A 25-year-old woman with Wilson's disease has liver cirrhosis and Kayser-Fleischer rings. The primary metabolic defect is impaired:

• A Biliary excretion of copper due to defective hepatic copper-transporting ATPase ATP7B ✓
• B Intestinal absorption of copper due to defective copper transporter ATP7A
• C Ceruloplasmin synthesis causing excess free copper in plasma
• D Metallothionein-mediated hepatic copper sequestration

Explanation

Wilson's disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by loss-of-function mutations in ATP7B, a hepatocyte copper-transporting P-type ATPase located in the trans-Golgi network. ATP7B normally mediates both incorporation of copper into apoceruloplasmin and excretion of excess copper into bile. Its deficiency causes copper accumulation in the liver (cirrhosis), brain/basal ganglia (neuropsychiatric symptoms), and cornea (Kayser-Fleischer rings, a pathognomonic finding). Treatment with d-penicillamine chelates excess copper for urinary excretion.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.