Clinical and genetic characterization of X-linked agammaglobulinemia in a Colombian cohort

Introduction X-linked Agammaglobulinemia (XLA) is an inborn error of immunity (IEI) caused by mutations in the BTK gene, resulting in the absence of mature B-cells and altered serum immunoglobulin levels. In Colombia, unified epidemiological and genetic data are lacking. This study aims to characterize XLA patients in the country demographically, phenotypically, and genotypically. Methods A multicenter, observational, cross-sectional study based on clinical records. Thirty-eight patients with B-cell counts <2% and hypogammaglobulinemia were included. Clinical, immunological, and genetic variables and outcomes were analyzed using descriptive statistics in R-Studio. Results Thirty-eight males were analyzed, with a median age at diagnosis of 16 months (IQR 7.2–21.8). Genetic testing was available for 84.2% (n = 32), identifying 15 distinct variants, 53% of which were novel. Sinopulmonary infections were the primary manifestation (92.1%), notably pneumonia (42.1%) and otitis media (39.5%). Median baseline IgG levels were 187 mg/dL. Bronchiectasis was documented in 34.2% of cases. The eight-year survival rate was 71.1%. Discussion The Colombian cohort shows a relatively early diagnosis but a high burden of structural sequelae (bronchiectasis), suggesting a need to optimize immunoglobulin replacement therapy. The high proportion of novel genetic variants underscores the importance of regional studies. This study represents the most robust characterization of XLA in Colombia, providing key data to improve clinical suspicion and prognosis.