The natural history of ataxia-telangiectasia (A-T): A systematic review

Petley, Emily; Yule, Alexander; Alexander, Shaun; Ojha, Shalini; Whitehouse, William P

Abstract

Background: Ataxia-telangiectasia is an autosomal recessive, multi-system, and life-shortening disease caused by mutations in the ataxia-telangiectasia mutated gene. Although widely reported, there are no studies that give a comprehensive picture of this intriguing condition. Objectives: Understand the natural history of ataxia-telangiectasia (A-T), as reported in scientific literature. Search methods: 107 search terms were identified and divided into 17 searches. Each search was performed in PubMed, Ovid SP (MEDLINE) 1946-present, OVID EMBASE 1980 -present, Web of Science core collection, Elsevier Scopus, and Cochrane Library. Selection criteria: All human studies that report any aspect of A-T. Data collection and analysis: Search results were de-duplicated, data extracted (including author, publication year, country of origin, study design, population, participant characteristics, and clinical features). Quality of case-control and cohort studies was assessed by the Newcastle-Ottawa tool. Findings are reported descriptively and where possible data collated to report median (interquartile range, range) of outcomes of interest. Main results: 1314 cases reported 2134 presenting symptoms. The most common presenting symptom was abnormal gait (1160 cases; 188 studies) followed by recurrent infections in classical ataxia-telangiectasia and movement disorders in variant ataxia-telangiectasia. 687 cases reported 752 causes of death among which malignancy was the most frequently reported cause. Median (IQR, range) age of death (n = 294) was 14 years 0 months (10 years 0 months to 23 years 3 months, 1 year 3 months to 76 years 0 months). Conclusions: This review demonstrates the multi-system involvement in A-T, confirms that neurological symptoms are the most frequent presenting features in classical A-T but variants have diverse manifestations. We found that most individuals with A-T have life limited to teenage or early adulthood. Predominance of case reports, and case series demonstrate the lack of robust evidence to determine the natural history of A-T. We recommend population-based studies to fill this evidence gap.

Citation

Petley, E., Yule, A., Alexander, S., Ojha, S., & Whitehouse, W. P. (2022). The natural history of ataxia-telangiectasia (A-T): A systematic review. PLoS ONE, 17(3), Article e0264177. https://doi.org/10.1371/journal.pone.0264177

• Journal Article Type: Review
• Acceptance Date: Feb 6, 2022
• Online Publication Date: Mar 15, 2022
• Publication Date: Mar 1, 2022
• Deposit Date: Mar 15, 2022
• Publicly Available Date: Mar 16, 2022
• Journal: PLoS ONE
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 3
• Article Number: e0264177
• DOI: https://doi.org/10.1371/journal.pone.0264177
• Keywords: Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/7605753
• Publisher URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264177