An 8-month-old boy presents with hypotonia since birth, golden-brown rings at the periphery of the iris on slit-lamp examination, liver disease, and haemolytic anaemia. Serum ceruloplasmin is low and 24-hour urine copper is markedly elevated. The molecular defect in Wilson's disease involves:
- A Mutation in ATP7B gene encoding a copper-transporting P-type ATPase, impairing biliary copper excretion ✓
- B Defective lysosomal copper export leading to intralysosomal copper accumulation
- C Deficiency of metallothionein, the copper-binding protein, causing cytosolic copper toxicity
- D Mutation in COMMD1 gene impairing copper import across the hepatocyte basolateral membrane
Explanation
Wilson's disease is caused by mutations in ATP7B, which encodes a copper-transporting P-type ATPase located in hepatocyte trans-Golgi network and canalicular membrane. Normally, ATP7B incorporates copper into ceruloplasmin and mediates biliary excretion of excess copper. When ATP7B is non-functional, copper accumulates in hepatocytes, eventually spilling into the circulation and depositing in the brain (basal ganglia), eyes (Kayser-Fleischer rings), and kidneys. This is autosomal recessive. COMMD1 (MURR1) mutations cause the similar canine copper toxicosis but not human Wilson's disease.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.