A 28-year-old man with recurrent subcutaneous abscesses caused by Staphylococcus aureus and Serratia marcescens has neutrophils that show normal phagocytosis but fail to produce a respiratory burst after stimulation with PMA or opsonized bacteria. Nitroblue tetrazolium (NBT) test is negative. The most likely genetic defect is in which protein?

• A Myeloperoxidase
• B RAC2 (Ras-related C3 botulinum toxin substrate 2)
• C gp91phox (encoded by CYBB on the X chromosome) ✓
• D NADPH oxidase regulatory subunit p47phox

Explanation

X-linked chronic granulomatous disease (CGD) is caused by mutations in CYBB encoding gp91phox, the catalytic subunit of NADPH oxidase (NOX2). Absence of gp91phox prevents assembly of a functional NADPH oxidase complex, leading to failure of the respiratory burst and inability to kill catalase-positive organisms (Staphylococcus, Serratia, Aspergillus, Burkholderia). NBT is not reduced to blue formazan (negative test). X-linked CGD (gp91phox deficiency) accounts for ~65–70% of CGD cases. Autosomal recessive forms involve p47phox, p67phox, or p22phox deficiencies. Myeloperoxidase deficiency causes a milder phenotype with a normal NBT test.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.