Chronic granulomatous disease

Rare genetic disease involving 1 in 200,000 people.

Risk of death 1-5% per year.

Inheritance autosomal recessive or X-linked.

Patients with chronic granulomatous disease have deficiencies in generating reactive oxygen species (ROS), are highly susceptible to infection by a number of microbes including Salmonella enterica, Staphylococcus aureus, S2242atia marcescens, and Aspergillus spp.

Disease caused by defects in any one of 5 subunits of phagocyte-derived NADPH oxidase.

Caused by gene changes-missense, nonsense, frameshift, splice or deletion mutations in genes p22, p40, p47, p67 for autosomal disease or gp91vfor X-linked disease.

Defects include: CYBB (65%), CYBA (<5%), NCF1 (30%), NCF2 (<5%), and NCF4.

Subgroups associated with different mortality rates.

Rarely associated with glucose-6-phosphate dehydrogenase.

Associated with neutrophil, monocyte, macrophages, and eosinophil impaired production of superoxide anion and other reactive oxygen intermediates which leads to recurrent infections, granulomatous changes and death.

Survival related to residual reactive oxygen intermediates (Kuhns DB et al).

Residual reactive oxygen intermediate production more predictive of survival than the specific NADPH-oxidase gene mutation.

Even a 1% production of reactive oxygen intermediates confers a survival advantage.

Survival improved by improved antibiotics, use of interferon gamma prophylaxis, and bone marrow transplantation.

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