Accuracy of the radioactive copper incorporation test in the diagnosis of Wilson disease

city and predictive value were assessed for 24hours/2hours and 48hours/2hours Cu-64 ratios and Background & AimsIn Wilson disease (WD), copper accumulates in the liver and other tissues because of mutations in the ATP7B copper transporter gene. Early and effective anticopper treatment is crucial. However, routine diagnostic methods based on clinical findings, copper metabolism tests, liver biopsies and DNA analyses do not always provide a conclusive diagnosis. The aim was to evaluate radioactive copper incorporation as a diagnostic test. MethodsWe included cases with a diagnosis of WD supported by radiocopper testing and later, when available, confirmed by DNA analysis. Incorporation of Cu-64 was measured at 2, 24 and 48hours following intravenous injection. Diagnostic accuracy (area under the receiver operating characteristic curve [AUC]), sensitivity, specifi compared with serum measurements of ceruloplasmin, copper, non-ceruloplasmin-bound copper and urinary 24-hours copper excretion. ResultsPatients having two pathogenic ATP7B mutations (homozygotes/compound heterozygotes) (n=74) had significantly lower 24hours/2hours and 48hours/2hours Cu-64 ratios than heterozygote controls (n=21) (mean 0.14 and 0.12 vs 0.49 and 0.63, respectively; both P<.001). Of note, 24hours/2hours and 48hours/2hours Cu-64 ratios had excellent diagnostic accuracy, with AUCs approaching 1, and only 24-hours urinary copper excretion displayed similar positive features. Other copper metabolism tests studied had lower accuracy, specificity and sensitivity. ConclusionsThe radioactive copper test had excellent diagnostic accuracy and may be useful in the evaluation of new therapies aimed at restoring ATP7B function.