Chronic Granulomatous Disease

Etiology
  • Chronic Granuloamtous Disease (CGD) is caused by a defect in NADPH Oxidase, a multi-protein complex which is responsible for the production of Hydrogen Peroxide during the respiratory burst in phagocytes. The respiratory burst exposes ingested bacteria to highly toxic radicals that kill the organisms within the phagosome. Consequently, phagocytic cells such as macrophages and neutrophils cannot properly kill phagocytosed organisms which continue to proliferate unimpeded. Mutations in any one of the subunits of NADPH Oxidase can lead to CGD and thus the pattern of inheritance varies depending on the mutation.
Clinical Consequence
  • Patients with CGD display an infection susceptibility to bacteria, especially with catalase positive organisms such as Staphylococci. Infections with these organisms often results in extensive inflammation likely due to derangement of inflammatory mediators. Because phagocytes cannot kill internalized bacteria, persistent activation of Cell-mediated Immunity likely accounts for the chronic and extensive presence of granulomas in these patients.
Genetics
  • Most cases are X-linked recessive while some are autosomal recessive.