Ataxia telangiectasia is a hereditary disease manifested by cerebellar ataxia, telangiectasia of the skin and conjunctiva of the eyes, insufficiency of the T-cell link of immunity. The latter leads to the fact that disease is accompanied by frequent respiratory infections and a tendency to the appearance of malignant tumors. Pathology is diagnosed on the basis of anamnesis and clinical picture of the disease, immunogram data, results of ophthalmological and otolaryngological examination, MRI of the brain and lung x-ray. Currently, disease has no specific and effective treatment.
General information
Ataxia telangiectasia was first described in 1941 in France. There is no exact data on the frequency with which ataxia telangiectasia occurs among the modern population. According to some reports, this figure is 1 case per 40 thousand newborns. However, it should be borne in mind that when dying in early childhood, ataxia telangiectasia usually remains undiagnosed. It is known that the disease affects boys and girls equally often. In neurology, ataxia telangiectasia refers to the so—called phacomotoses – genetically determined combined lesions of the skin and nervous system. This group also includes Recklinghausen neurofibromatosis, Sturge—Weber angiomatosis, tuberous sclerosis, etc.
Causes and pathogenesis
The pathological changes accompanying ataxia telangiectasia are based on genetic disorders that lead to the development of congenital neuroectodermal dysplasia. ataxia telangiectasia is an autosomal recessive disease, i.e. it manifests itself clinically only when receiving a recessive gene from both parents at once.
Morphologically, ataxia-telangiectasia is characterized by degenerative changes in cerebellar tissues, in particular, the loss of granular cells and Purkinje cells. Degenerative changes can affect the dentate nucleus of the cerebellum (nucleus dentatus), the black substance (substantia nigra) and some parts of the cerebral cortex, sometimes the spinal cord pathways and the posterior pillars of the spinal cord are affected.
Ataxia telangiectasia is combined with hypoplasia or aplasia of the thymus, as well as with congenital deficiency of IgA and IgE. These disorders in the immune system lead to the appearance of frequent infectious diseases in patients, prone to a long and complicated course. In addition, immune disorders can potentiate the development of malignant neoplasms, often originating in the structures of the lymphoreticular system.
Symptoms
Ataxia. Most often, ataxia telangiectasia begins to manifest clinically at the age of 5 months to 3 years. In all cases of the disease, ataxia telangiectasia manifests itself with the appearance of cerebellar ataxia, the signs of which become apparent when the child begins to walk. There are disturbances of balance and gait, trembling during the motor act (intentional tremor), swinging of the trunk and head. Often, ataxia is so pronounced that a patient with ataxia telangiectasia cannot walk. Cerebellar ataxia is combined with cerebellar dysarthria, characterized by slurred chanted speech. There is muscle hypotension, a decrease or complete disappearance of tendon reflexes, nystagmus, oculomotor disorders and strabismus.
Telangiectasia. In most cases, the appearance of telangiectasias accompanying ataxia telangiectasia occurs at the age of 3 to 6 years. In some cases, their occurrence is noted at a later period and very rarely during the first month of life. Telangiectasia (vascular asterisks) are variously shaped reddish or pink spots or branching. They are caused by the expansion of small vessels of the skin. It should be noted that telangiectasia can be a manifestation of many other diseases (for example, rosacea, SLE, dermatomyositis, pigmented xeroderma, chronic radiation dermatitis, mastocytosis, etc.). However, in combination with ataxia, they give a clinical picture specific to ataxia telangiectasia.
Ataxia telangiectasia is characterized by the initial appearance of telangiectasias on the conjunctiva of the eyeball, where they look like “spiders”. Then vascular asterisks appear on the skin of the eyelids, nose, face and neck, elbow and knee bends, forearms, the back of the feet and hands. Telangiectasia can also be observed on the mucous membrane of the soft and hard palate. Vascular asterisks are most pronounced in those places of the skin where it is exposed to sunlight. First of all, this is a face where telangiectasias form whole “bundles”. At the same time, the skin loses its elasticity and becomes dense, which resembles the changes typical of scleroderma.
Cutaneous manifestations of ataxia-telangiectasia may include the appearance of freckles and coffee-colored spots with milk, areas of discolored skin. The presence of hypo- and hyperpigmentation makes the skin symptoms of ataxia telangiectasia similar to the clinic of poikiloderma. Many patients have dry skin and areas of hyperkeratosis. Hypertrichosis, early gray hair, skin elements resembling acne or manifestations of psoriasis may be observed.
Respiratory tract infections. The lesion of the immune system that characterizes ataxia telangiectasia leads to the occurrence of frequent recurrent infections of the respiratory tract and ear: chronic rhinitis, pharyngitis, bronchitis, pneumonia, otitis, sinusitis. Their features are: the blurring of the boundaries between the period of exacerbation and remission, the scarcity of physical data, poor sensitivity to antibacterial therapy and a long course. Each such infection can become deadly for a patient with ataxia-telangiectasia. Frequent lung diseases lead to the development of bronchiectasis and pneumosclerosis.
Malignant neoplasms. Among patients with ataxia telangiectasia, malignant tumor processes are noted 1000 times more often than the average population. The most common among them are leukemia and lymphoma. A feature of oncopathology in the case of ataxia telangiectasia is the increased sensitivity of patients to the effects of ionizing radiation, which completely excludes the use of radiation therapy in their treatment.
Diagnostics
The diagnosis of ataxia-telangiectasia requires a comprehensive approach that takes into account the history of the disease, its clinical manifestations, data from immunological and instrumental studies, as well as the results of DNA diagnostics. A patient with suspected disease should be examined not only by a neurologist, but also by a dermatologist, otolaryngologist, ophthalmologist, immunologist, pulmonologist, oncologist.
Laboratory diagnosis of ataxia telangiectasia includes a clinical blood test, in which 1/3 of patients have a decrease in the number of lymphocytes. A study of the level of blood immunoglobulins is necessarily carried out, which reveals a significant decrease in IgA and IgE, in 10-12% of IgG cases. In approximately 40% of patients, disease is accompanied by autoimmune reactions, which are evidenced by the presence of autoantibodies to mitochondria, thyroglobulin, and immunoglobulins.
Of the instrumental methods for diagnosing ataxia telangiectasia, the following can be used: ultrasound of the thymus, MRI of the brain, pharyngoscopy, rhinoscopy, lung radiography. With the help of ultrasound, aplasia or hypoplasia of the thymus is diagnosed. MRI of the brain reveals cerebellar atrophy, expansion of the IV ventricle. Lung radiography is necessary for the diagnosis of focal or croup pneumonia, detection of foci of pneumosclerosis and bronchiectatic changes.
Disease should be differentiated from Friedreich’s ataxia, Randu-Osler disease, Pierre-Marie ataxia, Hippel-Lindau disease, etc.
Treatment and prognosis
Unfortunately, effective methods of treating ataxia telangiectasia still remain the subject of search. In modern medicine, it is possible to use only palliative symptomatic treatment of somatic and immunological disorders. The prolongation of the life of patients with Louis-Bar syndrome is facilitated by immunocorregulating therapy with thymus preparations and gamma globulin, vitamin therapy in high dosages and intensive therapy of any infectious process. According to indications, antiviral drugs, broad-spectrum antibiotics, antifungal agents, glucocorticosteroids are used.
Due to the lack of effective treatment methods, disease has an unfavorable prognosis for both recovery and life. Patients with this disease rarely live up to 20 years. In most cases, they die from infectious complications and oncological diseases.