X-linked Agammaglobulinemia

Definition

X-linked agammaglobulinemia (XLA) or Bruton's agammaglobulinemia is present at birth (congenital) and is characterized by low or completely absent levels of immunoglobulins in the bloodstream. Immunoglobulins are protein molecules in blood serum that function like antibodies. Without them, the body lacks a fully functioning immune system. Persons with XLA are vulnerable to repeated, potentially fatal bacterial infections.

Description

XLA occurs in one in 50,000 to one in 100,000 newborns. Almost all persons with the disorder are males. Although persons with XLA carry the genes to produce immunoglobulins, a genetic defect on the X chromosome prevents their formation. This defect is not associated with the immunoglobulins themselves, but rather with the B cells in the bloodstream that ordinarily secrete the immunoglobulins.

B cells are a type of white blood cell. They are the sole producers of immunoglobulins in the body. B cells are produced in the bone marrow and carried to the spleen, lymph nodes, and other organs as they mature. The maturation process depends on an enzyme called Bruton's agammaglobulinemia tyrosine kinase (Btk). If Btk is missing or defective, the B cells cannot mature and cannot produce immunoglobulins.

The gene for Btk is on the X chromosome. Certain changes (mutations) in this gene result in defective Btk. Since the gene is carried on the X chromosome, XLA individuals are almost always male. Females have two X chromosomes, which means they have two copies of the Btk gene, one of which is normal. Males have only one X chromosome.

Causes and symptoms

XLA is caused by a defect in the gene that codes for Btk. This defect leads to blocked maturation of B cells, the cells that produce immunoglobulins. Because other portions of the immune system are functional, people with XLA can fight off some types of infection, such as fungal and most viral infections. Immunoglobulins, however, are vital to combat bacterial infections. Infants with XLA usually do not show symptoms during the first six months of life because immunoglobulins from their mothers are circulating in their bloodstreams. As the mother's supply decreases, the baby becomes increasingly vulnerable to bacterial infections.

Common symptoms of immunoglobulin deficiency appear after the infant is six months old. They include frequent ear and sinus infections, pneumonia, and gastroenteritis. Certain viruses, such as hepatitis and polio viruses, can also pose a threat. Children with XLA grow slowly, have small tonsils and lymph nodes, and may develop chronic skin infections. Approximately 20% of these children develop arthritis, possibly as a result of joint infections.

Content licensed from:

Author Info: Julia Barrett, The Gale Group Inc., Gale, Detroit, Gale Encyclopedia of Medicine, 2002

This feature is for informational purposes only and should not be used to replace the care and information received from your healthcare provider. Please consult a healthcare professional with any health concerns you may have.