Chronic granulomatous disease is caused by which defect and leads to susceptibility to which organisms?

• A. Increased NADPH oxidase activity
• B. MPO deficiency
• C. Lack of NADPH oxidase
• D. Complement C3 deficiency

Answer: (C)

The key idea is that phagocytes kill ingested microbes via an oxidative burst powered by NADPH oxidase. This enzyme transfers electrons from NADPH to oxygen to form superoxide, a reactive species that starts a cascade to kill bacteria and fungi. In chronic granulomatous disease, there is a defect in this NADPH oxidase complex, so the respiratory burst cannot occur and neutrophils fail to generate reactive oxygen species effectively. That inability to mount this kill mechanism makes people susceptible to infections with catalase-positive organisms, which can degrade hydrogen peroxide and leave even less substrate for any residual killing. Classic offenders include Staphylococcus aureus, Serratia, Burkholderia cepacia, Nocardia, and Aspergillus. So the defect is the lack of NADPH oxidase, which directly explains both the impaired microbial killing and the characteristic infection pattern. By contrast, increased NADPH oxidase activity would enhance killing; MPO deficiency presents with a different, usually milder susceptibility pattern; and C3 deficiency involves the complement system with a different infection risk.