A 14-year-old boy with angiokeratomas, episodes of burning pain in the hands and feet, and corneal opacities develops proteinuria. Renal biopsy electron microscopy shows concentric lamellated myelin-like inclusion bodies (zebra bodies) within podocyte lysosomes. What is the underlying defect?

• A Deficiency of galactocerebrosidase leading to accumulation of galactocerebroside
• B Deficiency of sphingomyelinase leading to accumulation of sphingomyelin
• C Mutation of the LMX1B transcription factor causing abnormal GBM development
• D Deficiency of alpha-galactosidase A leading to accumulation of globotriaosylceramide ✓

Explanation

Fabry disease is an X-linked lysosomal storage disorder caused by alpha-galactosidase D deficiency, producing globotriaosylceramide accumulation in podocytes and other cells. Zebra bodies on electron microscopy are the classic renal finding, and the systemic features of angiokeratomas, acroparesthesias, and corneal changes complete the picture. Sphingomyelinase deficiency causes Niemann-Pick disease, and galactocerebrosidase deficiency causes Krabbe 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.