Clinical, immunological and genetic characterization of patients with X-linked agammaglobulinemia in Costa Rica

X-linked agammaglobulinemia is caused by mutations in the gene encoding Bruton tyrosine kinase. It produces an arrest in the maturation and differentiation of B cells with very low levels of all immunoglobulins isotypes. The aim of the study was to characterize the clinical, immunological and genetic defects in patients with XLA in Costa Rica. Sixteen cases were identified over a period of 30 years, a case every 2 years, approximately. Three patients were asymptomatic and diagnosis was made on family history. The average age of onset of symptoms was 1.46 years-old (0.08-6.1). Six patients (44%) had onset of symptoms before 1 year of age and 12 (81%) patients before 5 years of age. The average age of diagnosis was 3.63 years-old (0.17-13, SD 3.51 years-old the average time between the onset of symptoms and the diagnosis was 2.5 years (2.5 months to 12 years, SD 3 years). The initial reason to study the patients was a recurrent infection, family history of XLA, arthritis and neutropenia. Four patients had pneumonia and two had suppurative lung disease. Nine patients had recurrent infections: acute otitis media, sinusitis, mastoiditis and recurrent diarrhoea. Three patients presented with arthritis. Neutropenia as an isolated event was not identified in any case. All patients receive monthly IVIG and no deaths were reported. Three new likely pathogenic/pathogenic variants in BTK gene have been described in our population. This is the first report of XLA Costa Rican patients and their BTK mutations.

Automated summary

This study characterizes the clinical, immunological, and genetic defects in XLA patients in Costa Rica. The study identifies a delay between symptom onset and diagnosis in XLA patients, highlighting the importance of early detection for preventing complications. Additionally, new likely pathogenic/pathogenic variants in the BTK gene were found in this population, providing valuable information for future genetic diagnosis.