Ataxia–Telangiectasia: Immune Findings and Survival

Key Takeaways

• Among Iranian patients with ataxia–telangiectasia, 43.9% first had nonneurologic manifestations.
• Immunoglobulin abnormalities affected 84.7%, and 45.6% had a class-switch recombination defect phenotype.
• Among 45 documented deaths, malignancy accounted for 28.9% and respiratory failure due to respiratory tract infection for 20%.
• Documented malignancy was associated with significantly poorer survival in a small cancer-stratified subset.

Children with ataxia–telangiectasia may come to care with infections or other systemic features before neurologic disease is recognizable. Distinguishing early symptoms from complications that emerge later can be difficult when multiple organ systems are involved. Immune profiles and longer-term outcomes add to that clinical picture. Investigators examined these features in affected patients.

In their European Journal of Neurology study of ataxia–telangiectasia, Fekrvand and colleagues retrospectively examined 305 patients diagnosed or referred through Iran’s national immunodeficiency referral network between 2002 and 2025. The authors report that all 305 met European Society for Immunodeficiencies clinical criteria, although they also describe patients with only nonneurologic manifestations and permitted inclusion based on pathogenic or likely pathogenic variants in the ataxia–telangiectasia mutated (ATM) gene without neurologic findings. Molecular confirmation was available for 124 patients. Clinical and immunologic data came from medical records and registry entries. Investigators classified immunoglobulin phenotypes and used whole-exome sequencing with Sanger confirmation of available variants. Kaplan–Meier survival was measured from diagnosis to death or last documented follow-up, with living patients censored and records lacking sufficient survival information excluded.

Pneumonia was an initial presentation in 13% and was also the most frequently reported infectious complication (30.2%). Respiratory tract infections were recorded in 78% of patients overall; these figures do not establish when subsequent infections developed. Respiratory tract infections differed significantly across immunoglobulin phenotypes, particularly in the hypogammaglobulinemia and class-switch recombination defect groups. Among molecularly confirmed patients, variants classified as severe by predicted molecular effects predominated, and investigators identified previously unreported ATM variants. Survival did not differ significantly by mutation severity, immunoglobulin phenotype, sex, mutation type, or onset group.

Vital status was unknown for 199 of 305 patients, and only 66 had adequate information for the overall Kaplan–Meier analysis. Estimated 10-year survival from diagnosis was 60.2% (95% CI, 43.3%–73.6%). Patients with recorded malignancy had poorer survival in a separate cancer-stratified comparison.

Only eight people with cancer entered the cancer-stratified survival analysis, limiting how precisely its association describes population-wide risk. Missing vital-status records, differing follow-up, and retrospective, nonstandardized assessments restrict generalization beyond the analyzable group. Patients in the overall survival analysis were also more likely to have molecular confirmation than those excluded. Age differences between groups do not establish individual progression. The analysis did not evaluate immunoglobulin replacement, prophylactic antibiotics, or other treatment effects, and its observational associations do not establish causality.

Investigators found that nonneurologic onset and immune dysfunction accompanied a substantial respiratory illness burden in this Iranian cohort. Survival estimates and the cancer-associated difference apply to restricted groups with usable follow-up, not the full cohort.

Clinician Questions

How was a class-switch recombination defect defined in Iranian patients with ataxia–telangiectasia?

Investigators classified this phenotype by increased serum immunoglobulin M together with decreased levels of other switched immunoglobulin subtypes.

What did a severe ATM variant classification indicate in patients with ataxia–telangiectasia?

In this Iranian cohort, severe ATM variant classification reflected predicted molecular consequences under the investigators’ pathogenicity very strong (PVS1) loss-of-function criterion. It was not based on direct tests of ATM protein expression or kinase activity.

This content is intended for healthcare professionals for educational purposes. The article and its image were developed with AI assistance and reviewed by members of the ReachMD team prior to publication. Please refer to the original source linked for the complete and most up-to-date information.