X-Linked Agammaglobulinemia of Bruton

Etiology
  • X-linked Agammaglobulinemia of Bruton is caused by an inactivating mutation in the Bruton Tyrosine Kinase gene which is required for rearrangement of the antibody light chain gene during B-cell Development. In consequence, most B-cells do not mature past this point in their development and thus there is a total absence or severe reductions in peripheral mature B-cells and Plasma Cells. Correspondingly, the lymph nodes and Peyer's Patches lack germinal centers and patients display a hypogammaglobulinemia or Agammaglobulinemia affecting all antibody classes. However, Cell-mediated Immunity and T-cell responses are completely intact.
Clinical Consequences
  • The disease only manifests in infancy, once maternally-derived antibodies from breast milk have disappeared from infant plasma after roughly 6 months. Patients display infection susceptibility to pyogenic bacteria such as Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Infections generally center around the sinopulmonary tract and include sinusitis, otitis media, URIs, pneumonia, pharyngitis, and bronchitis which can lead to bronchiectasis. Viral gastritis is also common and thus patients display recurrent infectious diarrhea. Overall, however, host defense against viruses and fungi is largely intact due to fully functional Cell-mediated Immunity; however, patients will suffer from repeated viral and fungal infections due to an inability to develop long-term neutralizing antibodies.
Inheritance
  • Inheritance is X-linked recessive and consequently seen almost exclusively in men.