The genetic basis of chronic granulomatous disease

Abstract

Chronic granulomatous disease is a serious clinical entity. The disease is caused by the failure of NADPH oxidase in phagocytic leukocytes to generate superoxide, needed for the killing of micro-organisms. The patients need careful management aimed at prevention and aggressive treatment of infections. CGD is a heterogeneous syndrome, both clinically and genetically. This disease is caused by a diversity of mutations, and multiple genes are affected. In fact, in the A22 and X91 subtypes of CGD, in which the alpha subunit and the beta subunit of cytochrome b558 are affected, respectively, the mutations are virtually unique for each CGD family tested. The results of these studies provide a better understanding of the mechanism of action of the various components of the superoxide-generating enzyme. Although treatment of CGD patients has improved considerably over the past 30 years, death caused by overwhelming infections is still a serious threat. Prenatal diagnosis now provides the relatives of a CGD patient with the possibility to choose for first-trimester abortion of an affected fetus. Moreover, genetic correction of the disease is now a goal within reach.