Characteristic manifestations of Louis Bar syndrome. Louis-Bar syndrome (ataxia-telangiectasia)

Synonyms of Louis-Bar syndrome. S. Boder-Sedgwick. Cephalo-oculocutaneous telangiectasia. Cerebelloculocutaneous telangiectasia. Telangiectatic ataxia. Cerebellar atrophy with oculocutaneous telangiectasias and bronchiectasis. Telangiectasia and ataxia syndrome.

Definition of Louis-Bar syndrome. Rare phakomatosis in children. Refers to neurocutaneous syndromes.

Symptomatology of Louis-Bar syndrome:
1. Cerebellar ataxia, abasia and astasia, which first appear in early childhood and slowly progress; By the time of puberty, free gait and standing are usually impossible. At the same time, speech disorders develop (monotonous scanned speech or regular dysarthria), which are also progressive in nature.
2. Absence of pyramidal signs, reflexes are normal or weakened. Muscle tone (after the initial rigidity-like increase) is usually reduced. Normal sensitivity. No paresis.
3. Slowly developing symmetrical telangiectasias of the skin and mucous membranes, especially the skin of the face and conjunctiva (an early symptom that can manifest as rapidly passing conjunctivitis!). Frequent development of café-au-lait plaques, facial skin atrophy, premature graying of hair (at school age).
4. Recurrent pulmonary infections, sometimes with development.
5. Hypersalivation.
6. Small stature and general dystrophy.
7. At the onset of the disease, intellectual development is normal; later, mental development is delayed.
8. Pneumoencephalographic data: signs of cerebellar atrophy.
9. Ataxia - telangiectasia is very often combined with thymic hypoplasia, specific dysgammaglobulinemia (gamma Au, globulin deficiency) and a tendency to malignant processes in the reticuloendothelial system (lymphosarcoma, reticulosis, etc.).
10. The prognosis is poor. Most of the patients observed so far died during puberty.

Etiology and pathogenesis of Louis-Bar syndrome. A recessive hereditary disorder with genetically determined inhibition of cerebral vascularization. In one case, a translocation was established between two acrocentric chromosomes of group 13-14-15 (Bijl, Jansen, Ossentjuk, 1963). The significance of the excess urinary excretion of polypeptides found in some cases is still unclear.

Pathological anatomy. Primary chronic progressive cerebellar degeneration with pathological changes in Purkin cells and wrinkling of the white matter, as well as changes in veins (dilation, congestion, thinning of the walls), especially in the area of the pia mater of the cerebellum, as well as the cerebral hemispheres.

Differential diagnosis. In the initial stages: cerebellar form of cerebral palsy syndrome. S. Friedreich I (see). Cerebellar tumors. S. Sturge-Weber (see). S.v. Hippel-Lindau (see). S. Werner (see). S. Osier I (see).

Description:

Ataxia-telangiectasia (Louis-Bar syndrome) is a hereditary disease with cerebellar ataxia, telangiectasia, impaired immunity and a tendency to malignant neoplasms; increased fragility of chromosomes; patients' cells are sensitive to the effects of ionizing radiation. Frequency. 1:300,000 newborns.

Symptoms:

Damage to the central nervous system:
- Cerebellar appears from the first years of life (after the patient begins to walk) and progresses with age;
- Extrapyramidal symptoms - hypokinesia, choreoathetosis (may appear at an older age);
- Spinal-cerebellar ataxia with impaired deep and vibration sensitivity appears at the age of 12–15 years;
- Oculomotor (impaired functions of the oculomotor nerves).

Immunity disorders:
- Hypoplasia of the thymus;
-Decreased serum levels of IgG2 or IgA. IgE and IgM concentrations may be normal. Lymphopenia and decreased cellular immunity develop early in tests for intradermal administration of Ag.

Vascular damage. Telangiectasias are formations of venous origin that appear later than ataxia (at the age of 3–6 years), first on the conjunctiva (vascular “spiders”), then on the skin of the face, ears, elbows, popliteal fossae, and in places of skin friction.

Defeat of other systems:
-Early graying of hair
- Atrophic changes in facial skin
- Dark spots
-
- Slight growth retardation
- Mental retardation
- Frequent, sinusitis
- Neoplasms of various localizations (leukemia, medullosarcoma)
- Women are characterized by hypogenitalism; less pronounced in men
- Decreased glucose tolerance.

Causes:

The disease is associated with genetic disorders; a defective enzyme in ataxia-telangiectasia is DNA topoisomerase.

Treatment:

There is no effective treatment: symptomatic therapy, vitamin therapy and physiotherapy.

With this rare form of phakomatosis, neurological symptoms, skin manifestations in the form of spider-like proliferation of blood vessels (telangiectasia), and a decrease in the immunological reactivity of the body are observed. The disease is caused genetically and is inherited in an autosomal recessive manner.

A pathological examination reveals a decrease in the number of nerve cells and proliferation of blood vessels in the cerebellum.

The first signs of the disease appear between the ages of 1 and 4 years. The gait becomes unstable, awkward movements appear, and the fluency of speech (chanted speech) is disrupted. The progression of cerebellar disorders gradually leads to the fact that patients stop walking independently. Involuntary movements of the limbs and poor facial expressions are often observed. Speech is monotonous and poorly modulated.

Another characteristic sign of the disease is vascular changes in the form of telangiectasia, located on the mucous membrane of the eyes, mouth, soft and hard palate, and skin of the extremities. Telangiectasia usually occurs after ataxia, but can also be the first symptom of the disease.

Children with Louis-Bar syndrome often suffer from colds, inflammation of the paranasal sinuses, and pneumonia. These diseases often recur and take a chronic course. They are caused by a decrease in the protective immunological properties of blood and the absence of specific antibodies.

As the disease progresses, intellectual impairment intensifies, attention and memory become impaired, and the ability to abstraction decreases. Children become exhausted quickly. Changes in mood are noted. Tearfulness and irritability are replaced by euphoria and foolishness. Sometimes patients are aggressive. They lack a critical attitude towards their own defect.

In the treatment of Louis-Bar syndrome, general restoratives and drugs that improve the functionality of the nervous system are used. Attempts are being made to replace the missing immunological blood fractions by transplanting a thymus gland taken from a deceased newborn and introducing thymosin extract from the thymus gland.

Therapeutic and pedagogical measures are very limited due to frequent colds and the steady progression of the process, leading to severe intellectual impairment.

Symptoms

As a rule, symptoms of Louis Bar syndrome begin to appear at the age of five months to three years, but deviations are especially noticeable when the baby begins to move independently, albeit not over long distances.

Thus, signs of ataxia on the face: a shaky and uncertain gait, impaired coordination of movements, tremors of the limbs, swaying of the body and frequent twitching of the head. The characteristic signs in the affected body are often so obvious that the patient is simply unable to move independently. In addition, there is impaired speech, lack of tendon reflexes, muscle hypotonia, strabismus and other abnormalities in the structure and functionality of the eyes.

With this disease, infectious diseases of the respiratory tract and ear of a recurrent nature very often progress. This can be chronic rhinitis, otitis media, pharyngitis, sinusitis, bronchitis, and less commonly, pneumonia and pneumonia. However, it is important to understand that each subsequent relapse only worsens the general condition, hastening death.

Another eloquent symptom of Louis Bar syndrome is spider veins, which usually appear between 3 and 6 years of age. They are caused by pathogenic expansion of small capillaries, but may also indicate the presence of other diseases.

Telangiectasia begins on the eyeball in the form of trivial conjunctivitis, but very soon a characteristic visual defect predominates on the skin of the eyelids, neck, nose, face, elbows and back of the hand. Increased dryness of the skin, hyperemia, early hair loss and an increase in the number of vascular networks on the skin also predominate.

Louis Bar syndrome may be accompanied by the appearance of malignant neoplasms, represented by lymphoma and leukemia. However, it is advisable to study the clinic of these pathological processes on an individual basis.

Diagnostics

If a local physician suspects the presence of Louis Bar syndrome, he will refer him to a specialist. However, consulting with an immunologist is not at all enough, because you should also see a neurologist, dermatologist, ophthalmologist, pulmonologist, oncologist and otolaryngologist with your problem. It is extremely important to differentiate Louis-Bar syndrome from Rendu-Osler disease, Friedreich's attack, Pierre-Marie ataxia and, of course, the little studied Hippel-Lindau syndrome.

A neurologist will make the final diagnosis, but without detailed diagnostics it is impossible to do this. That is why it is imperative to undergo instrumental and laboratory tests to obtain a detailed clinical picture.

The most popular examination methods are presented below:

in a general blood test, a pathological decrease in the number of lymphocytes can be observed;
determining the level of blood immunoglobulins allows you to detect a decrease in IgA and IgE, as well as reliably determine the presence of autoantibodies to mitochondria, immunoglobulin and thyroglobulin;
Ultrasound helps characterize aplasia and hypoplasia of the thymus;
MRI of the brain to diagnose cerebellar degradation and pathogenic expansion of the fourth ventricle;
Radiography determines the presence of pneumonia, foci of pneumosclerosis, as well as the predominance of bronchiectasis changes.

When the neurologist has all the diagnostic results, as well as the preliminary conclusion of narrow specialists, he will finally decide on the final diagnosis and prescribe a specific treatment regimen.

Prevention

Preventive measures are not particularly effective, since the pathological process predominates during the direct formation of the embryo in the prenatal period.

The disease is inherited and predominates at the genetic level, so protecting your unborn child from a terrible fate is very problematic.

Doctors, when identifying a characteristic problem during one of the screenings during pregnancy, suggest that the expectant mother induce labor prematurely.

Treatment

Modern medicine has not yet discovered a panacea for this disease, and what can I say, doctors cannot even decide on a general treatment regimen. However, this clinical picture clearly requires an integrated approach.

A long course of antibacterial therapy is required, which allows you to quickly destroy secondary bacterial infections, as the main cause of immunodeficiency.
Along with taking antibiotics, a course of gamma globulins, immunostimulants, multivitamin complexes and even dietary supplements is also required for the overall strengthening of weakened human resources.
In childhood, physical therapy is required, which includes individual sessions with a speech therapist on speech production.

However, one way or another, therapy should be based on the underlying disease. If it is diabetes mellitus, then the treatment regimen cannot do without oral glucose-lowering drugs and insulin. If there is a rapidly progressing tumor, then immediate surgical removal is required. So when treating, it is important to take into account all the nuances, and then it will be truly effective.

Louis-Bar syndrome (congenital ataxia-telangi-ectasia - A-T) is a congenital immunodeficiency condition with a predominant lesion of the T-link of immunity, characterized by abnormal development of embryonic anlages and, apparently, incorrect interaction of ectoderm and mesoderm. Louis-Bar syndrome is a genetic disorder that is inherited in an autosomal recessive manner. First described in 1941 D. Louis-Barr. Population frequency is unknown. Sex ratio: m:f - 1:1.

Immunodeficiency and chromosomal instability are markers of A-T (Ataxia - Teteangiectasia Mutated), which encodes the synthesis of the kinase of the same name. Cells of patients with A-T are characterized by increased sensitivity to radiation, defects in the cell cycle, but clinical manifestations and immunological disorders have significant differences, there is an increased incidence of malignant tumors and spontaneous chromosomal instability, chromosomal breakdowns involving mainly the 7th and 14th chromosomes .

It is known that the cell cycle is divided into 4 phases: mitosis (M) and DNA synthesis (S), separated by two breaks Gl and G 2. The sequence of the cell cycle is as follows: G 1 - S - G 2 - M. After exposure to ionizing radiation, DNA double-strand breaks occur. If DNA repair occurs, the cell cycle is restored; if not, cell death occurs by apoptosis or a mutant clone develops. Normally, the cell cycle when exposed to radiation can be blocked at two critical points - the transition from the Gl phase to the S phase and/or from the G 2 phase to the M phase. In A-T, control of the cell cycle is disrupted at critical points. Double-strand DNA breaks occur during recombination of immunoglobulin and T-cell receptor genes. Processes resembling the recombination of immunoglobulin genes occur during the maturation of brain neurons. It is obvious that it is with defects in DNA repair in these cases that many clinical and immunological manifestations in patients with A-T are associated, such as disturbances in the synthesis of immunoglobulins, the function of the genital organs and the nervous system.

Clinical manifestations of A-T may vary significantly in different patients. Progressive cerebellar ataxia and telengiectasia are present in everyone, and café au lait spots on the skin are common. The tendency to infections ranges from very severe to very moderate. The incidence of malignant neoplasms, mainly of the lymphoid system, is very high. Immunological changes in patients with A-T are disorders of cellular immunity in the form of a decrease in the number of T lymphocytes, inversion of the CD4+/CD8+ ratio (mainly due to a decrease in CD4+ cells) and a decrease in the functional activity of T cells. In terms of serum immunoglobulin concentrations, the most characteristic change is a decrease or absence of IgA; less often, immunoglobulin concentrations close to normal are detected, or disimmunoglobulinemia in the form of a sharp decrease in IgA, IgG, IgE and a significant increase in IgM. A characteristic disorder is the formation of antibodies in response to polysaccharide and protein antigens. Treatment methods for A-T have not been developed to date. Patients need palliative therapy for neurological and somatic disorders. In case of detection of serious immunological changes and/or chronic or recurrent bacterial infections, antibacterial therapy is indicated (duration is determined by the severity of immunodeficiency and infection), replacement therapy with intravenous immunoglobulin, and, if indicated, antifungal and antiviral therapy.

Clinical characteristics. The disease begins in early childhood and manifests itself primarily as cerebellar ataxia (100%). Rocking of the head and body, gait disturbance, intention tremor and choreoathetosis are noted (90-100%). Characteristic changes in the eyes are impaired movement of the eyeball (80-90%), nystagmus (90-100%) and strabismus. At the age of 2 to 6 years, telangiectasias appear on the conjunctiva and open areas of the body, the mucous membrane of the soft and hard palate. An important sign of the syndrome is chronic respiratory infections (sinusitis and pneumonia, 60-80%). Growth retardation, age spots or areas of depigmentation on the skin, scleroderma, muscle hypotonia, hyporeflexia and dysarthria are observed. Patients often develop malignant neoplasms, and in 10-30% the lymphoreticular system is affected.

A pathological examination reveals aplasia or hypoplasia of the thymus, a decrease in the size of the lymph nodes and spleen, signs of cerebellar degeneration, and fibrous ovarian dysplasia. With A-T, there is a violation of the B- and T-cell immune systems, which is expressed in the absence of serum immunoglobulins, mainly IgA, but sometimes IgG and IgE. Cytogenetic studies of lymphocytes often reveal various chromosomal aberrations and chromosome fragility. Patients die from pulmonary infections or from malignant neoplasms.

Neurological symptoms come first in the clinical picture, so the disease was initially described as cerebellar ataxia. Between the ages of 2 and 8 years, telangiectasias occur, which are usually located on the bulbar conjunctiva, between the angle of the eye and the limbus, and look like red convoluted vessels. Aplasia of the thymus gland, hypoplasia (underdevelopment) of the lymph nodes, spleen, group lymphatic follicles of the small intestine, and tonsils are observed. Children with Louis-Bar syndrome constantly experience hypoplasia (underdevelopment) or aplasia (complete absence) of the palatine tonsils. The lacunae of the tonsils are underdeveloped. Cervical lymph nodes are small and do not enlarge during infections. Almost all children with Louis-Bar syndrome develop chronic purulent sinusitis and often develop otitis media.

The diagnosis is made based on the clinical picture, as well as laboratory data. All patients with Louis-Bar syndrome almost completely lack T-suppressors. In some patients, cells cannot synthesize IgA, which is due to the absence of T helper cells. A- and b-proteins are found in the blood. The pathogenetic method of treatment is allotransplantation of the neonatal thymus gland. A course of injections of active factors of the thymus gland (T-activin, thymalin, thymacin, etc.) is prescribed, native plasma and normal human immunoglobulin are systematically administered.

Under our supervision was a girl K., she was admitted to the clinic at the age of 13 years and 10 months due to a congenital immunodeficiency condition with ataxia (Louis-Bar syndrome), chronic pneumonia, polysegmental pneumosclerosis, purulent deforming endobronchitis, bronchiectasis in the acute phase, right-sided large-focal pneumonia, complicated by generalized amyloidosis of internal organs: liver with the development of cirrhosis and liver failure, kidneys, spleen, intestines, anemia, cachexia.

When a mother complains of icteric discoloration of the skin, repeated vomiting, anorexia, general weakness, and emaciation. From the anamnesis it is known that she was born full-term, with a low weight of 2,700 g, with an Apgar score of 6-7 points. She was breastfed and did not get sick until she was a year old. From the second year of life, frequent colds were noted, emaciation began to progress, and she suffered from repeated pneumonia. Cerebellar ataxia was diagnosed at the age of 4 years. The girl was consulted at our clinic, and Louis-Bar syndrome was diagnosed in the Moscow clinic. Since then, the symptoms of degeneration and ataxia have progressed, and she has suffered repeated pneumonia. Chronic bronchiectasis was diagnosed. She was treated in hospital several times. For the last 2 years of her life, the girl has not walked; changes in the liver and kidneys associated with amyloidosis have occurred. 3 months before the last hospitalization, she was in the clinic, the diagnosis was confirmed, she received complex therapy - broad-spectrum antibiotics, detoxification therapy, immunotherapy. The girl's condition has stabilized. She was discharged home on a maintenance dose of medications that improve the metabolic processes of the liver and kidneys. 2 weeks before admission, the patient’s condition sharply worsened, jaundice increased, complete anorexia was observed, and repeated vomiting appeared. Sent to the clinic.

Upon admission, the general condition was serious. The girl is severely dystrophic. The skin and sclera are icteric, multiple “star-shaped” rash. The eyeballs have a pronounced vascular pattern. She is inhibited and answers questions sluggishly. The position in bed is horizontal, sitting with support. Visible mucous membranes are pale. The tongue is pink. Peripheral lymph nodes are small, single, up to 0.5-1.0 cm in diameter, submandibular lymph nodes are palpable. Pulse - 100. RR - 40. Blood pressure - 100/60 mm Hg. Above the lungs there is a pulmonary sound percussion, shortened in the lower parts, auscultation of breathing is hard, weakened in the lower parts, single moist fine bubbling rales are heard. The borders of the heart are expanded in diameter, the left one along the anterior axillary line. The tones are muted and rhythmic. The abdomen is enlarged in volume, soft on palpation, and there is no ascites. The liver is dense, palpated 4 cm below the costal arch, the spleen is dense, palpated 5 cm below the costal arch at the entrance to the pelvis. Urinates freely. The chair is decorated and straightens on its own.

Laboratory examinations

Blood test: Er. - 2.9 T/l, Hb - 90 g/l, C.P - 0.9, Lake. - 8.2 G/l, anisocytosis and poikilocytosis are pronounced, p/i - 14%, s/i - 20%, l. - 64%, m. - 2%, ESR - 6 mm/hour. Residual blood nitrogen - 54.5 g/l. Blood cholesterol - 4 µmol/l. AST - 0.35, ALT - 0.42. Total blood bilirubin - 84.8 mmol/l, direct - 74.2, indirect - 10.6.

Sublimate test - 1.6. Total blood protein - 64 g/l, albumin - 46.7, gamma globulins - 19%. Blood prothrombin - 75%.

Urinalysis: protein - 0.86 g/l, Lake. — 10-15, up to 25 in field view, Er. — 10 in the field of view, hyaline cylinders — 1-2, granular — 1-2 in the field of view.

On a chest x-ray: the lung tissue is moderately distended, especially in the lower lobes. The pulmonary pattern is strengthened, expanded, on the right in the middle lobe there is large-focal infiltration of the lung tissue without clear contours. The sinuses are free. The heart is normal. ECG: diffuse myocardial damage. Based on the anamnesis, objective data, clinical examination and observation, the above diagnosis was made.

Received therapy: intravenous drip of Ringer's solution, hemodez, plasma, corglucon, lasix, ampicillin intramuscularly, daily gamma globulin, sirepar, lipoic acid, methionine, prednisolone, oxygen therapy, diet No. 7.

Despite the therapy, the girl’s condition progressively worsened, the symptoms of liver and kidney failure increased, and daily diuresis decreased, in recent days up to 300 g per day. The number of wheezes in the lungs increased, and respiratory and heart failure increased. 18 days after admission to the hospital, the condition was agonizing, nosebleeds appeared, there was an admixture of blood in the stool, tar-like stools, and a liver smell appeared. The resuscitation measures carried out had no effect. Due to hepatic failure accompanied by respiratory and heart failure, the girl died on the 20th day of her stay in the clinic.

Pathological diagnosis

Basic: congenital immunodeficiency condition with ataxia - Louis-Bar syndrome. Chronic pneumonia. Polysegmental pneumosclerosis, purulent deforming endobronchitis, bronchiectasis in the acute stage, right-sided macrofocal pneumonia.

Complications: generalized amyloidosis of internal organs: liver with the development of cirrhosis and liver failure, kidneys, spleen, intestines. Anemia. Cachexia.

The peculiarity of this clinical case can be considered the rare frequency of occurrence, the characteristic clinical and laboratory picture of the disease, the slow progression of the development of Louis-Bar syndrome, and the age of the patient.