A National Registry for Female Carriers of Chronic Granulomatous Disease.

Abstract

BackgroundRegistries for inborn errors of immunity (IEI) can identify natural history and best practices for these conditions. X-linked chronic granulomatous disease (XLCGD) is an IEI characterized by impaired neutrophil oxidative burst, leading to autoimmunity and life-threatening infections. XLCGD carriers can develop similar symptoms and impaired neutrophil function due to skewed X-chromosome inactivation. No registry currently exists for carriers of XLCGD.ObjectiveWe describe findings from the Registry for Autoimmunity and Infections in Chronic Granulomatous Disease Carriers: Surveillance and Evaluation (RAISE), the first U.S. registry to carriers of XLCGD.MethodsCarriers completed a standardized REDCap® survey capturing demographics, clinical manifestations, laboratory data, and treatment (verified through medical record review when available).ResultsFifty-four carriers completed the survey between February 2024 and February 2026 (mean age 46.7 years, range 1 month-78 years). Mean age at diagnosis was 27.7 years, and mean diagnostic delay from symptom onset was 14.3 years. Forty-three participants (80%) reported infectious and/or autoimmune/inflammatory manifestations, with autoimmune/inflammatory conditions (62%) more common than infections (53%). Dermatologic conditions were frequent, early manifestations. Mean dihydrorhodamine (DHR) value was 22% (range 6-52%). Among ten carriers with serial testing, DHR declined by a median of 2.35% annually. Antimicrobial and immunomodulatory therapies were inconsistently used among carriers with CGD-defining infections or DHR values <20%.ConclusionAnalysis 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. These findings highlight the need for symptom monitoring and management strategies of this underrecognized population.