agammaglobulinemian

An agammaglobulinemian is a person affected by agammaglobulinemia, a primary immunodeficiency characterized by very low or absent serum immunoglobulins due to impaired B cell development. The term is uncommon in formal medical usage; the condition is more widely known as X-linked agammaglobulinemia (XLA) or agammaglobulinemia.

Pathophysiology involves failure of B cell maturation. In classic XLA, mutations in the BTK gene disrupt B cell development beyond the pre-B cell stage, resulting in markedly reduced or absent circulating CD19+ B cells and very low levels of all immunoglobulin isotypes (IgG, IgA, IgM). T cell numbers and function are typically preserved, and phagocyte or complement function is usually normal.

Genetics and epidemiology: X-linked agammaglobulinemia predominantly affects males, with autosomal recessive forms reported for other gene defects such as IGHM, CD79A/B, and BLNK. The condition is rare, with estimated incidences around 1 in 200,000 to 400,000 births.

Clinical features: Symptoms commonly begin after maternal IgG wanes (about 6 months), with recurrent sinopulmonary infections, otitis media, pneumonia, and sinusitis. Chronic diarrhea and poor responses to vaccines are also seen. Without treatment, structural lung damage and bronchiectasis may develop.

Diagnosis: Suspected from very low serum immunoglobulins (IgG, IgA, IgM) and absent/low B cells on flow cytometry. Genetic testing identifies BTK mutations (or other gene defects). Evaluation of antibody responses to vaccines supports the diagnosis.

Management and prognosis: Lifelong immunoglobulin replacement therapy (IVIG or SCIG) reduces infections. Prompt antibiotic treatment of infections and avoidance of live vaccines are advised. With therapy, life expectancy improves, though chronic lung disease remains a risk.

See also: Bruton's tyrosine kinase; primary immunodeficiency; X-linked agammaglobulinemia.