A 25-year-old man has progressive neurological symptoms (dysarthria, tremor, psychiatric changes), hepatic dysfunction, and Kayser-Fleischer rings on slit-lamp. Serum ceruloplasmin is 8 mg/dL (low) and 24-hour urine copper is 280 µg/day (elevated). Which finding in Wilson's disease is most sensitive for the diagnosis when ceruloplasmin is normal?
- A KF rings alone are pathognomonic even without low ceruloplasmin
- B Serum free copper (non-ceruloplasmin-bound) > 50 µg/dL
- C Liver copper content on biopsy > 250 µg/g dry weight is the most sensitive test ✓
- D ATP7B gene sequencing showing homozygous H1069Q mutation
Explanation
Liver biopsy copper quantification (> 250 µg/g dry weight) is the gold standard and most sensitive test for Wilson's disease, particularly when ceruloplasmin is normal (occurs in ~5-15% of Wilson's patients) or in acute liver failure where ceruloplasmin may be falsely elevated as an acute phase reactant. Serum free copper > 50 µg/dL and 24-hour urine copper > 100 µg/day are supportive. KF rings are absent in ~50% of hepatic-predominant Wilson's and are not always pathognomonic (can occur in cholestatic liver diseases). ATP7B mutation analysis is useful but multiple mutations exist and not all are identified.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.