Chronic Granulomatous Disease - Pathophysiology

Pathophysiology

Phagocytes (i.e., neutrophils, monocytes, and macrophages) require an enzyme to produce reactive oxygen species to destroy bacteria after they ingest the bacteria in a process called phagocytosis, a process known as the respiratory burst. This enzyme is termed "phagocyte NADPH oxidase" (PHOX). The initial step in this process involves the one-electron reduction of molecular oxygen to produce superoxide anion, a free radical. Superoxide then undergoes a further series of reactions to produce products such as hydrogen peroxide (through the action of superoxide dismutase), hydroxyl radical and hypochlorite (bleach - through the action of myeloperoxidase on hydrogen peroxide). The reactive oxygen species this enzyme produces are toxic to bacteria and help the phagocyte kill them once they are ingested. Defects in one of the four essential subunits of this enzyme can all cause CGD of varying severity, dependent on the defect. There are over 410 known possible defects in the PHOX enzyme complex that can lead to chronic granulomatous disease.