A Large Multicenter Cohort of Ataxia–Telangiectasia: Clinical, Immunologic, Genetic, and Survival Outcomes

BACKGROUND: Ataxia telangiectasia (AT) is a life-threatening multisystem disorder characterized mainly by neurologic manifestations, infections, and malignancy. We aimed to present a comprehensive analysis of demographic, clinical, immunologic, and genetic features and outcomes of patients with AT in Iran. METHODS: We conducted a retrospective cohort study of 305 registered patients with AT enrolled through a national referral network (2002-2025). Diagnosis was established according to the European Society for Immunodeficiencies criteria. RESULTS: Mean age at diagnosis and mean age at onset were 72.0 (±46.0) and 25.2 (±35.57) months, respectively. A substantial proportion of patients presented with non-neurological manifestations as their first clinical feature (43.9%). Among non-neurological manifestations, pneumonia was the second most common initial manifestation (13%) and the most frequent infectious complication (30.2%). Variants classified as severe under the predicted loss-of-function (PVS1) criteria were identified in 104 patients, representing 83.8% of those who underwent genetic evaluation. Immunoglobulin abnormalities were detected in 84.7% of patients. A notable proportion of patients showed class switching recombination defects (45.6%), which were associated with a higher burden of clinical morbidity. Median age at death was 12.8 years (95% CI, 11.0-15.0), and the estimated overall survival rates at 5 and 10 years were 81.6% and 60.2%, respectively. Malignancy (28.9%) and respiratory tract infections (20.0%) were the most common causes of death, respectively. CONCLUSION: This large national cohort provides a comprehensive characterization of the clinical, immunologic, and genetic landscape of AT and its determinants of outcome, thereby improving diagnostic recognition, risk stratification, and patient management.

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Journal
European Journal of Neurology
Published
2026-11-01
DOI
https://doi.org/10.1111/ene.70810
Primary Topic
Immunodeficiency and Autoimmune Disorders
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article
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article

A Large Multicenter Cohort of Ataxia–Telangiectasia: Clinical, Immunologic, Genetic, and Survival Outcomes

Farhad Abolnezhadian, Taher Cheraghi, Mahnaz Sadeghi‐Shabestari, N Kalantari et al.
European Journal of Neurology
Immunodeficiency and Autoimmune Disorders
article

A Large Multicenter Cohort of Ataxia–Telangiectasia: Clinical, Immunologic, Genetic, and Survival Outcomes

Farhad Abolnezhadian, Taher Cheraghi, Mahnaz Sadeghi‐Shabestari, N Kalantari, Alireza Shafiei, Andrew Richard Gennery, Samaneh Delavari, Hossein Esmaeilzadeh, Reza Yazdani, Marzieh Tavakol, Nima Rezaei, Isabelle Meyts, Nasrin Behniafard, Peter Olbrich, Hassan Abolhassani, Hamid Ahanchian, Pouya Vakilipour, Saba Fekrvand, Tooba Momen, Samin Sharafian, Roya Sherkat, Ahmad Vosughimotlagh, Sahar Barzamini, Najmeh Sepahi, Ali Zarezadeh Mehrabadi, Zahra Chavoshzadeh, Dorsa Safari, Fateme Tarighat Monfared, Ehsan Khosh Nezhad Afkham, Soheila Aleyasin, Farahnaz DorriMoghaddam, Ayda Firouzabadi, Reza Salyanchi
article en

Abstract

BACKGROUND: Ataxia telangiectasia (AT) is a life-threatening multisystem disorder characterized mainly by neurologic manifestations, infections, and malignancy. We aimed to present a comprehensive analysis of demographic, clinical, immunologic, and genetic features and outcomes of patients with AT in Iran. METHODS: We conducted a retrospective cohort study of 305 registered patients with AT enrolled through a national referral network (2002-2025). Diagnosis was established according to the European Society for Immunodeficiencies criteria. RESULTS: Mean age at diagnosis and mean age at onset were 72.0 (±46.0) and 25.2 (±35.57) months, respectively. A substantial proportion of patients presented with non-neurological manifestations as their first clinical feature (43.9%). Among non-neurological manifestations, pneumonia was the second most common initial manifestation (13%) and the most frequent infectious complication (30.2%). Variants classified as severe under the predicted loss-of-function (PVS1) criteria were identified in 104 patients, representing 83.8% of those who underwent genetic evaluation. Immunoglobulin abnormalities were detected in 84.7% of patients. A notable proportion of patients showed class switching recombination defects (45.6%), which were associated with a higher burden of clinical morbidity. Median age at death was 12.8 years (95% CI, 11.0-15.0), and the estimated overall survival rates at 5 and 10 years were 81.6% and 60.2%, respectively. Malignancy (28.9%) and respiratory tract infections (20.0%) were the most common causes of death, respectively. CONCLUSION: This large national cohort provides a comprehensive characterization of the clinical, immunologic, and genetic landscape of AT and its determinants of outcome, thereby improving diagnostic recognition, risk stratification, and patient management.

European Journal of NeurologyVol. 33(11)
Isfahan University of Medical Sciences (IR), Ahvaz Jundishapur University of Medical Sciences (IR), Tabriz University of Medical Sciences (IR), Mashhad University of Medical Sciences (IR), Islamic Azad University, Mashhad (IR), Shiraz University of Medical Sciences (IR), Guilan University of Medical Sciences (IR), Shahid Sadoughi University of Medical Sciences and Health Services (IR), University Hospital Bonn (DE), Universitair Ziekenhuis Leuven (BE), Imam Khomeini Hospital (IR), Namazi Hospital (IR), Universal Scientific Education and Research Network (IR), Children's Medical Center (IR), Instituto de Biomedicina de Sevilla (ES), Great North Children's Hospital (GB), Hospital Universitario Virgen del Rocío (ES), Alborz University of Medical Sciences (IR), Bahrami Hospital (IR), Shahid Beheshti University (IR), Shahid Beheshti University of Medical Sciences (IR), Tehran University of Medical Sciences (IR), Universidad de Sevilla (ES), Newcastle University (GB), University of Guilan (IR), KU Leuven (BE)
Openalex Percentile: Top 18%
Immunodeficiency and Autoimmune Disorders
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