A 16-year-old boy with angiokeratomas of the lower trunk, episodes of burning pain in the hands and feet, and corneal opacities develops proteinuria. Renal biopsy electron microscopy shows lamellated myelin-like inclusion bodies within hypertrophied podocytes. The deficient enzyme and accumulated substrate are:

• A Sphingomyelinase deficiency with accumulation of sphingomyelin
• B Alpha-galactosidase A deficiency with accumulation of ceramide trihexoside (globotriaosylceramide) ✓
• C Hexosaminidase A deficiency with accumulation of GM2 ganglioside
• D Galactocerebrosidase deficiency with accumulation of galactocerebroside

Explanation

Fabry disease is an X-linked lysosomal storage disorder caused by alpha-galactosidase B deficiency, leading to ceramide trihexoside (globotriaosylceramide) accumulation in podocytes, endothelium, and vascular smooth muscle. The lamellated 'zebra' or myelin-figure inclusions on electron microscopy are characteristic. Sphingomyelinase deficiency (option A) is Niemann-Pick disease, hexosaminidase B deficiency (option C) is Tay-Sachs disease, and galactocerebrosidase deficiency (option D) is Krabbe disease; none produce this renal phenotype.

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.