agammaglobulinemia

Agammaglobulinemia refers to a group of primary immunodeficiency disorders characterized by very low or absent levels of immunoglobulins in the blood due to impaired development of B cells. The best known form is X-linked agammaglobulinemia (XLA), also called Bruton's agammaglobulinemia, which affects mainly males.

Most cases of XLA are caused by mutations in the BTK gene, which encodes Bruton’s tyrosine kinase. Loss of BTK blocks B cell maturation at the pre‑B cell stage in the bone marrow, leading to very few circulating B cells and markedly reduced immunoglobulin levels. Rare autosomal recessive forms result from mutations in other genes involved in B cell development (for example IGLL1, the lambda5 surrogate light chain component). The clinical picture typically emerges after 6 months of age when maternal antibodies wane, with recurrent sinopulmonary infections due to encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. Some patients also experience otitis media, pneumonia, sinusitis, and gastrointestinal infections.

Laboratory findings include very low or absent IgG, IgA, and IgM, absent or markedly reduced CD19+ B cells, and normal or near-normal T cell numbers and function. Specific antibody responses to vaccines are poor or absent. Diagnosis is confirmed by genetic testing identifying BTK mutations (or mutations in other B cell–related genes).

Treatment consists of lifelong immunoglobulin replacement therapy, given intravenously or subcutaneously, to provide broad antibody protection. Infections are treated promptly; prophylactic antibiotics may be used in some cases. Live vaccines are avoided in affected individuals. With ongoing Ig replacement and infection management, many individuals achieve a normal or near‑normal lifespan and quality of life. Regular follow‑up with immunology specialists is recommended for monitoring and genetic counseling.