Bruton Agammaglobulinemia

Below you will find more information about Bruton Agammaglobulinemia from Medigest. If you believe that you are suffering from any of the symptoms of Bruton Agammaglobulinemia it is important that you obtain an accurate diagnosis from a medical professional to ensure that you obtain the correct medication or treatment for your condition. There are medical conditions that carry similar symptoms associated with Bruton Agammaglobulinemia and therefore the information provided by Medigest is offered as a guideline only and should never be used in preference to seeking professional medical advice. The information relating to Bruton Agammaglobulinemia comes from a third party source and Medigest will not be held liable for any inaccuracies relating to the information shown.

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.

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.

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.

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.

Discuss Bruton Agammaglobulinemia in our forums

Discuss Bruton Agammaglobulinemia with other members of Medigest in our forums.