Relative Exchangeable Copper, Exchangeable Copper and Total Copper in the Diagnosis of Wilson Disease

Abstract

Background and Aims

Diagnosing Wilson disease (WD) remains challenging. The exchangeable copper (CuEXC) methodology measures the non-ceruloplasmin-bound copper fraction in serum. Relative exchangeable copper (REC), the ratio of CuEXC to total serum copper (Total Cu), has been proposed as a potential diagnostic biomarker. This study aimed to evaluate the diagnostic performance of these three copper biomarkers in WD.

Methods

CuEXC and Total Cu levels were measured in newly diagnosed treatment-naïve patients with WD (n = 13), treated WD (n = 91), non-Wilsonian hepatic disease (n = 206) and non-Wilsonian acute liver failure (n = 22). REC, CuEXC and Total Cu were compared among groups. Receiver-operating characteristic analyses were performed.

Results

Median REC was significantly elevated among patients with WD compared to all other groups combined (23.6% vs. 4.9%, p < 0.001). The opposite was found for Total Cu (3.5 μmol/L vs. 17.2 μmol/L, p < 0.001). In newly diagnosed patients with WD, median REC was significantly higher than in treated patients (29.1% vs. 21.6%, p = 0.008). The optimal diagnostic cut-off value for REC was ≥ 13.8% (sensitivity 100% and specificity 99.6%) for newly diagnosed patients versus those with non-Wilsonian hepatic disease. For Total Cu, the optimal cut-off was ≤ 7.1 μmol/L (sensitivity 61.5% and specificity 99.1%) for newly diagnosed patients with WD versus those with non-Wilsonian hepatic disease.

Conclusion

Our data support the diagnostic value of REC in WD. The more broadly available Total Cu also demonstrates a strong diagnostic performance and may be useful in initial work-up. We suggest including REC and/or Total Cu in a future revision of the Leipzig score.