A 3-year-old boy has recurrent severe bacterial infections (Staphylococcus, Klebsiella, Aspergillus, Serratia). His NBT (nitroblue tetrazolium) test is abnormal — neutrophils fail to reduce NBT to blue formazan. Superoxide generation by PMA stimulation is absent. What is the PRIMARY molecular defect?
- A Deficiency of myeloperoxidase (MPO) — unable to generate HOCl from H2O2
- B Deficiency of glucose-6-phosphate dehydrogenase — inability to generate NADPH for the respiratory burst
- C Deficiency of leukocyte adhesion molecule CD18 — inability to migrate to infection site
- D Deficiency of NADPH oxidase complex (most commonly gp91phox encoded by CYBB gene, X-linked) — unable to generate superoxide ✓
Explanation
Chronic granulomatous disease (CGD) results from deficiency of NADPH oxidase, which catalyzes the respiratory burst: NADPH + 2O2 → NADP+ + 2O2•- (superoxide). The most common form is X-linked (gp91phox subunit, encoded by CYBB) accounting for ~65% of cases. Defective superoxide generation means failure to kill catalase-positive organisms (Staphylococcus, Klebsiella, Serratia, Aspergillus, Burkholderia). NBT test (normal neutrophils reduce colorless NBT to purple/blue formazan using NADPH oxidase-generated superoxide) is abnormal in CGD. MPO deficiency causes mild susceptibility to Candida. G6PD-deficiency can cause functional CGD-like picture but is rare. LAD causes recurrent bacterial (not fungal) infections with absent pus formation.
Reference: Ghai Essential Pediatrics, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.