X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body's ability to fight infection.

[3] XLA is deemed to have a relatively low incidence of disease, with an occurrence rate of approximately 1 in 200,000 live births[4] and a frequency of about 1 in 100,000[5] male newborns.

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.

[3] XLA is caused by a mutation on the X chromosome (Xq21.3-q22) of a single gene identified in 1993 which produces an enzyme known as Bruton's tyrosine kinase, or Btk.

[3] 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.

The Btk enzyme plays an essential role in the maturation of B cells in the bone marrow, and when mutated, immature pro-B lymphocytes are unable to develop into pre-B lymphocytes, which normally develop into mature (naive) B cells that leave the bone marrow into the blood stream.

[citation needed] The disorder is inherited in an X-linked recessive fashion (as the gene linked to it is on the X chromosome) and is almost entirely limited to the sons of asymptomatic female carriers.

[citation needed] XLA diagnosis usually begins due to a history of recurrent infections, mostly in the respiratory tract, through childhood.

Results of a genetic blood test confirm the diagnosis and will identify the specific Btk mutation,[3] however its cost prohibits its use in routine screening for all pregnancies.

[citation needed] The most common treatment for XLA is an intravenous infusion of immunoglobulin (IVIg, human IgG antibodies) every week, for life.

Furthermore, it is not known if active vaccines in general have any beneficial effect on XLA patients as they lack normal ability to maintain immune memory.

XLA patients, however, are apparently immune to the Epstein-Barr virus (EBV), as they lack mature B cells (and so HLA co-receptors) needed for the viral infection.

Agammaglobulinemia (XLA) is similar to the primary immunodeficiency disorder Hypogammaglobulinemia (CVID), and their clinical conditions and treatment are almost identical.

These mice have a mutated version of the mouse Btk gene, and exhibit a similar, yet milder, immune deficiency as in XLA.