A 19-year-old woman presents with acute hepatitis (AST 1200 U/L, ALT 980 U/L, ALP 45 U/L — disproportionately low), Coombs-negative haemolytic anaemia, and neuropsychiatric symptoms. Serum ceruloplasmin is 8 mg/dL (low). Kayser-Fleischer rings are absent on slit-lamp examination. Which SINGLE investigation would MOST definitively confirm Wilson's disease in this presentation?
- A 24-hour urine copper > 100 µg/day (or > 40 µg/day in children), confirmed with penicillamine challenge if needed
- B Liver biopsy with quantitative hepatic copper > 250 µg/g dry weight ✓
- C ATP7B gene sequencing showing pathogenic biallelic mutations
- D Serum copper: ceruloplasmin ratio > 5 indicating elevated free copper
Explanation
Liver biopsy with quantitative hepatic copper concentration > 250 µg/g dry weight (normal < 50 µg/g) is the gold standard diagnostic criterion for Wilson's disease when the clinical picture is ambiguous. Kayser-Fleischer rings are absent in up to 50% of patients with hepatic presentation of Wilson's disease (and are almost always present in neurological Wilson's). Serum ceruloplasmin can be low in other liver diseases. 24-hour urine copper is elevated in Wilson's but also in other cholestatic liver diseases and during penicillamine treatment. ATP7B sequencing identifies mutations but there are > 600 mutations described and some remain unclassified (variants of uncertain significance). Hepatic copper quantification provides direct tissue evidence and is considered definitive.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.