X-Linked Agammaglobulinemia (XLA)

X-Linked Agammaglobulinemia (XLA)

Antibodies (red) and immune cells (purple).
Credit: NIAID

XLA is an inherited immune disorder caused by an inability to produce B cells or the immunoglobulins (antibodies) that they make. The mutated gene responsible for XLA (Bruton tyrosine kinase or BTK) is located on the X chromosome.

XLA is an X-linked recessive disease. Because males only have one X chromosome, they are affected if they inherit an X chromosome containing mutated BTK.

XLA is also called by these names:

• Bruton type agammaglobulinemia
• X-linked infantile agammaglobulinemia
• Congenital agammaglobulinemia

Causes

XLA is caused by mutations in the BTK gene found on the X chromosome. This gene normally produces a protein that is required for the development of B cells.

Signs and Symptoms

Infants with XLA develop frequent infections of the ears, throat, lungs, and sinuses. Serious infections also can develop in the bloodstream, central nervous system, skin, and internal organs. These children tend to cope well with most short-term viral infections but are very susceptible to chronic viral infections such as hepatitis and polio.

They usually lack or have very small tonsils.

Diagnosis

People with XLA have extremely low numbers of B cells, and blood tests will show extremely low levels of all types of immunoglobulins (antibodies). People with XLA fail to develop antibodies to specific germs and will not produce protective antibodies after immunizations. Most laboratories can examine B cell numbers in blood samples, while specialized labs can test for the BTKmutation.

Treatment and Research

People with XLA receive intravenous (through the vein) or subcutaneous (just under the skin) immunoglobulin regularly and antibiotics to treat infections.

NIH researchers have improved methods to identify the specific microbes responsible for infections in people with XLA. By identifying hard-to-detect bacteria, physicians can prescribe the correct treatments.