BrutonTypAgammaglobulinämie

Bruton-type agammaglobulinemia, historically described as Bruton agammaglobulinemia, is an X-linked primary immunodeficiency caused by mutations in the BTK gene on the X chromosome. The BTK gene encodes Bruton tyrosine kinase, a cytoplasmic signaling protein essential for B cell development. Mutations impair signaling required for maturation from pre-B cells to mature B cells, resulting in very low or absent circulating CD19+ B cells and markedly reduced levels of immunoglobulins across all classes, especially IgG, IgA, and IgM. T cell numbers and function are typically normal, so cellular immunity is relatively preserved.

Clinical features usually begin after infancy when maternal IgG wanes, with recurrent bacterial infections of the sinopulmonary tract, otitis media, and pneumonia. Patients may experience chronic or recurrent infections and poor responses to vaccines due to the lack of humoral immunity. Laboratory findings include markedly reduced or absent B cells in peripheral blood and pan-hypogammaglobulinemia. Diagnosis is supported by reduced B cell numbers and low immunoglobulin levels, and is confirmed by identification of pathogenic mutations in BTK through genetic testing.

Management consists of lifelong immunoglobulin replacement therapy (IVIG or SCIG) to maintain protective IgG levels and prevent infections, along with prompt antibiotic treatment of infections. Live vaccines are generally avoided or used with caution, and responses to standard vaccines are typically blunted. Prognosis has improved substantially with immunoglobulin therapy, though untreated disease can lead to recurrent infections and early mortality. Bruton-type agammaglobulinemia is most common in males and is inherited in an X-linked pattern.