1090 Presenting features of patients with ataxia-telangiectasia (A-T): a scoping review

Background Ataxia-telangiectasia (A-T) is a rare autosomal recessive, progressive, multi-system disease caused by mutations in the ataxia-telangiectasia mutated (ATM) gene on chromosome 11q.26. There are 2 types of A-T; the more severe phenotype of classical A-T with a complete absence of ATM protein kinase, and the milder phenotype of variant A-T in which there is some residual protein kinase activity. A-T has a wide spectrum of manifestations including cerebellar ataxia, movement disorders, ocular telangiectasia, recurrent infections, and an increased risk of malignancy. Although textbook narratives exist describing the clinical features of A-T, no attempt has been made to collate the available information to give a complete picture of the presenting features of this rare disease. Objectives To describe the presenting features of A-T and determine any difference in presenting features between classical and variant A-T. Methods 17 searches were carried out in each of 5 databases (Ovid SP (Medline), EMBASE, Web of Science, PubMed, Scopus). The Cochrane Library was also searched. The search protocol is available. The inclusion criteria were all dates, all languages, all ages, human subjects, and clinical relevance. The exclusion criteria were: no reference to A-T within the article, not an original article, animal studies, article not clinically relevant. Results Search returned 194,890 articles; 14,622 titles and abstracts were reviewed after removing 180,268 duplicates. Full text review of 1,163 articles was performed and 1,039 studies were included (13,459 exclusions, 124 excluded after full text review). The presenting symptoms (first symptom) were reported in 1209 cases with a total of 1702 signs or symptoms included. The most common presenting complaint reported was an abnormal gait (n=931), followed by recurrent infections (n=223), speech difficulties (n=113) and movement disorder and other co-ordination difficulties (n=69). Cerebellar ataxia was the most common pattern of abnormal gait. Although cerebellar ataxia was the most common first presenting feature, chronologically we found other symptoms that presented at an earlier age included recurrent infections and other neurological signs and symptoms. The age of onset of presenting symptoms will be presented in more detail. The median age of diagnosis for classical A-T was 6 years (IQR 3 – 9 years) and for variant it was much later in life with a median age of 30 years 6 months (IQR 19.25–40.25 years). Conclusions A-T has a wide variety of presenting features which is further complicated by a wide difference in the age of diagnosis of between classical and variant A-T. The most common presenting feature was an abnormal gait of which cerebellar ataxia was the most common pattern. However other symptoms appear to present earlier including telangiectasia and recurrent infections and dystonia in variant A-T. It is hoped that by developing a better understanding of the spectrum of presenting features of A-T may reduce the age of diagnosis of both forms of A-T.