Serum ceruloplasmin oxidase activity is a sensitive and highly specific diagnostic marker for Wilson's disease

Abstract

Background/aims: A low serum ceruloplasmin concentration is considered diagnostic for Wilson's disease. We aimed to evaluate an enzymatic test for ceruloplasmin oxidase activity and to compare it with the routinely used immunological ceruloplasmin measurement.

Methods: Serum ceruloplasmin was measured enzymatically with o-dianisidine dihydrochloride as substrate and immunologically. 110 Wilson's disease patients, 52 healthy controls, and 51 patients with impaired liver function not due to Wilson's disease were analyzed. Assay performance was tested by receiver operating characteristic curve analysis, McNemar test, and Spearman's rank correlation.

Results: The greatest sum of sensitivity and specificity was seen for the enzymatic ceruloplasmin assay at a cut-off point of 55 U/L (93.6% and 100%, respectively) and for the immunologic assay at a cut-off point of 0.19 g/L (93.6% and 78.8%, respectively). For healthy controls, the differences in specificity between both assays were statistically significant (McNemar, p=0.02). When additionally including patients with impaired liver function into the control group the specificity declined to 84.5% for the enzymatic assay and to 68.9% for the immunologic assay. The correlation between the enzymatic and immunologic assay was high in healthy controls (r=0.94), but weaker in Wilson's disease patients (r=0.70) and patients with impaired liver function not due to Wilson's disease (r=0.65).

Conclusions: For the enzymatic assay the best cut-off point for predicting Wilson's disease was estimated to be 55 U/L. Our data suggest that the enzymatic ceruloplasmin assay is superior to the immunologic assay in diagnosing Wilson's disease and should become the preferred method.