Evaluation of clinical and immunological characteristics of patients followed up with the diagnosis of Ataxia Telangiectasia in Hacettepe University İhsan Doğramacı Children's Hospital, Department of Pediatric Immunology

Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive cerebellar degeneration, oculocutaneous telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. The disease may also manifest itself with disorders in various systems such as lymphopenia, high AFP, growth retardation, recurrent infections, endocrine and orthopedic problems. It is included under the title of "Combined Immunodeficiencies with Syndromic Features" in the primary immunodeficiency classification. In our study, the clinical and immunological features of 291 patients with the diagnosis of A-T who were followed up in Hacettepe University İhsan Doğramacı Children's Hospital, Department of Pediatric Immunology between 1980 and 2021 were evaluated retrospectively. 50.9% of the patients were male and 49.1% were female. In 81.9% of the patients, there was a history of consanguinity between the parents, and 51.5% had a family history of A-T. The most frequent application geographical region of the patients is the Central Anatolia region with 43.4%, followed by the Southeastern Anatolia region with 16.8%. The mean age at diagnosis of the patients was 6.35 ± 3.19 years, the mean diagnosis delay was 4.08 ± 2.99 years, and the median follow-up period was 5 years. When the complaints of the patients are examined, the most common reason is unbalanced walking with 95.2%. It is followed by telangiectasia, frequent infections, dysatria and malignancy. When the examination findings of the patients were evaluated, ataxia 97.3%, oculocutaneous telangiectasia 89.7%, dysmetria and dysdiadokinesia 67.7%, dysarthria 40.2%, oculomotor apraxia 40.1%, dystonia or chorea 6.9%, mental retardation 4.1%, endocrine findings 3.4% and orthopedic findings 19.2% were found. In more than half of the patients, both height and weight assessment were below the 10th percentile at the time of diagnosis, and percentile loss continued in the follow-up. There was no increase in the frequency of allergic and autoimmune diseases in this cohort. In our study, malignancy developed in 34 (11.7%) patients during follow-up. The median age at diagnosis of malignancy is 9 (2.5 - 28.75) years. While NHL, ALL, HL are most common under the age of 20, solid tumors are most common over the age of 20. When the brain MRI and brain CT scans of the patients were examined, the most common radiological finding was cerebellar atrophy, which was detected in more than half of the patients. When the thorax CT scans of the patients were evaluated, the most common findings were opacities in 57.8% and bronchiectasis in 42.2%. The most common complete blood count finding was lymphopenia (49.8%). AFP level was found to be high in 98.2% of the patients. While IgA values in 61.8% and IgE values in 45.3% of the patients were found to be lower than the age-appropriate reference ranges, IgG and IgM values were found to be normal in more than half of the patients. While the percentages and absolute values of CD3 in 46.1%, CD4 in 58% and CD19 in 67% of the patients were low, the percentages and absolute values of CD8 and CD16/56 were found to be normal or high in most of the patients. The most common finding in peripheral T and B cell panels is low naive T and naive B cells. Pneumococcal vaccine response was low in 56% of the patients, and anti HBs level was negative in 58.5%. Genetic analysis was performed in 27 patients. Homozygous mutations were detected in 18 patients and compound heterozygous mutations in 9 patients. The most frequently detected mutation is the c.3576 G>A homozygous mutation in the ATM gene located on chromosome 11, which was reported as the most common mutation in the Turkish population in the literature, and was seen in a total of 6 patients from 4 different families in our study. In our study, Ig replacement was given to 44 (15.1%) patients, antimicrobial prophylaxis was given to 76 (26.1%) patients, and antioxidant prophylaxis was given to 89 (30.6%) patients. During the follow-up, 23 (7.9%) patients died. The most common cause of death was malignancy and infections. The mean survival time calculated by the Kaplan Meier method in all patients in our study was found to be 25.55 years and is consistent with the literature data. Close follow-up of patients in terms of nutrition, physical therapy, infections and malignancy will be appropriate. Keywords: ataxia, telangiectasia, primary immunodeficiency