Wilson disease (hepatolenticular degeneration) results from mutations in ATP7B, a copper-transporting P-type ATPase. In early hepatic involvement, which ultrastructural organelle finding in hepatocytes is most characteristic on electron microscopy?

• A Endoplasmic reticulum dilation with misfolded copper-bound protein accumulation and aggregation
• B Lysosomal copper deposition appearing as electron-dense granules within secondary lysosomes
• C Nuclear glycogenation with glycogen particles in the nucleoplasm of periportal hepatocytes
• D Mitochondrial pleomorphism with cristae disorganization, intramitochondrial dense deposits, and intramitochondrial glycogen ✓

Explanation

The earliest hepatic ultrastructural change in Wilson disease is mitochondrial pleomorphism — hepatocyte mitochondria show variable size, distorted cristae (blebbing, elongation, concentric membrane inclusions), and intramitochondrial electron-dense deposits (copper accumulation). Intramitochondrial glycogen is also described. These mitochondrial changes precede histologically visible copper accumulation (positive rhodanine/rubeanic acid staining) and reflect the direct toxic effect of excess copper on mitochondrial oxidative phosphorylation. This EM finding is pathognomonic when combined with other clinical evidence.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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