Agammaglobulinemia Associated with a Mutation in the TCF3 Gene with Initial Autoimmune Manifestation

Introduction Agammaglobulinemia is an innate immune deficiency (IID) characterized by an alteration in B lymphocyte maturation due to genetic defects. One of the less common causes of this condition is a mutation in the TCF3 gene, which can be transmitted through autosomal dominant or recessive inheritance. This mutation affects the expression of transcription factors essential for B cell development, causing a decrease in peripheral blood and, consequently, severe hypogammaglobulinemia. Case Report An 8-year-old female patient with a history of juvenile idiopathic arthritis diagnosed at age 6 and a history of recurrent respiratory infections since the first year of life, including multiple episodes of pneumonia. In the immunological evaluation, immunoglobulin dosage revealed markedly decreased levels: IgG at 287 mg/dL, IgM <20 mg/dL, and IgA <10 mg/dL. Analysis of lymphocyte subpopulations showed an isolated decrease in B lymphocytes, representing only 1.3% of the total (68 cells/mm3). Genetic testing by sequencing identified a pathogenic variant in the TCF3 gene. Given these findings, treatment with intravenous human immunoglobulin was initiated every three weeks, accompanied by antibiotic prophylaxis. Discussion The TCF3 gene mutation is an IEI of the antibody deficiency group, which is rare, with few cases reported worldwide. It is characterized by recurrent infections during childhood, agammaglobulinemia, growth failure, and in some cases is associated with neoplastic diseases. However, our patient presents with systemic joint disease as the initial presenting symptom accompanying recurrent infections. Due to its varied phenotypic expression, it requires multidisciplinary management for diagnosis and treatment.