is part of almost all organs and tissues of the human body, is disrupted. The disease is hereditary and can be transmitted to the patient from his ancestors in the following ways:

• autosomal dominant (occurs in a person, even if only 1 of his parents suffered from an illness);
• autosomal recessive (occurs in a child when the mother and father have the same genetic mutations);
• sex-linked (a woman is an asymptomatic carrier, and a man develops the entire clinical picture of the disease).

Exacerbation and manifestation of Alport's syndrome occur when exposed to the following factors:

• transferred ARVI, flu, colds;
• surgical intervention;
• traumatic damage to various organs and tissues;
• stress and mental stress;
• vaccination against infections;
• pregnancy, childbirth, the formation of menstrual function;
• use of drugs, alcohol and nicotine;
• uncontrolled intake of drugs.

Clinical manifestations of Alport syndrome

Symptoms of this disease in 80% of patients appear in the first 10 years of life. When carrying mutant genes, people may not even be aware that they have such an ailment, since its typical picture is completely absent. Due to the different clinical forms of Alport syndrome, it is impossible to clearly distinguish the leading symptom of the disease, several symptoms are observed at once:

1. Reduced vision. The patient notes that in low light, the clarity of the letters disappears, the image begins to blur and get lost. This is directly related to the change in the collagen fibers that make up the lens of the eye. Initially, it is possible to correct this problem with the help of glasses and lenses, but subsequently the patient may need surgery.
2. Hearing loss or complete deafness. Most often, the appearance of this symptom is noticed by friends and relatives: the patient constantly adds sound, cannot perceive whispered speech, he begins to speak louder. Both ears are affected, as a result of which the patient cannot perceive low and high frequencies. Patients may also complain of increasing noise inside the head that interferes with concentration.
3. The appearance in the urine of foreign impurities. When the kidneys are damaged during Alport syndrome, vascular damage develops, resulting in the formation of blood in the urine. First, single erythrocytes are detected, with the progression of the disease, the urine is completely stained, massive clots appear. With an unfavorable course of the disease, a blockage of the ureter or pelvis occurs, as a result of which the passage of urine is disturbed.
4. Pain in the lumbar region. Unpleasant pressing and pulling sensations are aggravated by physical exertion, stress, inflammatory diseases, and taking certain medications. Their occurrence is associated with deformation of the renal substance due to edema.
5. Drops in blood pressure. Patients often complain of shingles headaches that occur after eating salty, fatty foods or alcohol. This symptom is a sign of the development of arterial hypertension that accompanies kidney damage. And also for patients with Alport's syndrome, collapse is typical - relaxation of peripheral vessels, as a result of which pressure drops sharply and the victim loses consciousness.

Various methods of confirming the diagnosis

A patient with a progressive decrease in hearing, vision and problems with the urinary system most often turns to a therapist. In the presence of all three main signs of the disease, it is not difficult to immediately make a diagnosis. However, in the absence of one or more of them, it is much harder to decide. Alport's syndrome is differentiated from:

• sensorineural hearing loss;
• labyrinth deafness;
• myopia;
• cataract;
• pyelonephritis;
• glomerulonephritis;
• malignant or benign kidney tumor.

The following methods are used to confirm the diagnosis:

• a general urine test - the appearance of protein, red blood cells and a change in the turbidity of the urine make it possible to suspect kidney problems;
• ultrasound diagnostics reveals pathological edema of the glomeruli and a violation of their structure;
• a progressive decrease in the frequency of hearing is recorded using tympanometry (the elasticity of the eardrum is determined);
• myopia is detected by an ophthalmologist using special tables and apparatus (a decrease in visual acuity is a clear symptom of the disease);
• molecular genetic typing of biological material (mutations are detected in the human genome responsible for the formation of pathological collagen).

Alport syndrome is a rather rare disease that is difficult for a young doctor to suspect. One of my patients went through a long journey through various authorities before being diagnosed. At the age of 6, he was diagnosed with progressive hearing loss, after which the child was sent to an ENT doctor. He confirmed the diagnosis and prescribed a hearing aid for permanent wear. During a vision test before entering grade 1, the baby was found to have severe myopia that could not be corrected with glasses. In adolescence, the boy began to get sick often and constantly experienced kidney problems, which doctors mistakenly took for manifestations of pyelonephritis after the flu or tonsillitis. For several months, the patient was treated with antibiotics, and his condition steadily worsened. Only after that, the doctors decided to conduct a genetic study, which revealed the presence of a collagen protein mutation. The boy was selected a suitable course of therapy, after which he felt better and the opportunity to perform a kidney transplant operation appeared.

How is Alport syndrome treated?

Tactics after confirming the diagnosis of the disease directly depends on the severity of the patient's condition. If he does not have visible clinical manifestations of renal failure and intoxication of the body, treatment is carried out at home or in a day hospital, where a person must regularly come for pharmaceuticals. With a more severe course of the disease, hospitalization in the department of nephrology or urology is indicated. Drug therapy is aimed at eliminating the main symptoms of Alport syndrome, as well as protecting against damage to the kidney tissue. In the absence of the effect of conservative treatment, hemodialysis is prescribed, and after it - a kidney transplant operation. The patient must always observe the ward regimen and adhere to the diet.

The main goals of therapy for Alport syndrome:

• prevention of progression of renal failure;
• normalization of water-salt balance;
• protection against microbial infection;
• strengthening immunity;
• removal of harmful toxins from the body.

Table: used medications

Photo gallery: means for drug therapy of the disease

Furosemide removes excess fluid from the body
Nimesulide has an analgesic effect Polyoxidonium strengthens the immune system

A patient with kidney disease must constantly follow a diet. With Alport syndrome, the normal absorption of nutrients is disrupted, and various toxins are not removed from the body. To combat the symptoms of the disease, a huge amount of energy is spent, which must be restored with the help of food. The balance of proteins, fats and carbohydrates should be 4:1:1. It is necessary to add more vitamins of groups B, C and A to the diet, as well as trace elements sodium, potassium, calcium and magnesium. It is recommended to cook only with fresh produce purchased from a farmers' market or from private sellers to avoid preservatives and harmful additives.

Patients with Alport syndrome need to regularly monitor the amount of water consumed. More than 2 liters during the day create an extra burden on the kidneys.

Approximate food menu for patients:

1. Breakfast. Omelet with goat cheese and greens, some toast with butter and ham. It is recommended to replace coffee with red tea so as not to provoke an increase in blood pressure. As an alternative to scrambled eggs, various cereals with milk or cottage cheese with fruit can be used.
2. Dinner. Soup cooked on lean beef, chicken or turkey (borscht, pea, cabbage soup, pickle, kharcho), as well as sea or sauerkraut salad. If necessary, you can eat a few slices of black bread with garlic or onions to strengthen immunity.
3. Dinner. Lean cutlets, boiled chicken or fish with a minimum amount of salt. For garnish, you can use durum pasta, stewed vegetables (it is recommended to limit the use of potatoes), rice, buckwheat, lentils, chickpeas, beans.

Photo gallery: healthy food

Curd is the best source of calcium Vegetables and fruits are rich in vitamins Cereals - a source of slow carbohydrates

Physiotherapy techniques to combat the symptoms of the disease

At the recovery stage, it is necessary to strengthen the patient's body and protect it from the development of secondary complications. Physiotherapy procedures, which are based on the application of physical phenomena, perfectly cope with these tasks. The course of treatment is selected by a nephrologist based on data on the course of the disease. With an exacerbation of Alport's syndrome, it is recommended to cancel some procedures, as they will cause more harm to the body than good.

Physiotherapeutic methods for the treatment of pathology:

1. UHF therapy is based on the use of high frequency electric fields. This method helps to get rid of discomfort in the lumbar region, and also relaxes spasmodic muscles.
2. Massage is prescribed in the absence of data on the prolapse of the kidneys. Acupressure on soft tissues improves blood circulation and lymph outflow, which protects the body from the addition of unwanted complications in the form of venous stasis.
3. laser therapy. Directed beams reduce the intensity of inflammation, and also prevent the formation of pathological growths of connective tissue (adhesions).
4. The use of ultrasound promotes faster regeneration of soft tissues and ensures the healing of minor injuries.

Photo gallery: physiotherapy to combat the disease

The use of a laser protects against the development of adhesions
UHF therapy effectively copes with the symptoms of the disease Ultrasound therapy stimulates regeneration

Surgical techniques to eliminate the consequences of the disease

In Alport's syndrome, kidney tissue is affected (especially the tubular system). The organ loses its ability to perform its usual functions, as a result of which it needs to be replaced. The selection of a donor is carried out on the basis of many criteria (the next of kin are not suitable due to the likelihood of a latent form of the disease) and takes up to several years. Transplantation is performed in patients from 5–6 years of age.

The operation goes through the following steps:

1. Treatment of the surgical field. The lumbar region is covered with sterile wipes and wiped with alcohol and iodine.
2. The doctor makes an incision, successively pushing the skin, fatty tissue and muscle bundles apart. The damaged kidney and its pedicle, including vessels, ureter and nerve bundles, are removed from the wound. In parallel with this, other medical workers prepare the graft.
3. The new kidney is placed slightly higher than the previous one, after which it is sutured and fixed to the surrounding tissues. The changed old organ is not removed so that it also continues to perform at least part of its functions.
4. Consistent connection of skin, fatty tissue and muscle bundles. A rubber tube remains in the wound area - drainage, through which pathological contents (pus, blood) flow. The operated patient is transferred to the intensive care unit for observation.

Remember that a donor kidney transplant will not help you get rid of Alport syndrome. In my practice, I met a patient who, after the operation, drastically changed his usual way of life, began to actively drink alcohol and smoke several cigarettes during the day, and stopped taking the necessary medications. This led to a sharp deterioration in his condition, the man was hospitalized in the intensive care unit, as the transplanted kidney began to be rejected. At the cost of incredible efforts, the doctors managed to leave the transplant and prevent its infection. That is why even after the operation, it is necessary to monitor your health and take medication.

Hemodialysis for Alport's syndrome

With a long-term violation of kidney function, toxins accumulate in the body, which are difficult to remove without outside intervention. Hemodialysis is used to protect the brain, nervous system, and other important organs from damage. This procedure is aimed at extrarenal blood purification from harmful impurities (chemical elements, decay products of harmful substances, various microbes) and is indicated for all patients with moderate Alport syndrome. Hemodialysis is prescribed in the following situations:

• a threatening increase in the level of creatinine and urea;
• severe impairment of kidney function;
• failure of one of the organs.

The treatment consists in the mechanical purification of the blood

The patient is on a reclining couch, after which special catheters and tubes are inserted into the cubital vein. Through them, blood flows into the apparatus, which passes fluid through elastic membranes. Thus, the bloodstream is cleared of toxins and foreign impurities, since they do not pass through the pores of the filter. Repeat this treatment as needed (at least 1 time in 6 months).

During hemodialysis, the patient is provided with a certificate or sick leave for all the hours that the procedure requires. Patients practically do not experience discomfort and can safely go about their business. Patients in my department prefer to spend time reading books, watching movies or series, word games. This helps to create a comfortable psychological environment.

Predictions and undesirable consequences of the disease

Alport syndrome is an incurable hereditary pathology that is passed on to the next generation with the genes of one or both parents. A complete cure cannot be achieved even after a kidney transplant operation. All therapy is aimed at maintaining the patient's well-being at the desired level and protecting against the development of complications. The life expectancy of patients with this diagnosis is reduced by 10–15 years. The likelihood of developing undesirable consequences is influenced by the age of the patient, the presence of other acute or chronic ailments, injuries and infections, as well as lifestyle and compliance with medical recommendations.

When a disease is detected in children, an individual program of training and monitoring of health indicators is created for each baby, which makes it possible to avoid undesirable consequences.

While working in the Department of Nephrology, I had the opportunity to encounter a man aged 65 who was diagnosed with Alport syndrome in childhood. The patient did not have any characteristic external changes, and all tests were extremely good. During the survey, it was found that the patient leads a predominantly healthy lifestyle, regularly vaccinated against influenza, eats food in accordance with the diet, engages in light physical activity, does not smoke or drink alcoholic beverages. This attitude of the man to treatment allowed him to avoid a kidney transplant operation, as well as to refuse from hemodialysis for a long time.

Possible complications and undesirable consequences that may occur in patients with Alport syndrome:

• chronic or acute renal failure;
• creation of conditions for the accession of a secondary infection;
• immunodeficiency states;
• destruction of one or both kidneys;
• accumulation in the body of toxic substances that are not excreted in the urine;
• social maladaptation;
• progressive deterioration of hearing and vision;
• increased risk of developing malignant neoplasms;
• anemia - a decrease in the level of hemoglobin and red blood cells in the blood;
• inflammatory diseases of the kidneys;
• disorders of mental and physical development (in children).

Features of the clinical picture and treatment of Alport syndrome in children

You can suspect the presence of a pathology in a baby immediately after his birth. Children have characteristic changes and deformities of the facial skull in the form of a splitting of the upper lip (cleft lip) and a funnel-shaped hard palate (cleft palate), increased head size, as well as a typical facial expression with a wandering look. Other mutations can manifest as hearing and visual impairment. Such a child does not even react to loud sounds and sudden movements of the environment, which is found even in the maternity hospital.

To eliminate external defects, small patients undergo plastic surgery. I happened to participate in the suturing of the upper lip of a child with such a problem. After surgery, a small scar remains, which fades over time and becomes almost invisible. Operations are performed within a few weeks after the birth of the child, which reduces the risk of secondary complications.

To prevent damage to the kidney tissue, small patients are prescribed a special diet. Newborns and infants are breastfed or receive a mixture that is maximally adapted to the composition of human milk. This eliminates the risk of developing an immune deficiency. The main means for the treatment of symptomatic signs of the disease are introduced at 5–7 years of age (earlier - as needed) and practically do not differ from the treatment that an adult receives. For the adaptation of blind and deaf children in society, hearing aids are used, corrective operations. For the first few years, the child must attend special schools or additionally study with a specialist in order to catch up with peers.

Photo gallery: what children with Alport syndrome look like

A change in the shape of the skull during the disease occurs in 40% of cases Puffiness of the face is a result of improper functioning of the kidneys. External defects help to immediately suspect the presence of an ailment

Features of the development of the disease in girls and the impact on reproductive function

In female patients, there are not always clear signs of Alport syndrome. Many girls learn about the carriage of such a pathology only after the birth of a sick baby. In more severe cases, the disease is activated during puberty under the influence of hormonal changes in the body (during menstruation) or after the first sexual experience.

If the patient's condition is stable, and there are no other contraindications (damage to a single kidney, recent surgery), you can have a baby.

In my practice, there was a patient in whom Alport's syndrome appeared every 3 generations. In this patient, the pathology was dormant for a long time, but became more active after the stress. The woman noted that her great-grandmother and sister also suffered from this form of the disease. Doctors calculated that the likelihood of such a disease appearing in subsequent generations is extremely high.

Patients with a severe form of Alport's syndrome experience certain difficulties in conceiving and bearing a child. This may be due both to abnormalities in the structure of the reproductive organs, and to disruption of the endocrine system. During the period of growth and development of the fetus, the mother's body produces 2 times more fluid, as a result of which the load on the kidneys increases significantly. Due to nephritic changes of an inflammatory nature, the body cannot cope with an increase in the volume of circulating blood, and a woman has miscarriages at various times.

What complications can occur in patients with Alport syndrome during pregnancy:

Hereditary kidney diseases are a group of dangerous pathologies that significantly reduce not only the quality of human life, but also its duration. Currently, the problem of early diagnosis of Alport's syndrome is especially relevant. Almost all patients live in ignorance for many years, until some abrupt factor provokes the development of clinical symptoms of the disease and its complications. That is why it is so important to constantly monitor your health, noting the slightest changes in well-being, as well as regularly consult a doctor to monitor tests.

Hereditary nephritis or Alport syndrome is a genetic disease that is not common. Signs of pathology appear in children from 3 years old until they reach primary school age. The disease is more common in boys. In some cases, it may not be expressed by bright symptoms for a long time, therefore, it is detected when other diseases are suspected during diagnostic studies or medical examinations.

Causes

A genetic change in the gene responsible for the process of collagen biosynthesis is the main prerequisite for the development of Alport's syndrome. A child acquires such a hereditary mutation from his parents: a daughter from her father, and from her mother - both a boy and a girl. A gene can be damaged in a person, while the disease does not always develop, but will be inherited by children.

One of the three genes responsible for the process of biological synthesis of type IV collagen undergoes a change. It is he who enters the structure of the basement membranes located in the kidneys, organs of vision and hearing. Basement membranes are special formations - thin borders by which some tissues of the human body are separated from each other, support and strengthen their structure. If their composition and integrity are violated, dangerous phenomena arise:

• there is an incomplete and poor-quality filtration of toxic and other substances coming from the blood;
• the composition of urine changes, in which there is a significant increase in red blood cells (hematuria or traces of blood in the urine) and unfiltered protein (proteinuria).

Such changes lead to the development of severe renal failure, in some cases to the complete cessation of organ functions and death.

Alport syndrome and its development can provoke some factors:

• severe illnesses caused by bacteria or viruses;
• impact on the body of vaccine components;
• excessive physical loads.

Medical statistics have data that every fifth child with a confirmed diagnosis of hereditary nephritis appears in parents who do not have pathologies associated with kidney function. The cause of Alport's syndrome in such cases is associated with gene mutations of a spontaneous type.

Classification and characteristic features

Genetic nephritis has two classifications. Experts distinguish its types depending on the type of inheritance of the pathology and the characteristics of the development of the disease.

There are three types of hereditary nephritis:

• classic or X-linked dominant - is the most common, is confirmed in 80% of patients;
• autosomal recessive - no more than 15% of patients are affected;
• autosomal dominant Alport syndrome is extremely rare in medical practice, diagnosed in less than 5% of patients.

A nephrologist classifies the diagnosis of Alport syndrome depending on the characteristics of the manifestations of the pathology:

• changes in kidney function, suggesting the presence of hematuria with simultaneous visual and hearing impairments;
• nephritis with signs of hematuria, developing without a decrease in the functions of the organs of vision and hearing;
• familial hematuria of a benign nature, without signs of chronic renal failure.

Since the cause of Alport's syndrome is a violation of the production of the main element of connective tissues - collagen, its main symptoms are associated with the processes of changing the structure of the basement membranes. Their structure is disturbed in important parts of the human body:

• renal glomeruli;
• inner ear;
• organs of vision.

The most common and primary symptom is the presence of hematuria. Blood in the urine may be visible or detected in laboratory tests. The appearance of signs of hearing loss, complete unilateral deafness (in some cases), visual impairment increase the suspicion of the possible development of Alport's syndrome. In patients, the presence of protein in the urine may be confirmed.

When a child develops hereditary nephritis, his condition indicates intoxication of the body, which can be determined by the following symptoms:

• decrease in hemoglobin level;
• dizziness, tinnitus;
• frequent occurrence and repetition of muscle and headache;
• change in breathing that becomes shallow;
• the presence of shortness of breath;
• the value of blood pressure is not stable, it can both increase and decrease;
• insomnia or excessive sleepiness.

In cases of development of hereditary nephritis in a chronic form, the patient's condition is aggravated by the manifestation of additional signs:

• problems with the process of urination, increased frequency of visits to the toilet;
• the presence of blood in the urine;
• signs of general malaise, severe weakness, loss of appetite;
• the presence of muscle cramps;
• the appearance of bruising, skin itching;
• noticeable pain in the chest area;
• change of consciousness, sometimes to unconsciousness.

Pathology can proceed with external signs. A child may have a special structure of the auricles and palate, fusion of fingers or the presence of additional ones, a pronounced fold at the inner corner of the eye.

Diagnostics

The diagnosis of hereditary nephritis is helped by several studies, the collection and analysis of anamnesis. It is the genetic nature of the disease that involves the study of the health characteristics of the parents, grandparents of the baby. An assessment of indicators is necessary, the presence of three of them allows diagnosing the syndrome:

• signs of hematuria;
• kidney pathology, renal failure, including death;
• diseases of the organs of vision and hearing of a congenital nature;
• progressive deterioration in the quality of visual and auditory perception in a child;
• the presence of changes in the structure of the basement membrane (performed with a biopsy of the renal tissue).

To assess the patient's condition and the development of the pathological process, the doctor prescribes studies:

• analysis for Alport syndrome (involves the study of blood and urine);
• ultrasound examination of the kidneys, adrenal glands;
• conducting radiography of the organ;
• tissue biopsy;
• DNA test to determine the carrier of the mutant gene.

The patient requires additional visits to highly specialized doctors - a nephrologist, geneticist, oculist, otolaryngologist.

Necessary treatment

The treatment of Alport syndrome consists in normalizing the work of the kidneys, since there are no special, specific medicines to get rid of all the symptoms of the pathology.

The doctor prescribes treatment that reduces the risk of progression of the syndrome:

• drugs that correct the manifestations of renal failure, the level of protein in the urine;
• diuretics;
• means that normalize the metabolism in the body, restore the balance of minerals and vitamins;
• drugs for the prevention of anemia.

In severe renal failure, it is indicated using the hemodialysis procedure. In severe cases of the development of hereditary nephritis, it is necessary to replace the affected organ with a donor one. Kidney transplantation can be performed on patients over the age of 15 years.

Risk of Complications

The development of renal failure is a dangerous complication of Alport syndrome. If the disease is not diagnosed in time and treatment is not started, the person will not live long. Death with a high degree of probability will overtake him before reaching the age of thirty.

Diet food

Great importance in the diagnosis of hereditary nephritis is given to the transition to a special diet. The diet for Alport syndrome involves the complete exclusion of "wrong" foods:

• containing preservatives and non-natural food additives;
• spicy and salty dishes;
• fatty ingredients;
• high in protein;
• any alcoholic beverages.

The diet uses products individually recommended by the doctor. Their list is formed taking into account the functional abilities of the kidneys of each patient. It is proposed to introduce into the diet components that provide the patient with the necessary energy, vitamins and microelements, as well as having sufficient calories - veal, lean beef, poultry, fish, fruits and vegetables.

Forecast and prevention

Depending on the classification of hereditary nephritis, the prognosis can vary significantly. Patients who progress to chronic renal failure, observed with a high degree of proteinuria, are at the highest risk of possible death. Boys are more likely to be on this list. In most cases, patients need a kidney transplant.

Alport syndrome (SA) is an inherited type IV collagen disorder characterized by a combination of progressive hematuric nephritis with ultrastructural changes and sensorineural hearing loss. Visual disturbances are also common in this syndrome. Microhematuria, detected in the early stages of life, is a constant characteristic sign of the disease.

Recurrent episodes of gross hematuria occur in about 60% of patients under 16 years of age, but are rare in adults. Over time, it joins and the disease progresses with age, depending on the gender of the patient and the type of inheritance of the disease. is a late sign.

Bilateral sensorineural hearing loss affecting high and medium frequency hearing is progressive in children but may become apparent later. There are reports of several types of visual disturbances, also progressive with age. Anterior lenticonus is a cone-shaped protrusion of the anterior part of the lens. Yellowish spots appear on the retina of the eye, which are asymptomatic. Both types of lesions are specific and occur in about a third of patients. There are also reports of recurrent corneal erosions in SA patients.

Morphology

Under light microscopy, kidney tissue obtained in the early stages of AS appears normal. Focal and segmental thickening of the capillary walls of the glomeruli, better detected by silver staining, become visible with the progression of the disease. They are associated with nonspecific tubular lesions and interstitial fibrosis. Standard immunofluorescence is usually negative. However, faint and/or focal grade G and M deposits and/or complement fraction C3 may be detected. The main damage is detected by the ultrastructural method. They are characterized by thickening (up to 800-1200nm) with splitting and fragmentation of the lamina densa into several fibers forming a network like a basket. Changes can be fragmentary (heterogeneous), alternating with areas of normal or reduced thickness. In general, the most prominent feature in children is the uneven alternation of very thick and very thin areas of the GBM. Diffuse thinning of the GBM is found in about 20% of patients with SA.

At the genetic level, AS is a heterogeneous disease: mutations in COL4A5 on the X chromosome are associated with X-linked AS, while mutations in COL4A3 or COL4A4 on chromosome 2 are associated with autosomal forms of the disease.

X-linked Alport syndrome.

clinical symptoms.

The X-linked variant is the most common form of SA, characterized by a more severe course of the disease in male patients than in female patients, and the absence of transmission through the male line. Availability hematuria is a necessary criterion for diagnosis. gradually increases with age and can subsequently lead to the development of nephrotic syndrome. In all male patients, the disease progresses to end-stage kidney disease. There are two types of AS - juvenile, in which ESRD develops around the age of 20 in men with maternal transmission, and adult, characterized by a more variable course and development of ESRD around the age of 40. In heterozygous females, hematuria is found only in adulthood. It is absent in less than 10% of women (carriers). The risk of developing ESRD in women under the age of 40 is about 10-12% (against 90% in men), but increases after age 60. Most heterozygotes never develop ESRD. Bilateral sensorineural hearing loss progresses in most male patients and in some females. Changes in the organ of vision, anterior lenticonus and/or perimacular spots are observed in 1/3 of patients. In families with AS, women may have diffuse esophageal leiomyomatosis, which also includes lesions of the tracheobronchial tree and genital tract of women and sometimes congenital cataracts.

Molecular genetics made it possible to establish the features of mutations in the COL4A5 gene. They cause differences in clinical manifestations, course and prognosis.

Autosomal recessive Alport syndrome

Alport syndrome is inherited in an autosomal recessive manner in about 15% of affected families in Europe. This type of inheritance is more common in countries with higher levels of consanguineous marriages. Clinical symptoms and ultrastructural changes are identical to those observed in X-linked SA. However, some signs clearly indicate recessive inheritance: consanguineous marriages, severe disease in female patients, absence of severe disease in parents, microhematuria in the father. The disease, as a rule, progresses early to ESRD, almost always there are hearing impairments, not always - damage to the organ of vision.

Among heterozygotes, persistent or intermittent microhematuria is noted.

Autosomal dominant Alport syndrome

Autosomal dominant inheritance, characterized by transmission through the male line, is rare. The clinical phenotype is the same for men and women. The course is milder than in the X-linked form, with late and inconsistent progression to the development of ESRD and hearing loss. Heterozygous mutations in the COL4A3 or COL4A4 genes have been identified in some families.

Diagnosis and treatment of Alport's syndrome. Diagnosis of AS and determination of the type of inheritance are important for therapeutic management, prognosis, and genetic counseling of patients and their families. The issue is easily resolved if hematuria is combined with deafness or eye damage and if the hereditary history is sufficiently informative to establish the type of inheritance. Each incidentally discovered hematuria requires examination of other family members. The early onset of hematuria and the identification of sensorineural hearing loss, lenticonus, or maculopathy on careful examination may suggest SA, but the mode of inheritance remains uncertain. Determination of mutations in the COL4A5, COL4A3, or COL4A4 genes is critical for diagnosing the disease, but molecular analysis is a costly and time-consuming procedure due to the large size of the type IV collagen gene and the wide variety of mutations.

It is important to differentiate Alport syndrome from thin basement membrane disease (TBM) early. This is best done on the basis of family history: the presence in the family of adult men over 35 years of age with hematuria and intact renal function with a high probability allows us to make a diagnosis of TBM.

In the absence of hearing loss, diagnosis is quite difficult: if you do a kidney biopsy too early (before 6 years), you can not see the changes characteristic of Alport syndrome that will develop later, and electron microscopy is not available everywhere. In this regard, it is promising to introduce an immunohistochemical method for determining the expression of various type IV collagen chains in the renal tissue or in the skin.

Sporadic hematuria with proteinuria, detected in the absence of extrarenal manifestations, is the reason for a renal biopsy to exclude other hematuric glomerulopathies (IgA nephropathy, etc.). Progression to end-stage kidney disease is inevitable in X-linked SA in men and in all patients with autosomal recessive SA. To date, there is no specific treatment. The main treatment is blockade of the renin-angiotensin system to reduce and possibly slow down the progression. Kidney transplantation leads to satisfactory results, however, about 2.5% of all patients with SA develop anti-GBM due to the formation of a “different” donor GBM, which leads to graft rejection.

Alport syndrome is a hereditary abnormality that manifests itself in the early onset of kidney failure, hearing loss and visual impairment.

This syndrome is a hereditary form of inflammation of the kidneys - jade. It's connected with a mutation in a protein gene, called collagen.

The disorder is rarely seen. More often it occurs at the stronger sex.

Women can pass on the gene for the disorder to their children, even if they don't have symptoms.

To risk factors relate:

• Severe kidney disease in male relatives;
• family history of the disorder;
• Hearing loss up to 30.

Clinical picture

Symptoms may already be present in the first year of life crumbs, but most often manifested at 3–5 years old.

In most children, the predisposing condition is past infection. Due to the lack of manifestation, the disease may be detected by chance according to the results of urine tests.

This type of nephritis in children can take the form of hematuric glomerulonephritis or pyelonephritis.

initial stage deviations are inherent no complaints. During normal kidney function, only changes in urine: erythrocytes, leukocytes, protein appear.

Development of the disorder associated with nephrotic syndrome and high blood pressure. Patients have the following symptoms:

• weakness,
• pain in the head,
• visual impairment, hearing loss,
• pressure drop,
• skin pallor,
• lethargy.

The difference between Alport's syndrome in children and other forms of nephritis is damage to the auditory nerve.

The difficulty is that it can be identified only after audiometry, which is carried out after 7 years. Only 20% of children have visual impairments, and thrombocytopenia is observed only in some cases.

Deafness is more often manifested in boys - they also have an increase in pressure and a progressive decrease in kidney function much faster.

By the age of 18 the development of the disease causes a complete set manifestations of renal failure:

• skin pallor,
• dry mouth
• nausea,
• trembling of the hands and fingers,
• a decrease in the volume of excreted urine or its complete absence,
• sometimes there is an ache in the muscles and joints.

Without timely replacement therapy or transplant of a diseased kidney human lifespan will not exceed 40 years.

Syndrome forms:

autosomal recessive

With this type of inheritance, the mutated gene appears only when one recessive gene is received from the father, and the second from the mother.

Risk the appearance of an unhealthy baby is 25%.

Sick boys and girls are born equally often.

Parents of sick babies may appear healthy but are carriers of an unhealthy gene.

autosomal dominant

Dominant inheritance, based on the X chromosome, is that the action of the dominant unhealthy gene is manifested regardless of gender.

More hard the disorder resolves in boys.

One of the child's parents is certainly not healthy. Among the children of a man, sons are healthy, and daughters are sick. Women pass on the mutated gene to 50% of their sons and daughters.

How to diagnose a disease?

Syndrome is suspected based on pedigree by the presence of the disorder in other relatives. For the diagnosis of the disease, it is necessary to the presence of three out of five indicators:

1. Hematuria or death from kidney failure in the family;
2. Hematuria or proteinuria in relatives;
3. Detection of changes in organ biopsy;
4. hearing loss;
5. congenital visual impairment.

Diagnostics violations are carried out in the following ways:

• Collection and study of anamnesis;
• Physical method;
• Laboratory tests;
• ultrasound study,
• Computed or magnetic tomography;
• Scintigraphy;
• Biopsy.

The distinguishing diagnosis of the disorder is distinction between nephritis and nephropathy.

Is it possible to treat Alport syndrome?

There is no specific treatment. Great importance is attached pressure control and dietary protein restriction when kidney function starts to decline.

As XHH progresses, patients are given hemodialysis treatment.

People with the syndrome are shown to have a kidney transplant, although in some situations, Goodpasture's syndrome may occur after a transplant.

Therefore, the selection of donors must be carried out very carefully.

In the absence of specific treatment, the main goal is to slow the development of kidney failure.

children prohibited physical activity, a balanced diet is prescribed.

Special attention is paid to treatment of infectious foci.

The use of hormonal agents and cytostatics does not cause significant improvement. The main treatment remains organ transplant.

Poor prognosis of the course of the disease, which is characterized by the rapid development of terminal renal failure, is likely in the presence of such indicators:

• Male;
• High protein content in urine;
• Early appearance of kidney disorders in relatives;
• Hearing loss.

Upon detection hematuria without proteinuria and hearing loss the prognosis for the course of the disorder is favorable, failure does not occur.

The course of the syndrome is progressive and not progressive, the prognosis is positive in women without hearing changes.

Each patient has his own degree of development of the process in the kidneys.

In 50% of boys, the last stage of kidney failure occurs by the age of 30, and sometimes even by 20 years. In others, the process develops more slowly, but eventually causes a violation of the kidneys.

Girls the disorder progresses more slowly and does not affect life expectancy, even with persistent microhematuria.

Dialysis and organ transplant favor a more positive prognosis.

Video: What you need to know about hereditary diseases

Useful information about hereditary diseases, which will help to avoid the development of many diseases in the unborn child. If you take into account these tips, then the likelihood of having a child with hereditary abnormalities will decrease significantly.

The kidney is a paired organ that performs the function of urination, regulation of blood pressure, mineral metabolism and hematopoiesis.

The laying of the kidneys in the fetus occurs already at 4-5 weeks of pregnancy.

In the presence of a defect in the gene responsible for the synthesis of type 4 collagen, the vascular system of the kidneys, the lens capsule, and the organ of Corti (located in the inner ear) suffer.

This hereditary disease is called Alport syndrome.

Causes of hereditary disease in children

Alport syndrome is also called hereditary inflammation of the kidneys. It occurs in both boys and girls. Pathology is detected during preventive examinations.

The disease is caused by a genetic defect in protein structure. Provoking factors that lead to gene mutation include:

1. Transferred infectious disease of the mother during pregnancy. The infection is especially dangerous in the first trimester, when the organs and tissues of the fetus are laid.
2. Vaccination given to a pregnant woman.
3. Excessive physical activity and emotional stress that constantly accompany the expectant mother.

Types of the syndrome

The following genetic forms of Alport syndrome are distinguished:

• X-linked dominant, or classical (eighty percent with SA);
• autosomal recessive (fifteen percent of patients);
• autosomal dominant (five percent with SA).

Clinical classification is based on the manifestations of this hereditary pathology:

1. Combined damage to the kidneys (nephritis and), eyes, inner ear. Corresponds to the X-dominant form of Alport's syndrome.
2. Kidney damage (accompanied by hematuria) without structural disturbances in the sense organs. This is how the autosomal recessive form of the disease manifests itself.
3. Familial hematuria, which is benign.

In the first two cases, renal failure develops. In the third case, the disease does not affect life expectancy and its quality.

Manifestation of the clinical picture

The doctor and parents may look for the following signs:

• visual impairment;
• hearing loss or deafness;
• developmental delay.

An older child may complain of insomnia, headache, dizziness, fatigue even after little physical activity, which may be a symptom of Alport's syndrome.

The blood pressure in these children is lowered, which is detected during preventive examinations.

Flow stages

The course of the disease depends on its clinical variant:

• with damage to the kidneys, vision and inner ear, the pathology progresses rapidly, leads to the development of renal failure, a further decrease in visual and auditory functions;
• jade, accompanied by (), will also lead to a decrease in excretory over time;
• benign familial hematuria does not lead to life-threatening complications.

Diagnostic Measures

The diagnosis is made on the basis of complaints, objective, laboratory-instrumental, morphological and genetic studies.

Parents pay attention to the change in the color of the child's urine, his fatigue, poor exercise tolerance.

The doctor reveals a decrease in vision and hearing, low blood pressure.

Laboratory research

The child is assigned:

• general analysis of blood and urine;
• biochemical blood test (electrolytes).

In the general blood test, a decrease in the number of red blood cells and hemoglobin is observed, which indicates anemia.

Anemia is associated with a decrease in the production of erythropoietin in the kidneys. Erythropoietin is a stimulant of blood formation.

In the general analysis of urine, protein (proteinuria) and red blood cells (hematuria) are detected. With the development of kidney failure, the density and amount of daily urine decreases.

The indicators of creatinine and urea reflect the excretory ability of the organ. In the presence of a persistent increase in these indicators, the degree of renal failure is set.

Instrumental method

Children undergo ultrasound and radiographic examination of the abdominal cavity, which reveal characteristic changes.

Without fail, the child must undergo audiometry, ophthalmoscopy to detect a decrease in auditory and visual function at an early stage.

Morphological check

It is most valuable in the diagnosis of Alport's syndrome. A biopsy is an intravital examination of tissues. The morphologist describes the structural features of the cortical and medulla of the kidneys, as well as the vascular network of the organ.

genetic recognition

Expensive diagnostic method. Allows you to identify a defective gene that is responsible for the synthesis of a pathological protein.

Who to contact

When the first signs of the disease appear (blood in the urine, decreased hearing and vision in a child), you should contact your pediatrician.

The pediatrician will prescribe additional examination methods, after which you may need a consultation, an ophthalmologist, an ENT specialist and a geneticist.

Therapy Methods

Treatment of Alport's syndrome includes diet, medication, timely sanitation of foci of infection.

Vaccinations for children are contraindicated, vaccination is possible only if there are strict indications.

At the moment, there are no pharmacological drugs that would affect the genetic defect.

Widely used metabolic drugs that allow you to increase. These include cocarboxylase, vitamins A, E, B6. When protein appears in the urine, nephroprotectors (drugs that protect the kidneys) are prescribed.

These include angiotensin-converting enzyme inhibitors (enalapril, lisinopril, ramipril, pyrindopril) and angiotensin receptor blockers (losartan).

The above drugs belong to the group of antihypertensive drugs.

Even with low blood pressure in children, minimal doses of medication should be taken to reduce the rate of progression of kidney failure.

Physical activity

A child with Alport syndrome should refrain from strenuous physical activity. However, he needs daily walks of at least 40 minutes.

This will improve microcirculation in the kidneys, and will also contribute to normal development.

dietary prescriptions

Should be excluded from the diet:

• salty, fatty and smoked foods;
• spices and spicy food;
• Products with a high content of artificial colors.

It is necessary to monitor the amount of protein intake in the body, with the development of renal failure, limit the liquid to one liter, salt to one gram per day.

A sufficient amount of calories, vitamins, macro- and microelements should be supplied with food.

Surgical intervention

On, in which the kidneys cannot cope with the release of toxic metabolic products, a kidney transplant is also performed.

Hemodialysis is performed by the kidney machine. The essence of the procedure is to cleanse the patient's blood from toxic substances, which is vital.

The patient also undergoes a kidney transplant, after which immunosuppressive therapy is prescribed to prevent transplant rejection.

ethnoscience

It is used in conjunction with traditional methods after consultation with the attending physician. The properties of medicinal plants are used to help alleviate the clinical manifestations of the disease.

To improve microcirculation in the kidneys, you can use non-concentrated and.

To increase the glomerular filtration rate will help, juniper fruits, birch buds.

Complications and consequences

The most formidable complication is renal failure. It is evidenced by an increase in such indicators as urea and creatinine, a decrease in the glomerular filtration rate.

At the initial stages of renal failure, diet, the use of drugs is recommended, in the later stages - hemodialysis, etc.

In case of loss of hearing and vision, surgical intervention is performed. Indications for him are set by an ENT and an ophthalmologist.

Forecast and prevention

An unfavorable prognosis is most likely for a male child, as well as in the presence of:

• high concentration of protein in the general analysis of urine;
• early development of renal disorders in close relatives;
• hearing loss.

If isolated hematuria is detected without concomitant proteinuria and hearing loss, the prognosis of the disease is favorable, functional kidney failure rarely develops.

Preventive measures include pregnancy planning (rehabilitation of chronic foci of infection, a woman should avoid excessive physical and emotional stress, be registered in a antenatal clinic in a timely manner, and if indicated, undergo medical genetic counseling).

The child needs to undergo regular preventive examinations at the pediatrician. When the first signs of illness are found, parents should inform the doctor.

Alport syndrome is a severe genetically determined disease of the kidneys, visual and auditory apparatus. With timely diagnosis and adherence to recommendations, it is possible to slow down the rate of development of renal failure, hearing loss.

Alport's syndrome (hereditary nephritis) is rare. This pathology provokes visual impairment and hearing loss. This often leads to the need for a kidney transplant.

This syndrome manifests itself at 3–5 years of age. Hereditary nephritis in children is constantly progressing. In parallel, the child loses hearing and vision, the glomerular apparatus of the kidneys is affected.

Alport syndrome develops due to a mutation in the gene that produces collagen. This type of collagen is involved in the construction of the lens capsule and part of the inner ear. Hence the violations of their function, as well as the functions of the kidneys themselves.

According to the international classification, this pathology refers to congenital anomalies, chromosomal disorders and deformities. It is considered a congenital defect, as several organs and systems suffer at once.

Causes of pathological changes

The main cause of Alport syndrome is gene mutation.

The affected gene is in most cases passed down from one of the parents. If someone in the family suffered from a disease of the urinary system, the likelihood of pathology increases significantly.

In 20% of all cases, spontaneous gene mutation occurs. This means that perfectly healthy parents are guaranteed to have a child with a similar pathology.

Symptoms

Collagen is the most important component of connective tissue. Its deficiency provokes changes in the basement membranes of the renal glomeruli, the eye apparatus and the inner ear. These organs cease to cope with their functions.

Symptoms of this pathology are divided into two main types:

• renal (blood and urine);
• non-renal.

Renal manifestations are also called isolated urinary syndrome.

It does not appear immediately after birth, but closer to 3-5 years. There are cases when the pathology was detected much later at the age of 7–9 years. But there are always tiny drops of blood in the urine. At first, simply patients may not notice them ().

With this pathology, it is important to make the correct diagnosis in time, remove physical activity, provide a strict diet, and regular complex treatment. The right lifestyle plays a big role. Parents should not panic, because modern medicine is able to help even with such a genetic disorder as Alport syndrome. The disease is inherited, so it is necessary to take remedial measures for all family members who have symptoms.

Alport syndrome is a hereditary disease that manifests itself in the early development of renal failure, a decrease in hearing and visual acuity.

The disease is caused by genetic mutations affecting the connective tissue type 4 collagen, which is an integral part of many important structures in the body, including the kidneys, inner ear and eyes.

Alport syndrome is much more difficult to tolerate by males. The fact is that the disease is most often transmitted through a mutated X chromosome. Since girls have two X chromosomes, the healthy one works as a spare and facilitates the course of the disease.

In Alport's syndrome, due to the inability of the kidneys to eliminate toxins, poisoning of the body occurs. Therefore, in females, this pathology can cause infertility. And if pregnancy does occur, the toxins can kill both the baby and the mother. Often, Alport's syndrome manifests itself during pregnancy, even if it did not make itself felt before.

Symptoms of the disease

As Wikipedia says about such an ailment as Alport syndrome, this hereditary disease is characterized by hematuria (blood in the urine), leukocyturia (detection of leukocytes in the urine test), proteinuria (presence of protein in the urine), deafness or hearing loss, sometimes cataracts and the development of kidney failure in adolescence. age. Sometimes kidney damage can occur only after 40-50 years.

The main symptom of the disease is the presence of blood in the urine, which indicates kidney disease. Sometimes it can only be detected microscopically, and in some cases the urine may turn pink, brown or red, especially against the background of connected infections, flu or viruses in the body. With age, in addition to hematuria, protein appears in the urine and the patient has arterial hypertension.

Although Wikipedia describes Alport syndrome as a disease that manifests as cataracts, this is not always the case. Sometimes, abnormal retinal pigmentation can also occur, significantly impairing vision. In addition, the cornea with such a hereditary disease is prone to the development of erosion. Therefore, they need to protect their eyes from getting foreign objects in them.

Alport syndrome also characterizes hearing loss, which usually manifests itself in adolescence. This problem is solved with the help of a hearing aid.

Alport syndrome: treatment and prevention

Alport's syndrome, the treatment of which is mainly symptomatic, involves the mandatory rehabilitation of chronic foci of infections. Patients with this disease are contraindicated to be vaccinated in a quiet time from epidemics. There are also contraindications to taking glucocorticoid drugs. Dialysis is used for kidney failure, and its development after the age of 20 is an indication for kidney transplantation.

Regarding the prevention of pathology, one should beware of urinary tract infections, which accelerate the development of renal failure. Women with Alport syndrome who decide to have a baby should first consult with a geneticist who will help identify the carrier of the mutant gene. Although statistics show that about 20% of families with Alport syndrome do not have relatives suffering from kidney failure. This fact proves that a mutated gene can occur spontaneously.

To protect your descendants from such a hereditary disease as Alport syndrome, it is necessary to avoid consanguineous marriages. And if the carrier of the abnormal gene is identified, in order to eradicate the pathology in the future, you can use donor genetic material and resort to the procedure of insemination or artificial insemination. In each individual case, an individual consultation of specialists is necessary.

Hereditary nephritis (better known name - Alport syndrome) - pathology is quite rare. According to official data, in Russia, for every 100,000 newborn babies, there are 17 with such an anomaly of development. In Europe, 1% of all patients with chronic renal failure (CRF) are people with hereditary nephritis. And 2.3% of kidney transplants are performed on patients with this diagnosis.

Alport Syndrome?

Hereditary nephritis is a progressive kidney disease that often accompanies hearing loss and severe vision problems. In reference books, you can find the definition of Alport syndrome (SA) as a non-immune hereditary form of glomerulopathy, that is, damage to the glomerular apparatus of the kidneys.

Congenital disorder of renal function manifests itself in children as early as 3-5 years old, occurs due to mutations in one of the three genes that are responsible for the production of type IV collagen.

The fourth collagen variety forms the basis of the basement membranes of the renal glomeruli, the cochlear apparatus (part of the inner ear), and the lens capsule. Hence - and simultaneous violations of the kidneys, hearing and vision.

The International Classification of Diseases of the 10th revision (ICD-10), the main regulatory document that systematizes all existing health disorders, classifies a childhood disease as a class of congenital anomalies, deformities, and chromosomal disorders. Since a number of organs suffer from SA, the disease is included in the group of congenital malformations that affect several systems at once. And it is marked with the code Q87.8 - these are "other specified syndromes of congenital anomalies not classified elsewhere."

Causes

The main and only reason why children are born with Alport syndrome is a genetic mutation. One of three genes is damaged - COL4A5, COL4A4, COL4A3. The COL4A5 gene is located on the X chromosome and encodes the a5-chain collagen chain. The "place of residence" of the COL4A3 and COL4A4 genes is the 2nd chromosome. They, respectively, store information about the chains of collagen a3- and a4-.

Most often, the damaged gene is passed on to the baby from the parents. When kidney disease passes along the X chromosome, the mother can become a transmitter of the anomaly to both her son and daughter. The father is only daughters. The likelihood that a baby will be born with kidney damage increases significantly if there are people in the family with diseases of the urinary system (primarily CRF).

But in 20% of cases, children with Alport syndrome are born in families where all relatives have perfectly healthy kidneys. Here we are talking about random, spontaneous genetic mutations.

Symptoms

Congenital hereditary nephritis develops with a lack of collagen, one of the main structural elements of connective tissue. As a result of collagen deficiency, the basement membranes of the renal glomeruli, the inner ear and the eye apparatus become thinner and split, and the organs themselves cease to fully cope with their function.

All symptoms of Alport's syndrome are divided into two groups - renal and extrarenal manifestations. Among the kidneys, two main signs are diagnosed: hematuria (traces of blood in the urine) and proteinuria (proteins in the urine). Often they are combined under the name "isolated urinary syndrome".

Isolated urinary syndrome in children can be noticed not immediately. Visible signals appear only at the 3-5th year of life, sometimes even at 7-10 years. But the smallest droplets of blood in the urine are always present, even if at first they are not visible - this is asymptomatic microhematuria. Therefore, hematuria is considered the main specific symptom of Alport syndrome.

In about half of the cases, the trigger for the appearance of blood in children's urine is an infection. Renal symptoms appear 1-2 days after SARS. Boys also develop proteinuria, but later, usually after 10 years of age. In girls, this symptom is either smoothed out or not at all.

Extrarenal symptoms of congenital nephritis appear later. This is:

• hearing loss (first the child ceases to distinguish between high sounds, then ordinary speech);
• various eye disorders;
• lag in physical development;
• congenital anomalies (deformed ears, high palate, fused or additional fingers - no more than 7 signs);
• rarely - leiomyomatosis (growth of smooth muscle fibers) of the esophagus, trachea, bronchi.

As the disease progresses, the classic signs of kidney failure appear: yellowish and dry skin, dry mouth, decreased urine output, etc. Increased pressure in the renal vessels - hypertension.

Classification

There are two classifications of Alport syndrome in children. The first is genetic, according to the type of inheritance of the anomaly.

In accordance with this classification, three types of congenital nephritis are distinguished:

• X-linked dominant, or classic (about 80% of all patients with SA);
• autosomal recessive (15% of children with a congenital anomaly);
• autosomal dominant (the rarest type, about 5% of patients).

The second, main classification names three variants of kidney disease:

1. Nephritis accompanied by hematuria, hearing loss and vision problems (eye lesions). This is an X-dominant type of birth defect.
2. Nephritis with hematuria, but without involvement of the sense organs. Corresponds to the autosomal recessive form.
3. Benign familial hematuria.

The first two options are progressive renal disease, the inevitable outcome of which is chronic renal failure. With benign familial hematuria, CRF does not develop, and the quality and life expectancy do not suffer in any way.

Diagnostics

These signs include:

1. In the family there are cases of hematuria, in the family there were cases of death from chronic renal failure.
2. In the family, the child is diagnosed with hematuria and/or proteinuria.
3. Specific changes in the patient's basement membrane of the renal glomeruli (according to the results of a biopsy).
4. Congenital pathology of vision.
5. Hearing loss (detected by audiometry).

If Alport syndrome is suspected, a number of traditional diagnostic methods are used:

• collection of anamnesis (information about the presence of the same symptoms and deaths from CRF in blood relatives);
• physical methods (palpation, tapping);
• laboratory tests (clinical urinalysis, etc.);
• Ultrasound and kidney biopsy.

Experts also recommend a DNA test for family members of a young patient using DNA probes. This allows you to determine the carrier of the mutant gene. In addition, there is the possibility of using DNA probes for prenatal diagnosis of Alport's syndrome, even during the mother's pregnancy. This is especially important if the family is expecting a boy - SA is more severe in men.

Without fail, differential diagnosis is also required: to delimit congenital nephritis from nephropathy and acquired glomerulonephritis.

Treatment

At the initial stage of congenital nephritis, powerful complex therapy is not required.

When making a renal diagnosis, the following therapeutic measures for children are necessary:

• lack of serious physical exertion (exemption from physical education lessons);
• constant walks;
• balanced diet;
• herbal medicine for the appearance of blood in children's urine (nettle and yarrow infusion, chokeberry juice);
• vitamins A and E, B6 (pyridoxine) to improve metabolism (courses of 2 weeks);
• for the same purposes - injections of cocarboxylase.

When chronic renal failure passes into the most dangerous, terminal stage, permanent hemodialysis is required. In the most severe cases, a kidney transplant.

Forecast

The prognosis for Alport syndrome depends on two factors: the variant of the disease and the sex of the child. The classical, X-dominant form of Alport's syndrome progresses most rapidly in boys.

In this case, chronic renal failure is diagnosed in all patients under 60 years of age, and in 50% - up to 25 years. If there are men in the family with the same variant of nephritis, then the time of onset of end-stage renal failure can be easily predicted, it will be the same. Women have no such dependence.

In the autosomal recessive type, kidney failure develops a little more slowly, but there is a risk that CRF will go into the terminal stage by the age of 30.

With an autosomal dominant form, the course and prognosis are the most favorable: the situation does not reach chronic renal failure. This form corresponds to benign familial hematuria. Specific therapy in this case is not carried out, the presence of blood in the urine does not threaten human life. All that is needed is constant medical monitoring of the patient's condition.

For the first time, this syndrome was described by the English physician Arthur Alport in 1927, who observed a whole family with total renal failure and simultaneous damage to the organs of vision and hearing in several generations.

Subsequently, conclusions were drawn about the genetic origin disease, which was ultimately proven in practice.

What it is?

Alport syndrome is a rare genetic disease associated with a violation of the structure of the fibrillar collagen protein, which is part of the kidneys, organs of vision and hearing of a person.

Due to the pathology, the patient develops renal failure, hearing deteriorates and visual acuity decreases. The disease is characterized by constant progress.

In medical practice, this syndrome has other names - hereditary nephritis or familial glomerulonephritis. The disease is hereditary and is associated with a pathology in one of the genes that is responsible for the structure of the collagen protein.

This compound serves as an integral part of the cochlear apparatus of the hearing organs, the lenses of the eyes and the glomerular apparatus of the kidneys. Due to this, the patient simultaneously develops a number of symptoms in the relevant organs: kidney failure, visual impairment and hearing loss.

According to the international classification according to ICD-10 has the code Q87.8(“Other Congenital Anomaly Syndromes”). That is, the disease refers to congenital pathologies with chromosomal abnormalities.

According to statistics, the number of people with this anomaly in the genes is about 0.017% throughout the planet, in the countries of North America the figure is several times higher. It is noticed that the mutated gene is more often activated in males.

Disease classification

Allocate 3 basic shapes diseases:

1. Dominant type of inheritance connected to the X chromosome. Thinning and splitting of the basal membrane in the kidneys, consisting of collagen, develops. Symptoms: hearing impairment, decreased vision, nephritis and hematuria. Constantly evolving.
2. Autosomal recessive type of inheritance. The clinical picture is similar to the previous type, but without hearing loss.
3. Autosomal dominant type of inheritance. It is called benign familial hematuria. Renal failure does not develop, the course of the disease is favorable.

Causes

The main reason is the mutation of the genes responsible for the code of collagen chains.

This pathology is usually transmitted from parents to, in rare cases it occurs independently (20% of cases). Moreover, the mother passes on the X chromosome to the son and daughter, and the father can only pass on to the daughter.

Probability of developing the disease increases many times if close relatives had other chronic diseases of the genitourinary system. It is also noticed that the disease can be triggered by additional factors:

• infectious diseases (viral, bacterial and fungal);
• trauma;
• taking medications;
• vaccinations;
• increased mental and physical stress;
• stress and emotional overwork.

Symptoms of the disease

The first symptoms appear aged 3-6 years. Gene mutation leads to collagen deficiency, which in turn negatively affects the condition of the basement membrane in the kidneys, eye lenses and the structure of the inner ear. These organs are less functional.

First of all, the kidneys suffer - the ability to filter worsens, as a result of which proteins, toxins and red blood cells begin to enter the blood. Develops progressive renal failure.

Simultaneously and with a delay, there is a decrease in visual acuity and hearing impairment. Symptoms tend to constantly grow and progress. The child may have additional symptoms:

• blood in the urine;
• elevated levels in the blood and urine;
• anemia;
• symptoms of intoxication (nausea, vomiting, weakness);
• muscle pain;
• jumps in blood pressure;
• decreased physical activity;
• headache;
• insomnia;
• increase in body temperature;
• chills;
• lagging behind in development from peers;
• hearing loss (inability to distinguish between low and high tones);
• lens anomalies.

In the future, without adequate treatment, the disease can become chronic, which is characterized by:

• chronic fatigue;
• constant malaise;
• dry skin;
• loss of appetite;
• weight loss;
• unpleasant taste in the mouth;
• mental retardation and lethargy;
• constant thirst and dry mouth;
• pale skin color.

Diagnostic measures

First of all, the doctor studies the medical history of the parents, since the disease is transmitted from parents to children. in 4 cases out of 5. He pays attention to the following details in the child and parents:

• the presence of hematuria;
• kidney biopsy showed abnormalities in the basement membrane structure;
• congenital problems with vision and hearing;
• in the family there were cases of renal failure with a fatal outcome;
• there is a constant decrease in hearing and vision in the child.

Enough the presence of 3 signs to almost certainly make a diagnosis. Further studies will be assigned in the form of:

• kidney,
• biopsies of collagen structures,
• radiography,
• urine and blood
• consultations of a geneticist and a nephrologist.

How to treat pathology?

To date, the disease cannot be completely cured.

Complex of therapeutic measures helps to stop the progress of the disease. For this, medications and special nutrition are used, and there is no specific drug against this ailment.

Angiotensin-converting enzyme (ATP) inhibitors, as well as angiotensin blockers, are prescribed to slow down the development of renal failure. This reduces proteinuria (the level of protein in the urine) and normalizes kidney function.

Additional medications may include Erythropoietin in the presence of anemia and drugs to normalize blood pressure. Perhaps peritoneal dialysis and. In severe cases, the patient need a kidney transplant regardless of age.

As adjuvant therapy For children, it is important to follow a number of rules:

1. reduce physical activity (up to exemption from physical education lessons);
2. take vitamins A, B6 and E to normalize metabolic processes in the body;
3. take walks in the fresh air;
4. engage in herbal medicine to improve the functionality of the kidneys and cleanse the blood (use decoctions and infusions of yarrow, nettle and chokeberry juice).

It is worth considering separately nutrition, which directly affects the kidneys and can both help and harm. The patient is forbidden to eat fatty, fried, salty, smoked and spicy. These types of foods overload the kidneys and can cause the disease to progress.

Also, you can not drink alcohol, with the exception of red wine in small quantities and only at the discretion of a doctor. Dangerous for health are any products with dyes in the composition (colored soda, jelly products with dye, etc.).

All food should be nutritious and contain as many vitamins as possible. At the same time, food should be well absorbed and not overload the digestive system, which affects the functioning of the kidneys. Lean meats (veal, lean beef), fish, seafood, poultry, as well as various vegetables and fruits are suitable for this.

Forecast

The prognosis depends on the form of the disease and the gender of the person. In the male line, the syndrome develops according to a similar scenario, so the father's history data can help predict the course of the disease in his son, such a dependence is not observed.

most dangerous is the X-dominant form, progressing rather quickly and posing a threat to life due to chronic renal failure. However, it is difficult to make an accurate prediction.

In contrast to the X-dominant form, the autosomal dominant type is less aggressive, and renal failure is less pronounced. It is possible to slow down the development of symptoms almost completely. The prognosis is favorable in most cases. The patient only needs constant monitoring of the condition of the kidneys and compliance. Medical therapy is usually not used.

Alport syndrome cannot be avoided as it is a genetic disorder. There are no effective preventive measures. There are also no specific drugs against the disease. The main thing is to control the patient's condition.

When a disease is detected, it is necessary to undergo all examinations and follow the recommendations of doctors.

The only truly effective way kidney transplant, which is carried out with serious renal failure and a threat to the life of the patient.

Find out how a kidney transplant operation works from the video:

Alport's syndrome is a genetic disorder of the kidneys, accompanied by a decrease in visual acuity and hearing. According to statistics, about 17 cases are diagnosed per 100 thousand people. It is most common in men, but women also get sick. Usually the first symptoms appear at the age of 3-8 years, but it can also occur without characteristic signs.

In official medicine, there are several forms and stages of Alport Syndrome. Each of them has a number of characteristic symptoms, as well as the severity of the course of the disease. The main forms of the syndrome include:

1. Hereditary nephritis in children is characterized by the presence of only renal symptoms. At the same time, the decrease in hearing and vision in patients is not observed.
2. When examining kidney tissue, an isolated thinning of the basement membranes occurs.
3. The disease is accompanied not only by pathologies of the kidneys, but also manifests itself in the form of hearing and vision impairment.

Alport syndrome is classified according to the severity and rate of progression of symptoms. There are 3 types:

1. The disease progresses extremely quickly, and goes into renal failure. In this case, the symptoms are pronounced.
2. The disease progresses quite quickly, but does not affect hearing and vision.
3. The course of the disease is benign. There are no characteristic symptoms, as well as progression.

Reasons for development

The only cause of Alport syndrome in humans is a genetic mutation. 3 genes are damaged, which are located on the 2nd chromosome. It is in them that information is stored about the chains of collagens that affect the functioning of the kidneys.

The damaged gene is most often inherited by a child from his parents on the X chromosome. In this regard, the pathology can be transmitted to children of any sex from the mother, and from the father - only to the girl. The probability of being born with kidney damage is higher if there are people in the family with hereditary diseases of the urinary system.

For every fifth birth of a child with Alport syndrome, there is an accidental gene mutation. At the same time, parents and close relatives have no genetic disorders and perfectly healthy kidneys.

Symptoms

The clinical symptoms of Alport's syndrome are pronounced. The initial stage is accompanied by hearing loss and the presence of blood in the urine.

However, if the disease progresses, then the symptoms are more pronounced. Intoxication of the body occurs, and anemia develops. This is due to a sharp decrease in hemoglobin levels. As a result, additional symptoms appear:

• drops in blood pressure;
• frequent headache;
• rapid shallow breathing;
• noise in ears;
• fast fatiguability.

Another characteristic feature is a violation of the biological rhythm. Sleepiness during the day and insomnia at night most often occurs in young children and the elderly. General symptoms depend on the age and health status of the patient.

The chronic form of Alport's syndrome is accompanied by symptoms such as:

• frequent urination that does not bring relief;
• malaise;
• the presence of blood in the urine;
• convulsions;
• general weakness;
• nausea accompanying vomiting;
• lack of appetite;
• chest pain;
• bruising and itchy skin.

In rare cases, a patient with chronic Alport syndrome falls into unconsciousness or suffers from confusion. However, in children, such symptoms practically do not occur.

Treatment Methods

Alport syndrome is currently considered an incurable disease. But there are studies based on the results of which (with the progression of renal failure), it is effective to use ACE inhibitors - drugs used to treat and prevent heart disease. According to the second studies, it is effective to use ATII receptor antagonists. Both types of drugs reduce intraglomerular pressure, which can significantly reduce proteinuria. In addition, inhibition of angiotensin-II can reduce vascular sclerosis.

At the very beginning, there is a study whose task is to prove the effect of cyclosporine on the normalization of renal function. But this drug in some cases leads to an acceleration of interstitial fibrosis.

Modern laboratories are studying the treatment of the disease with the help of gene therapy, but it is premature to talk about any results.

Shock, complex treatment is applicable only if there is a clear threat to life. At the initial stage, the disease is not treated.

If kidney symptoms appear in a child, it is necessary to adhere to a special regimen and follow the doctor's recommendations, which consist of the following measures:

1. The child should be exempt from serious physical exertion - it is not recommended to attend physical education classes and go to sports sections.
2. Frequent outdoor walks are recommended.
3. When blood in the urine or other symptoms appear, herbal medicine can be used. It is effective to drink chokeberry juice, as well as a decoction or infusion of yarrow and nettle.
4. You should eat right. Smoked, salty, fatty, spicy and spicy dishes should be absent from the diet. It is best to avoid products that contain artificial colors. Alcohol with such a disease is completely prohibited, but with the development of anemia, the patient can drink a small amount of dry red wine.
5. To improve metabolism, you need to drink a complex of vitamins: E, A and B6. It is better to take courses for two weeks.
6. To increase metabolism, it is also recommended to inject Cocarboxylase.

Genetically determined non-immune glomerulopathy, occurring with hematuria, a progressive decrease in renal function, is Alport's syndrome or hereditary nephritis. It is manifested by a complex of pathologies: the presence of nephritis with hematuria, hearing loss and vision pathology. In this article, we will tell you about the main causes and symptoms of the syndrome, as well as how it is treated in a child.

Causes of Alport syndrome in children

According to epidemiological studies conducted in 13 regions of Russia, this disease occurs with a frequency of 17 per 100,000 children [Ignatova M. S, 1999].

Etiology of Alport syndrome

The genetic basis of the disease is a mutation in the a-5 gene of the type IV collagen chain. This type is universal for the basement membranes of the kidney, cochlear apparatus, lens capsule, retina and cornea of ​​the eye, which has been proven in studies using monoclonal antibodies against this collagen fraction. Recently, the possibility of using DNA probes for prenatal diagnosis of the disease has been pointed out [Tsalikova F.D. et al., 1995].

The importance of testing all family members using DNA probes to identify carriers of the mutant gene is emphasized, which is of great importance when conducting medical genetic counseling for families with this disease. However, up to 20% of families do not have relatives suffering from kidney disease, which suggests a high frequency of spontaneous mutations of the abnormal gene.

Most patients with Alport's syndrome, families have people with kidney disease, hearing loss and vision pathology, family marriages between people with one or more ancestors matter, because. in the marriage of related individuals, the probability of obtaining the same genes from both parents increases [Fokeeva V. V. et al., 1988]. Autosomal dominant and autosomal recessive and dominant, X-linked transmission pathways have been established.

In babies, three variants of Alport syndrome are more often distinguished:

• the syndrome itself
• hereditary nephritis without hearing loss,
• familial benign hematuria.

The pathogenesis of Alport's syndrome

It is based on a combined defect in the collagen structure of the basal membrane of the glomeruli of the kidneys, structures of the ear and eye. The gene for the classic syndrome is located at the locus 21-22 q of the long arm of the X chromosome. In most cases, it is inherited in a dominant type linked to the X chromosome. In this regard, in men, Alport syndrome is more severe, since in women the function of the mutant gene is compensated by a healthy allele of the second, intact chromosome.

When examining a kidney biopsy according to electron microscopy, the following symptoms are observed: ultrastructural changes in the glomerular basement membrane: thinning, disruption of the structure and splitting of the glomerular basement membranes with a change in its thickness and uneven contours. In the early stages of the disease, the defect determines the thinning and fragility of the glomerular basement membranes.

Thinning of the glomerular membranes is more benign and is more common in girls. A more constant electron microscopic sign in this disease is the splitting of the basement membrane, and the severity of its destruction correlates with the severity of the process.

What are the symptoms of Alport syndrome in children?

The first symptoms of the disease in the form of an isolated urinary syndrome are more often detected in children of the first three years of life. In most cases, the disease is discovered incidentally. Urinary syndrome is detected during a preventive examination of a child, before admission to a children's institution or during SARS. In the case of the appearance of pathology in the urine during ARVI, in the syndrome, in contrast to acquired glomerulonephritis, there is no latent period.

How does Alport syndrome manifest itself in the initial stage?

In the initial stage, the child's well-being suffers little, the symptoms are not clearly expressed, treatment is carried out according to the doctor's recommendations. A characteristic feature is the persistence and persistence of the urinary syndrome. One of the main signs is hematuria of varying severity, observed in 100% of cases. An increase in the degree of hematuria is noted during or after respiratory tract infections, exercise, or after preventive vaccinations. Proteinuria in most cases does not exceed 1 g / day, at the beginning of the disease it can be intermittent, as the process progresses, proteinuria increases. Periodically, leukocyturia with a predominance of lymphocytes may be present in the urinary sediment, which is associated with the development of interstitial changes.

In the future, there is a violation of the partial functions of the kidneys, a deterioration in the general condition of the patient: intoxication, muscle weakness, arterial hypotension, often hearing loss (especially in boys), sometimes visual impairment. Intoxication is manifested by pallor, fatigue, headaches.

Hearing loss is a symptom of Alport's syndrome.

In the initial stage of the disease, hearing loss in most cases is detected only with the help of audiography. Hearing loss can occur at various times during childhood, but hearing loss is most often diagnosed between the ages of 6 and 10 years. It begins with high frequencies, reaching a significant degree with air and bone conduction, moving from sound-conducting to sound-perceiving hearing loss. Hearing loss may be one of the first symptoms of the disease and may precede urinary syndrome.

Decreased vision - a symptom of Alport's syndrome

In 20% of cases, patients have changes in the organs of vision. Anomalies from the side of the lens are most often detected: spherofokia, anterior, posterior or mixed lenticonus, various cataracts. In families with this disease, there is a significant incidence of myopia. A number of researchers constantly note bilateral perimacular changes in these families in the form of bright whitish or yellowish granulations in the area of ​​the corpus luteum. They consider this symptom to be a permanent symptom that has a high diagnostic value in this disease. K. S. Chugh et al. (1993) in an ophthalmological examination revealed a decrease in visual acuity in patients in 66.7% of cases, anterior lenticonus in 37.8%, retinal spots in 22.2%, cataracts in 20%, keratoconus in 6.7 %.

Features of Alport syndrome in children

In some children, especially in the formation of renal failure, a significant lag in physical development is noted. As renal failure progresses, arterial hypertension develops. In a child, its symptoms are more often detected in adolescence and in older age groups. When diagnosed, treatment is carried out immediately.

It is characteristic that patients with Alport syndrome have a variety of (more than 5 - 7) stigmas of connective tissue dysembryogenesis [Fokeeva VV, 1989]. Among the connective tissue stigmas in patients, the most common hypertelorism of the eyes, high palate, malocclusion, abnormal shape of the auricles, curvature of the little finger on the hands, "sandal gap" on the feet. The disease is characterized by the following symptoms: uniformity of dysembryogenesis stigmas within the family, as well as a high frequency of their spread among relatives of the probands through which the disease is transmitted.

In the early stages of the disease, an isolated decrease in the partial functions of the kidneys is detected: the transport of amino acids, electrolytes, concentration function, acidogenesis, in the future, changes relate to the functional state of both the proximal and distal nephron and are in the nature of combined partial disorders. The decrease in glomerular filtration occurs later, more often in adolescence. As it progresses, anemia develops.

Thus, the staging of the course of the disease is characteristic: first, a latent stage or latent clinical symptoms, manifested by minimal changes in the urinary syndrome, then a gradual decompensation of the process occurs with a decrease in renal functions with overt clinical symptoms (intoxication, asthenia, developmental delay, anemization). Clinical symptoms usually appear regardless of the layering of the inflammatory reaction.

The syndrome can manifest itself at different age periods, which depends on the action of the gene, which is in a repressed state until a certain time.

How is Alport syndrome diagnosed in children?

The following criteria are proposed:

• The presence in each family of at least two patients with nephropathy,
• Hematuria as a leading symptom of nephropathy in the proband,
• The presence of hearing loss in at least one of the family members,
• Development of CRF in one relative or more.

When diagnosing a variety of hereditary and congenital diseases, a large place belongs to an integrated approach to examination and, above all, paying attention to the data obtained when compiling a child's pedigree. The diagnosis of Alport's syndrome is considered eligible in cases where 3 out of 4 typical signs are found in a patient: the presence of hematuria and chronic renal failure in the family, the presence of neurosensory hearing loss in the patient, pathology of vision, the detection of signs of splitting of the glomerular basement membrane with a change in its thickness and uneven contours in the electron microscopic characteristic of the biopsy specimen with a change in its thickness and uneven contours [Ignatova M. S, 1996].

Clinical and genetic methods for the study of Alport's syndrome

Before treatment begins, the patient is examined, which should include clinical and genetic methods of research, a directed study of the history of the disease, a general examination of the patient, taking into account diagnostically significant criteria.

1. In the stage of compensation, pathology can be caught only by focusing on such syndromes as the presence of hereditary burden, hypotension, multiple stigmas of dysembryogenesis, and changes in the urinary syndrome.
2. In the stage of decompensation, estrarenal symptoms may appear, such as severe intoxication, asthenization, lag in physical development, anemization, which manifest and intensify with a gradual decrease in renal functions. In most patients, with a decrease in renal functions, there is a decrease in the function of acido- and aminogenesis, in 50% of patients a significant decrease in the secretory function of the kidneys, limiting the limits of fluctuations in the optical density of urine, a violation of the filtration rhythm, and then a decrease in glomerular filtration.
3. The stage of chronic renal failure is diagnosed in the presence of patients for 3-6 months. and more elevated levels of urea in the blood serum (more than 0.35 g / l), a decrease in glomerular filtration rate up to 25% of the norm.

Differential diagnosis of Alport syndrome

It has to be carried out with the hematuric form of acquired glomerulonephritis. Acquired glomerulonephritis often has an acute onset, a period of 2–3 weeks after infection, extrarenal signs, including hypertension from the first days (with Alport's syndrome, on the contrary, hypotension), a decrease in glomerular filtration at the onset of the disease, no violation of partial tubular functions, then as in hereditary they are present. Acquired glomerulonephritis occurs with more pronounced hematuria and proteinuria, with increased ESR. Typical changes in the glomerular basement membrane characteristic of the syndrome are of diagnostic value. Treatment must be started promptly.

Differential diagnosis from dysmetabolic nephropathy is carried out with chronic renal failure, heterogeneous kidney diseases are clinically detected in the family, and there may be a spectrum of nephropathy from pyelonephritis to urolithiasis. Often there are complaints of pain in the abdomen and periodically during urination, in the urine sediment - oxalates.

If a disease is suspected, the patient must be referred to a specialized nephrology department to clarify the diagnosis.

How to treat Alport syndrome in children?

The treatment regimen provides for restriction from heavy physical exertion, stay in the fresh air. During the period when the treatment is carried out, a complete diet is indicated, with a sufficient content of complete proteins, fats and carbohydrates, taking into account kidney function. Of great importance is the identification and sanitation of chronic foci of infection. Of the drugs, ATP, cocarboxylase, pyridoxine (up to 50 mg / day), vitamin B5, carnitine chloride are used. Courses are held 2-3 times a year. With hematuria, herbal medicine is prescribed - nettle nettle, chokeberry juice, yarrow.

In foreign and domestic literature, there are reports of treatment with prednisolone and the use of cytostatics. However, it is difficult to judge the effect.

Alport Syndrome Treatment

In chronic renal failure, hemodialysis and kidney transplantation are used.

MS Ignatova (1999) believes that the main method in the development of chronic renal failure is the timely implementation of kidney transplantation, which is possible without prior extracorporeal dialysis. The problem of using genetic engineering methods is topical.

There is a need for continuity in the constant monitoring of patients and the transfer of children by a pediatrician directly to a nephrologist. Dispensary observation is carried out throughout the life of the patient.

Now you know the main symptoms and treatments for Alport syndrome in children. Health to your baby!

Alport syndrome (familial glomerulonephritis) is a rare genetic disorder characterized by glomerulonephritis, progressive renal failure, sensorineural hearing loss, and eye involvement.

The disease was first described by British physician Arthur Alport in 1927.

Alport syndrome is very rare, but in the US it is responsible for 3% of ESRD in children and 0.2% in adults, and is also considered the most common type of familial nephritis.

The type of inheritance of Alport syndrome can be different:

X-linked dominant (XLAS): 85%.
Autosomal recessive (ARAS): 15%.
Autosomal dominant (ADAS): 1%.

The most common X-linked form of Alport syndrome results in end-stage renal disease in men. Hematuria usually occurs in boys with Alport syndrome in the first years of life. Proteinuria is usually absent in childhood, but the condition often develops in men with XLAS and in both sexes with ARAS. Hearing loss and eye involvement are never detected at birth but occur in late childhood or adolescence, shortly before kidney failure develops.

Causes and mechanism of development of Alport syndrome

Basement membranes are thin film structures that support tissues and separate them from each other. In violation of the synthesis of type IV collagen, the glomerular basement membranes in the kidneys are not able to normally filter toxic products from the blood, passing proteins (proteinuria) and red blood cells (hematuria) into the urine. Abnormalities in type IV collagen synthesis lead to kidney failure and kidney failure, which is the main cause of death in Alport syndrome.

Clinic

Proteinuria is usually absent in childhood, but sometimes develops in boys with X-linked Alport syndrome. Proteinuria is usually progressive. Significant proteinuria in female patients is rare.

Hypertension is more commonly present in male patients with XLAS and in patients of both sexes with ARAS. The frequency and severity of hypertension increases with age and as renal failure progresses.

Sensorineural hearing loss (hearing impairment) is a characteristic manifestation of Alport syndrome, which is observed quite often, but not always. There are entire families with Alport syndrome who suffer from severe nephropathy but have normal hearing. Hearing impairment is never detected at birth. Bilateral high-frequency sensorineural hearing loss usually presents in the first years of life or early adolescence. At an early stage of the disease, hearing impairment is determined only by audiometry.

As it progresses, the hearing loss extends to low frequencies, including human speech. After the onset of hearing loss, kidney involvement should be expected. American scientists claim that with X-linked Alport syndrome, 50% of men suffer from sensorineural hearing loss by the age of 25, and by the age of 40 - about 90%.

Anterior lenticonus (protrusion of the central part of the lens of the eye forward) occurs in 25% of patients with XLAS. Lenticonus is not present at birth, but over the years it leads to a progressive deterioration of vision, which forces patients to change their glasses frequently. The condition is not accompanied by eye pain, redness, or impaired color vision.

Retinopathy is the most common manifestation of Alport's syndrome on the part of the organ of vision, affecting 85% of men with an X-linked form of the disease. The onset of retinopathy usually precedes kidney failure.

Posterior polymorphic corneal dystrophy is a rare condition in Alport syndrome. Most have no complaints. Mutation L1649R in the collagen gene COL4A5 can also cause retinal thinning, which is associated with X-linked Alport syndrome.

Diffuse leiomyomatosis of the esophagus and bronchial tree is another rare condition seen in some families with Alport syndrome. Symptoms appear in late childhood and include swallowing disorders (dysphagia), vomiting, epigastric and retrosternal pain, frequent bronchitis, shortness of breath, cough. Leiomyomatosis is confirmed by computed tomography or MRI.

Autosomal recessive form of Alport syndrome

Autosomal dominant form of Alport syndrome

Diagnosis of Alport's syndrome

British experts, based on new data (2011) on genetic mutations in patients with X-linked Alport syndrome, recommend testing for COL4A5 gene mutation if the patient meets at least two diagnostic criteria according to Gregory, and analysis of COL4A3 and COL4A4 if the COL4A5 mutation is not autosomal inheritance is found or suspected.

Alport Syndrome Treatment

Some researchers suggest that ciclosporin may reduce proteinuria and stabilize renal function in patients with Alport syndrome (studies have been small). But reports say that patients' response to ciclosporin is highly variable, and sometimes the drug can precipitate interstitial fibrosis.

In renal failure, standard therapy includes erythropoietin to treat chronic anemia, drugs to control osteodystrophy, correction of acidosis, and antihypertensive therapy to control blood pressure. Hemodialysis and peritoneal dialysis are used. Kidney transplantation is not contraindicated for patients with Alport's syndrome: transplantation experience in the USA has shown good results.

Gene therapy for various forms of Alport syndrome is a promising treatment option, which is currently being actively studied by Western medical laboratories.

Konstantin Mokanov