A 3-year-old boy has recurrent pyogenic infections with Staphylococcus aureus and Aspergillus. Neutrophils show normal chemotaxis but fail to kill intracellular organisms. NBT (nitroblue tetrazolium) test is negative. Flow cytometry of CD18 and CD11b expression is normal. Which gene defect is most likely responsible?

• A ITGB2 (CD18) deficiency — leukocyte adhesion deficiency type I
• B RAC2 gain-of-function mutation — causing neutrophil dysfunction and immunodeficiency
• C MPO deficiency — myeloperoxidase deficiency with impaired neutrophil killing
• D CYBB (gp91phox) — X-linked chronic granulomatous disease (CGD) with absent NADPH oxidase superoxide generation ✓

Explanation

The clinical picture of recurrent catalase-positive organism infections (S. aureus, Aspergillus, Nocardia), negative NBT test (unable to reduce yellow NBT to blue formazan due to absent ROS production), and normal CD18/CD11b (ruling out LAD-I) describes X-linked chronic granulomatous disease (CGD) due to CYBB mutations encoding gp91phox, the catalytic subunit of NADPH oxidase. NADPH oxidase (NOX2) generates superoxide essential for the respiratory burst. MPO deficiency results in partial killing failure (NBT positive, as NADPH oxidase is intact) and is usually asymptomatic.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.