X-linked agammaglobulinemia

X-linked agammaglobulinemia (XLA) is a rare genetic disorder that affects the body's ability to fight infection due to the inability to create mature B cells, which produce antibodies. First described in 1952, it is a primary immunodeficiency caused by a mutation on X chromosome (Xq21.3-q22), making it X-linked and therefore much more common in males.

People with XLA are unable to produce an enzyme known as Bruton's tyrosine kinase, or Btk, which helps in the development of mature B cells via the white blood cell formation process. Btk is particularly responsible for mediating development at the pre-B cell to immature B cell stage through a signaling effect on the B cell receptor BCR. This manifests in an absence of proteins called gamma globulins, including antibodies, in the bloodstream, which reduces the body's humoral immunity response.

XLA sufferers typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria. Serious and even fatal infections are common. XLA is deemed to have a relatively low incidence of disease, with an occurrence rate of approximately 1 in 200,000 live births and a frequency of about 1 in 100,000 male newborns. It has no ethnic predisposition. XLA is treated by infusion of human immunoglobulin. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies.