A Large Multicenter Cohort of Ataxia–Telangiectasia: Clinical, Immunologic, Genetic, and Survival Outcomes
Saba Fekrvand, Ayda Firouzabadi, Pouya Vakilipour, Dorsa Safari, Samaneh Delavari, Ali Zarezadeh Mehrabadi, Zahra Chavoshzadeh, Hossein Esmaeilzadeh, Samin Sharafian, Farahnaz DorriMoghaddam, Mahnaz Sadeghi‐Shabestari, Fatemeh Tarighat Monfared, Ehsan Khoshnezhad Afkham, Soheila Aleyasin, Farhad Abolnezhadian, Reza Salyanchi, Hamid Ahanchian, Arash Kalantari, Nasrin Behniafard, Tooba Momen, Roya Sherkat, Marzieh Tavakol, Sahar Barzamini, Alireza Shafiei, Taher Cheraghi, Ahmad Vosughimotlagh, Najmeh Sepahi, Peter Olbrich, Isabelle Meyts, Andrew R. Gennery, Hassan Abolhassani, Nima Rezaei, Reza YazdaniABSTRACT
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.