A 45-year-old presents with jaundice, kayser-Fleischer rings, and elevated liver enzymes. Liver biopsy shows periportal copper deposition by rhodanine stain and hepatocyte ballooning with Mallory-Denk bodies. The fundamental molecular defect in Wilson's disease is:

• A Mutation in ATP7B, impairing biliary copper excretion and copper incorporation into ceruloplasmin ✓
• B Absence of ceruloplasmin production by the liver
• C Excess intestinal copper absorption due to DMT1 mutation
• D Deficiency of metallothionein binding protein

Explanation

Wilson's disease is caused by mutations in ATP7B encoding a P-type ATPase copper transporter in hepatocytes. The defective protein cannot excrete copper into bile or incorporate it into ceruloplasmin, leading to copper accumulation in hepatocytes, brain (basal ganglia), and Descemet's membrane (Kayser-Fleischer rings). Ceruloplasmin is reduced but its deficiency is secondary; DMT1 mutations cause iron overload; metallothionein is a copper-binding protein but its mutation does not cause Wilson's.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.