X-linked agammaglobulinemia (also called X-linked hypogammaglobulinemia, XLA, Bruton type agammaglobulinemia, Bruton syndrome, or Sex-linked agammaglobulinemia) is a rare X-linked genetic disorder discovered in 1952 that affects the body’s ability to fight infection. XLA is an X-linked disorder, and therefore is more common in males. XLA patients do not generate mature B cells, which manifests as a complete lack of antibodies in their bloodstream. B cells are part of the immune system and normally manufacture antibodies (called immunoglobulins), which defend the body from infections by sustaining an immunological humoral antibody response. Patients with untreated XLA are prone to develop serious and even fatal infections. A mutation occurs at the Bruton’s tyrosine kinase (Btk) gene that leads to a severe block in B cell development (at the pre-B to immature B cell stage) and a reduced Immunoglobulin (antibody) production in the serum. Btk is particularly responsible for mediating B cell development and maturation through a signaling effect on the B cell receptor BCR. Patients typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria. It occurs in a frequency of about 1 in 100,000 male newborns, and has no ethnic predisposition. XLA is treated by infusion of human antibody. 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.

XLA is caused by a mutation on the X chromosome of a single gene identified in 1993 which produces an enzyme known as Bruton’s tyrosine kinase, or Btk. XLA was first characterized by Dr. Ogden Bruton in a ground-breaking research paper published in 1952 describing a boy unable to develop immunities to common childhood diseases and infections. It is the first known immune deficiency, and is classified with other inherited (genetic) defects of the immune system, known as primary immunodeficiency disorders.