Outstanding problems of early diagnosis of ataxia-telangiectasia





ataxia-telangiectasia, early diagnosis, children


Background. Ataxia-telangiectasia (AT) is an autosomal recessive multisystem disease characterized by progressive neurological disorders, cerebellar ataxia, telangiectasia, immunodeficiency, increased susceptibility to malignancies, and radiation sensitivity. Neurological manifestations are often the first and dominant in patients with AT. The aim of our study was to identify ways to improve the early diagnosis of ataxia-telangiectasia in children. Materials and methods. The analysis of AT diagnosis in 64 patients from the Ukrainian National Register of Primary Immunodeficiency was performed. Diagnosis of AT was based on clinical symptoms, genetic, and biochemical findings according to the criteria of the European Society for Immunodeficiency. The analysis of clinical signs, complete blood count data, alpha-fetoprotein level, immunoglobulins level and lymphocyte subpopulations was performed in 39 patients with AT based on the questionnaires filled in by immunologists. Results. AT was diagnosed at an average age of 6.2 years, ranging from 1 to 16 years. The average age of delay in diagnosis was 5.0 years. Ataxia was observed in all patients and 87.7 % of children experienced it as the first clinical sign of the disease. The mean age of ataxia onset was 16.4 months. Among other neurological manifestations, dysarthria (84.6 %), oculomotor apraxia (74.4 %), and nystagmus (41 %) were observed. Within the examination, 61.5 % of children lost the ability to walk. At the age of 6 to 12 years, children needed a wheelchair, the average age was 7.9 years. Difficulty swallowing, intentional tremor, and myoclonus were less frequently observed. Cerebellar atrophy or hypoplasia on MRI was found in 33.3 % of patients. The average age of detection of these changes was 10 years. Other signs of AT were as follow: telangiectasia (100 %), recurrent sinopulmonary infections (82.1 %), malignancies (20.5 %) usually manifested later. Among the laboratory findings in children with AT, lymphopenia (71.8 %), an elevated level of alpha-fetoprotein (92.3 %), decreased levels of immunoglobulin A (82.1 %), increased levels of immunoglobulin M (59 %), and a decrease in lymphocytes subpopulations, mainly of CD4 (75.9 %) were observed most often. Conclusions. The presence of ataxia in a child of the second year of life requires the exclusion of ataxia-telangiectasia. The serum alpha-fetoprotein levels should be determined in all children with ataxia. In the case of elevated levels of alpha-fetoprotein, as well as in the presence of frequent sinopulmonary infections, lymphopenia, the children should be referred to an immunologist. The immunologic investigation to determine the immunoglobulins levels and lymphocyte subpopulations may be helpful in AT diagnosing. A timely diagnosis of the disease will prevent polypharmacy, avoid the prescription of unnecessary examinations that may harm the patient, prescribe adequate therapy to prevent infectious complications, which will improve the quality and expectancy of the life of patients with AT.


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Original Researches