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

. 2022 Mar 15;17(3):e0264177.
 doi: 10.1371/journal.pone.0264177. eCollection 2022.

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

Emily Petley1, Alexander Yule2, Shaun Alexander1, Shalini Ojha13, William P Whitehouse14
Affiliations 

Affiliations

  • 1School of Medicine, University of Nottingham, Nottingham, United Kingdom.
  • 2United Lincolnshire Hospitals NHS Trust, Lincoln, United Kingdom.
  • 3Children's Hospital, University Hospitals of Derby and Burton, NHS Foundation Trust, Derby, United Kingdom.
  • 4Nottingham Children's Hospital, Nottingham University Hospital NHS Trust, Nottingham, United Kingdom.
    • PMID: 35290391
  Free article

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.