Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects.

BACKGROUND A serum ceruloplasmin concentration below 0.20 g/L is conventionally considered as one of the major diagnostic criteria for Wilson disease. This decision threshold has not been fully validated for its diagnostic characteristics, however. In this study, we evaluated various decision thresholds of serum ceruloplasmin concentration in the diagnosis of Wilson disease based on genotype-verified Wilson disease patients, carriers, and normal individuals. METHODS Serum ceruloplasmin concentration was measured by a nephelometric method in 57 Wilson disease patients and 71 family members (49 heterozygotes and 22 wild-type homozygotes), a validation group of 25 subjects clinically suspected of Wilson disease, and 690 normal individuals. We performed ROC analysis using Analyze-it software and confirmed the genotypes by direct DNA sequencing of ATP7B. RESULTS Serum ceruloplasmin concentrations <0.20, 0.14, and 0.10 g/L showed positive predictive values of 48.3%, 100%, and 100%, respectively, and negative predictive values of 98.7%, 97.1%, and 91.9%. In the validation group, a serum ceruloplasmin threshold of 0.14 g/L rendered 100% sensitivity and specificity. Forty of 690 healthy subjects had serum ceruloplasmin concentrations <0.20 g/L; however, these 40 individuals had normal genotypes by DNA sequencing, and none of the 40 had ceruloplasmin concentrations <0.14 g/L. CONCLUSIONS The diagnostic accuracy for Wilson disease using a serum ceruloplasmin concentration of 0.14 g/L as the local decision threshold was better than that using a threshold of 0.20 g/L. We suggest that laboratories providing ceruloplasmin assays determine decision thresholds based on local populations.