ILLNESSOPEDIA

Free Online Database Of Diseases, Illnesses & Ailments

  •  


Bruton Agammaglobulinemia



Bruton Agammaglobulinemia Definition


Bruton agammaglobulinemia was the first immunodeficiency disease to be described. Colonel Ogden Bruton noted in 1952 the absence of immunoglobulins in a young male with a history of pneumonias and other bacterial sinopulmonary infections. Bruton was also the first physician to furnish specific immunotherapy for this X-linked disorder by administering intramuscular injections of immunoglobulin G (IgG). The patient improved but died of chronic pulmonary disease in his fourth decade of life. This disorder is now formally known as X-linked agammaglobulinemia (XLA), and the gene defect has been mapped to the gene that codes for Bruton tyrosine kinase (Btk) at band Xq21.3. The BTK gene is big and consists of 19 exons that encode the 659 amino acids that form the Btk cytosolic tyrosine kinase. Mutations can happen in any area of the gene. Btk is needed for the proliferation and differentiation of B lymphocytes. In the absence of working Btk, mature B cells that express surface immunoglobulin and the marker CD19 are few to absent. The lack of CD19 is readily detected with fluorocytometric assays, and this finding usually easily confirms the diagnosis of XLA in a male. As Bruton originally described, XLA shows itself as pneumonias and other bacterial sinopulmonary infections in 80% of cases. Such infections that start in male infants as maternal IgG antibodies, acquired transplacentally, are lost. Thus, XLA is most often diagnosed when unusually severe or recurrent sinopulmonary infections occur in a male infant younger than 1 year.


Bruton Agammaglobulinemia Historical Background


All patients affected with X-linked agammaglobulinemia (XLA) are males. More than 90% of affected males have unusually severe or recurrent sinopulmonary infections. Meningitis, osteomyelitis, sepsis, and gastrointestinal tract infectious (eg, gastroenteritis or diarrhea) are uncommon initial manifestations of this disease.


Bruton Agammaglobulinemia Pathophysiology


In the absence of mature B cells, patients do not have lymphoid tissue and fail to develop plasma cells, the cells that manufacture antibodies. Germinal centers where B cells proliferate and differentiate are poorly developed in all lymphoid tissue, together with the spleen. Tonsils, adenoids, peripheral lymph nodes, and Peyer patches in the intestines are all small or missing. The lungs and the lamina propria of the gut do not have the normal pattern of lymphocyte distribution. However, biopsy of lymphoid tissue and bone marrow examination are not currently done in the workup of most cases of XLA and other forms of hypogammaglobulinemia. Animal models of human BTK mutations are limited to mice at this time. Mouse models have milder disease than those of humans. However, murine models, including knockout and transgenic mice, have been proven useful in understanding the mechanisms of B-cell production, differentiation, and antibody formation. Murine gene mutations in human counterparts may be connected with a clinical illness different from the illness seen in mice.


Bruton Agammaglobulinemia Prevalence


A frequency of 1 case per 250,000 individuals has been estimated in the United States. This number, howver, was reviewed prior to the availability of mutational analysis and is generally considered to be an underestimate. New mutations are believed to cause 30-50% of all XLA cases.


Most Viewed Pages



Recent Searches



Our Visitors Ask About



Medical News