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

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.

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.

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.

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.