Clinical features, genotypes, and geographic distribution of 238 Latin American CGD patients

Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI) caused by mutations in genes encoding components of the NADPH oxidase complex, leading to defective microbial killing and increased susceptibility to infections. This study analyzed clinical, genetic, and geospatial data from 238 CGD patients across eight Latin American countries. Genetic variants were identified in 141 patients (59%), with XL-CGD being the most common form (77%). Pneumonia (80%), lymphadenopathy (63%), and skin infections (55.5%) were frequent, with bacteria and fungi, such as Staphylococcus aureus, Aspergillus spp., and mycobacteria, as major pathogens. Antimicrobial prophylaxis was widely used, while IFN-γ was mainly prescribed in Mexico, mainly in cases of classic CGD (XL-CGD). Hematopoietic stem cell transplantation (HSCT) did not improve survival compared to prophylaxis. The leading cause of death was infection, particularly pneumonia and sepsis. XL-CGD patients had worse survival outcomes. The study highlights the need for improved genetic diagnosis, newborn screening, regional treatment guidelines, and expanded access to HSCT.