A patient with Chédiak-Higashi syndrome presents with recurrent pyogenic infections, partial oculocutaneous albinism, and peripheral neuropathy. Peripheral blood smear shows neutrophils with giant azurophilic granules. The molecular defect in this condition affects:

• A NADPH oxidase complex (gp91phox subunit)
• B Myeloperoxidase gene leading to deficient HOCl production
• C Adhesion molecule CD18 causing impaired neutrophil emigration
• D LYST (lysosomal trafficking regulator) gene, causing defective lysosomal fusion ✓

Explanation

Chédiak-Higashi syndrome results from mutation in the LYST gene (chromosome 1q42), encoding a lysosomal trafficking regulator. Defective LYST causes impaired fusion of lysosomes with phagosomes and abnormal organelle trafficking, leading to accumulation of giant, fused lysosomes (azurophilic granules) in neutrophils and melanosomes in melanocytes (explaining albinism). Killing of bacteria is thus impaired despite normal NADPH oxidase function. NADPH oxidase defect causes chronic granulomatous disease; MPO deficiency is usually mild; CD18 mutation causes LAD type I.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.