Wilson's disease presents with hepatic, neuropsychiatric, and ophthalmologic features. Which investigation is most sensitive for confirming the diagnosis in a patient with equivocal ceruloplasmin and KF rings?
- A 24-hour urine copper (basal and after D-penicillamine challenge)
- B Liver copper quantification on biopsy (>250 µg/g dry weight is diagnostic) ✓
- C Serum copper level alone
- D ATP7B gene mutation analysis by next-generation sequencing
Explanation
Liver biopsy with quantitative copper measurement (hepatic copper >250 µg/g dry weight, normal <50 µg/g) is the most definitive diagnostic test for Wilson's disease, particularly when serum ceruloplasmin is normal (in 5–10% of Wilson's patients) or KF rings are absent (absent in ~50% of those with hepatic presentation). Basal 24-hour urine copper >100 µg/day supports the diagnosis, and the D-penicillamine challenge (>1600 µg/24h post-chelation) is used in children. ATP7B genetic testing identifies causative mutations in >98% but is limited by >600 known mutations, making it confirmatory rather than the primary test.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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