Genetics and immunopathology of chronic granulomatous disease

Chronic granulomatous disease (CGD) is a primary immunodeficiency syndrome characterized by a greatly increased susceptibility to severe fungal and bacterial infections. CGD results from a failure of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme in the patient's phagocytes to produce superoxide. It is caused by mutations in any of four genes that encode the components of the NADPH oxidase. Investigation of CGD patients has identified the different subunits and the genes encoding them. Study of rare CGD variants has highlighted sequences involved in the structural stability of affected components or has provided valuable insights into their function in the oxidase activation mechanism. Functional and molecular CGD diagnosis tests are discussed in this review. Long-term antibiotic prophylaxis has been essential in fighting infections associated with CGD, but approaches based on hematopoietic stem cell transplantation and gene therapy offer great hope for the near future.