Chediak-Higashi syndrome presents with partial albinism, neuropathy, and recurrent infections due to which defect?

• A. Defect in microtubular function with decreased phagocytosis
• B. Lack of NADPH oxidase
• C. Defect in BTK
• D. IL-12 receptor deficiency

Answer: (A)

Chediak-Higashi syndrome is a lysosomal trafficking disorder caused by a microtubule-based transport defect that disrupts fusion of phagosomes with lysosomes in phagocytes. This impairs intracellular killing, leading to recurrent infections. The same defect also disrupts melanosome transport, causing partial albinism, and affects other cells like neurons, resulting in neuropathy. So a defect in microtubular function with decreased phagocytosis best explains the combination of partial albinism, neuropathy, and recurrent infections.

Lack of NADPH oxidase would cause chronic granulomatous disease with impaired respiratory burst but not albinism or neuropathy. A defect in BTK leads to X-linked agammaglobulinemia with absent B cells and low immunoglobulins, not pigment changes or neuropathy. IL-12 receptor deficiency causes susceptibility to disseminated mycobacterial infections due to impaired Th1 responses, again without pigmentary or neuropathic features.