Wilson's disease (hepatolenticular degeneration) is caused by ATP7B mutation. The biochemical consequence of ATP7B dysfunction that explains both the hepatic and neurological manifestations is:

• A Deficiency of copper-dependent SOD causing oxidative damage to dopaminergic neurons
• B Excess copper competes with zinc for metallothionein binding, causing zinc deficiency
• C ATP7B mutation impairs copper absorption from the duodenum, causing paradoxical systemic copper deficiency
• D Impaired copper incorporation into ceruloplasmin and defective biliary copper excretion, causing copper accumulation in liver, brain, and Descemet membrane ✓

Explanation

ATP7B is a copper-transporting P-type ATPase located in hepatocyte trans-Golgi networks and canalicular membranes. It performs two functions: incorporating copper into apoceruloplasmin (forming ceruloplasmin) and exporting copper into bile for elimination. ATP7B mutation impairs both functions: serum ceruloplasmin falls (ceruloplasmin is produced but without copper is rapidly degraded), and biliary copper excretion fails. Free copper accumulates in hepatocytes (hepatitis, cirrhosis), spills into blood, deposits in basal ganglia (neuropsychiatric), and cornea (Kayser-Fleischer rings at Descemet membrane). ATP7A (Menkes disease) handles intestinal copper absorption, not ATP7B.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.