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

Abstract

Abstract Background & Aims In Wilson disease ( WD ), copper accumulates in the liver and other tissues because of mutations in the ATP 7B 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. Methods We included cases with a diagnosis of WD supported by radiocopper testing and later, when available, confirmed by DNA analysis. Incorporation of 64 Cu was measured at 2, 24 and 48 hours following intravenous injection. Diagnostic accuracy (area under the receiver operating characteristic curve [ AUC ]), sensitivity, specificity and predictive value were assessed for 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios and compared with serum measurements of ceruloplasmin, copper, non‐ceruloplasmin‐bound copper and urinary 24‐hours copper excretion. Results Patients having two pathogenic ATP 7B mutations (homozygotes/compound heterozygotes) (n = 74) had significantly lower 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios than heterozygote controls (n = 21) (mean 0.14 and 0.12 vs 0.49 and 0.63, respectively; both P < .001). Of note, 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios had excellent diagnostic accuracy, with AUC s approaching 1, and only 24‐hours urinary copper excretion displayed similar positive features. Other copper metabolism tests studied had lower accuracy, specificity and sensitivity. Conclusions The radioactive copper test had excellent diagnostic accuracy and may be useful in the evaluation of new therapies aimed at restoring ATP 7B function.