Chronic granulomatous disease: a syndrome of phagocyte oxidase deficiencies

Abstract

Chronic granulomatous disease (CGD) is an inherited disorder of host defense due to the inability of the phagocyte to generate toxic oxygen metabolites upon appropriate stimulation. The disorder is heterogeneous even within the confines of a defective respiratory burst oxidase function, and may arise from a biochemical lesion at either the receptor, the activating pathways or the enzyme level. The identification of defects in plasma membrane depolarization, missing cytochrome and abnormal enzymatic function has yielded new insights into the pathophysiologic basis of CGD. A classification of this syndrome based on more precise biochemical criteria is proposed, which defines the disease as distinct from other associated enzymopathies with similar pathology and emphasizes the metabolic basis of the pathophysiologic defect in phagocyte function. Review of the clinical manifestations, pathogenic organisms and natural course of the disease, emphasizes the critical role of the oxidative metabolism of the normal neutrophil and offers a perspective on oxygen free radical biochemistry in the inflammatory response.