The serum concentration of the
copper protein ceruloplasmin has been an important diagnostic
indicator of
Wilson's disease (WD). It is widely quoted that 95% of people with WD have low serum
ceruloplasmin concentrations. Current evidence suggests that a normal serum
ceruloplasmin concentration is more common in patients with WD, particularly those with
liver disease, perhaps in part because of the routine use of an immunologic assay. This assay might indicate a normal level of
ceruloplasmin when the enzymatic activity is lower. Enzymatic activity is the biologically relevant parameter. We compared the immunologic measurement with the enzymatic assessment of
oxidase activity in patients with liver or
neurologic symptoms of unknown origin in whom WD was considered in the differential diagnosis. Although a strong correlation of
ceruloplasmin protein concentration with
oxidase activity was observed in controls, this was not the case for these patients. Twelve patients, presenting with various types of hepatic disease, demonstrated a weak correlation between
ceruloplasmin protein concentration and
oxidase activity. Ten percent of patients with
neurologic symptoms ( n = 41) had low
ceruloplasmin concentrations and
oxidase activity, and another 8% had normal
ceruloplasmin concentrations associated with low
oxidase activity. Although the enzymatic method is preferred for its biologic relevance,
ceruloplasmin analysis is not a reliable diagnostic parameter for the diagnosis of WD in patients with
liver disease. An important use of the
ceruloplasmin oxidase assay is in the follow-up of patients with WD.
Ceruloplasmin oxidase activity was undetectable in sera from patients with WD who were undergoing long-term
chelation therapy, suggesting an early sign of
copper depletion and a need for subsequent monitoring for symptoms of
copper deficiency.