A child presents with recurrent pyogenic infections, partial albinism, and peripheral neuropathy. Neutrophils show giant granules on peripheral smear. The molecular defect in Chédiak-Higashi syndrome involves:
- A Deficiency of NADPH oxidase gp91phox subunit preventing oxidative burst
- B Absent CD18 (beta-2 integrin) preventing neutrophil adhesion to endothelium
- C Mutation in LYST (lysosomal trafficking regulator) gene impairing vesicle fusion and causing giant lysosomes in all granule-containing cells ✓
- D Adenosine deaminase deficiency causing lymphocyte apoptosis
Explanation
Chédiak-Higashi syndrome is caused by loss-of-function mutations in LYST (CHS1 gene), encoding a lysosomal trafficking regulator. LYST normally controls membrane fusion and fission events of lysosomes and lysosome-related organelles. In its absence, lysosomes fail to undergo fission after fusion and instead form giant lysosomes visible in neutrophils (impaired degranulation → immunodeficiency), melanocytes (melanosome aggregates → albinism), and neurons (degeneration → neuropathy). NADPH oxidase deficiency is CGD; CD18 deficiency is LAD type 1; ADA deficiency is SCID.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.