Wilson's disease (hepatolenticular degeneration) is caused by mutations in ATP7B, a copper-transporting P-type ATPase. The biochemical consequence that produces the pathognomonic Kayser-Fleischer rings in the cornea is:

• A Deficient ceruloplasmin synthesis leading to copper deficiency
• B Defective biliary copper excretion leading to copper accumulation in liver, brain, and Descemet's membrane ✓
• C Excess copper absorption through intestinal ATOX1 transporters
• D Copper-induced free radical generation destroying Bowman's layer of the cornea

Explanation

ATP7B normally transports copper into the trans-Golgi network for: (1) incorporation into ceruloplasmin and (2) biliary excretion. In Wilson's disease, impaired biliary excretion causes copper accumulation in the liver (hepatitis, cirrhosis), basal ganglia (neuropsychiatric symptoms), and Descemet's membrane of the peripheral cornea (Kayser-Fleischer rings — golden-brown deposits best seen on slit-lamp). Ceruloplasmin levels are LOW (not high) because copper incorporation into apoceruloplasmin in the Golgi is also impaired. Serum free (non-ceruloplasmin-bound) copper is elevated.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.