A 6-month-old boy presents with recurrent Pseudomonas aeruginosa and Staphylococcus aureus infections, a painful lip ulcer, partial oculocutaneous albinism, and nystagmus. Peripheral blood smear shows giant granules in neutrophils. Which pathological mechanism underlies this immunodeficiency?

• A Defective leukocyte adhesion due to absent CD18 (beta-2 integrin); LAD-I
• B Absent NADPH oxidase leading to failure of oxidative burst; chronic granulomatous disease
• C IL-12 receptor deficiency causing impaired Th1 response and susceptibility to mycobacteria and Salmonella
• D LYST gene mutation causing defective lysosomal trafficking and impaired phagolysosome fusion; Chediak-Higashi syndrome ✓

Explanation

Chediak-Higashi syndrome is caused by autosomal recessive mutations in the LYST gene (lysosomal trafficking regulator), leading to abnormally large lysosomes/granules in all granule-containing cells. In neutrophils, giant azurophilic granules form and phagolysosome fusion is impaired, rendering bacteria-killing defective. Melanocytes have giant melanosomes causing partial albinism. NK cell and CTL function is impaired (leading to HLH/accelerated phase). Giant granules in peripheral blood neutrophils/monocytes are pathognomonic. CGD lacks oxidative burst; LAD lacks CD18; IL-12R deficiency affects mycobacterial/Salmonella killing.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.