Chronic Granulomatous Disease: From Genetic Defect to Clinical Presentation

Chronic granulomatous disease (CGD) is a rare, primary immune deficiency rendering the affected individuals hypersusceptible to bacterial and fungal infections. The underlying defect is an inherited inability of the patients' phagocytes to produce the reactive oxygen species (ROS) that are necessary for the full antimicrobial action of these cells. The ROS are normally produced by a membrane-bound enzyme complex, the NADPH-oxidase. Certain mutations in genes encoding this enzyme result in a nonfunctional oxidase and thereby abrogated ROS production and diminished bactericidal capacity. In addition to increased susceptibility to infection, CGD patients also regularly suffer from a number of different inflammatory complications, such as granuloma formation, inflammatory bowel disease, and lupus-like syndromes. These latter symptoms likely stem from what seems to be a propensity for exaggerated inflammatory reactions.