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

Abstract

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 defect in patients with XLA in Costa Rica. Sixteen cases were identi ed over a period of 30 years, a case every 2 years, approximately. Three patients were asymptomatic and diagnosis was made by 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). Initial reason to study the patients was recurrent infection, family history of XLA, arthritis and neutropenia. Four patients had pneumonia and two had suppurative lung disease. Nine patients had recurrent infection: acute otitis media, sinusitis, mastoiditis and recurrent diarrhea. Three patients presented with arthritis. Neutropenia as an isolated event was not identi ed 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 rst report of XLA Costa Rican patients and their BTK mutations.