A 9-month-old infant presents with irritability, progressive spasticity, and regression of motor milestones. MRI shows diffuse white matter changes. Enzyme assay reveals deficiency of galactocerebrosidase (galactosylceramidase). Accumulation of which toxic metabolite is chiefly responsible for the destruction of oligodendrocytes seen in this disorder?
- A Sulfatide
- B Glucosylceramide
- C Psychosine ✓
- D Ceramide trihexoside
Correct answer: C. Psychosine
Explanation
Krabbe disease results from galactocerebrosidase deficiency. The accumulated galactosylceramide itself is relatively inert, but psychosine (galactosylsphingosine), a minor metabolite normally cleared by the same enzyme, builds up and is directly cytotoxic to oligodendrocytes, causing demyelination and multinucleated globoid macrophages on biopsy. Sulfatide points to arylsulfatase A deficiency, glucosylceramide to Gaucher disease, and ceramide trihexoside to Fabry disease.
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.