Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Bruton's Agammaglobulinemia (XLA) [D80.0]

OMIM numbers: 300755300300 (BTK)

Dr. rer. nat. Barbara Bangol, Dr. med. Imma Rost

Scientific Background

XLA (incidence approx. 1:100,000) is a primary humoral immunodeficiency disease that is based on a B cell maturation defect. Clinical signs and symptoms occur between the 4th and 12th month of life and include severe bacterial infections (such as otitis media, pneumonia, meningitis, sepsis), especially due to encapsulated bacteria. One of the most common infections is chronic sinusitis. Although the immune defence against viral infections is generally not impaired, the patients are prone to enterovirus infections. Some suffer from chronic infections such as dermatomyositis or meningoencephalitis; approximately 20% develop arthritis. The B cell maturation defect manifests in a massive decrease in B cells, an almost complete lack in plasma cells and immunoglobulins of all isotypes. The number and functioning of T lymphocytes are normal. Small or lacking tonsills, adenoids and lymph nodes despite the high number of infections may raise suspicion during clinical examination. Treatment involves the administration of immunoglobulins as well as antibiotics according to the particular pathogen spectrum. Complications predominantly include chronic pulmonary disease as well as an increased risk for colorectal cancer and lymphoreticular malignancies.

XLA is caused by mutations in the BTK gene, which is located on the X chromosome and is expressed in all hematopoietic cell lines (except T lymphocytes and plasma cells). There is no clear genotype phenotype correlation; clinical variability may occur within one family. Obligate female carriers show a non-random X-inactivation in their B cells.