A national registry for female carriers of chronic granulomatous disease

Registries for inborn errors of immunity can identify the natural history and best practices for these conditions. X-linked chronic granulomatous disease (XLCGD) is an inborn error of immunity characterized by impaired neutrophil oxidative burst, leading to autoimmunity and life-threatening infections. XLCGD carriers can develop similar symptoms and impaired neutrophil function because of skewed X-chromosome inactivation. No registry currently exists for carriers of XLCGD.

To describe findings from the Registry for Autoimmunity and Infections in Chronic Granulomatous Disease Carriers: Surveillance and Evaluation, the first US registry for carriers of XLCGD.

Carriers completed a standardized Research Electronic Data Capture survey capturing demographics, clinical manifestations, laboratory data, and treatment (verified through medical record review when available).

A total of 54 carriers completed the survey between February 2024 and February 2026 (mean age, 46.7 years; range, 1 month-78 years). The mean age at diagnosis was 27.7 years, and the mean diagnostic delay from symptom onset was 14.3 years. There were 43 participants (80%) who reported infectious and/or autoimmune/inflammatory manifestations, with autoimmune/inflammatory conditions (62%) being more common than infections (53%). Dermatologic conditions were frequent early manifestations. The mean dihydrorhodamine (DHR) value was 22% (range, 6%-52%). Among 10 carriers who underwent serial testing, DHR declined by a median of 2.35% annually. Antimicrobial and immunomodulatory therapies were used inconsistently among carriers with CGD-defining infections or DHR values less than 20%.

Analysis of an XLCGD carrier national registry demonstrated that XLCGD carriers experience diagnostic delays and substantial clinical manifestations. Declining DHR suggests progressive neutrophil dysfunction over time in some carriers. These findings highlight the need for symptom monitoring and management strategies for this under-recognized population.