A 2-year-old child has recurrent infections, partial albinism, silver-gray hair, and large granules in neutrophils and NK cells on peripheral smear. The molecular defect is:

• A Absent NADPH oxidase components causing failure to generate superoxide
• B RAC2 GTPase mutation impairing neutrophil actin polymerization
• C LYST gene mutation causing giant lysosomes and defective phagolysosome fusion ✓
• D CD18 (beta-2 integrin) deficiency preventing neutrophil adhesion and diapedesis

Explanation

Chediak-Higashi syndrome is caused by mutations in the LYST (lysosomal trafficking regulator) gene, leading to giant cytoplasmic granules in neutrophils, NK cells, and melanocytes. Neutrophil killing is impaired because phagolysosomes cannot form normally. Partial albinism results from defective melanosome transport. Chronic granulomatous disease involves NADPH oxidase; LAD involves CD18; RAC2 mutation causes a distinct rare neutrophil dysfunction.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.