A child presents with giant peroxidase-positive cytoplasmic granules in neutrophils and partial oculocutaneous albinism. Phagocytosis is normal, but intracellular killing of bacteria is impaired. The defective gene encodes a protein involved in:

• A NADPH oxidase assembly
• B Actin cytoskeleton polymerization
• C Lysosomal trafficking regulation ✓
• D Bruton tyrosine kinase (BTK) signaling

Explanation

This is Chediak-Higashi syndrome, caused by mutation in the LYST (CHS1) gene encoding a lysosomal trafficking regulator protein. This causes giant lysosomes (granules) in leukocytes and melanocytes (causing albinism). Phagocytosis is normal but fusion of lysosomes with phagosomes is defective, impairing bacterial killing. NADPH oxidase defect is chronic granulomatous disease; WASP is Wiskott-Aldrich; BTK is X-linked agammaglobulinemia.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.