A study of the caeruloplasmin concentrations found in 75 patients with Wilson's disease, their kinships and various control groups
Gibbs, K.; Walshe, J.M.
Quarterly Journal of Medicine 48(191): 447-463
1979
ISSN/ISBN: 0033-5622 PMID: 396544 Document Number: 154073
The concentration of blue Cu protein ceruloplasmin in the serum of 195 young, normal adults, 147 patients with neurological diseases and 78 patients with subacute or chronic liver disease was studied. These served as controls for 75 patients with Wilsons disease before treatment was started and during follow up for periods extending up to 20 yr. Members [444] of the Wilson's disease kinships were also studied. Ceruloplasmin was estimated by an enzyme assay using dimethyl p-phenylenediamine as substrate. When necessary, the values were checked by a new immunoenzymatic method and by determining serum Cu. The mean ceruloplasmin concentration in 83 normal males was 333.3 mg/1 (SD = 60.7) In 112 females it was 410.1 mg/1 (SD = 130.2). These 112 females comprised 2 populations: the larger (n = 82) had a mean of 365.6 mg/1 (SD = 92.8) and the smaller (n = 40) a mean of 606.6 mg/1 (SD = 157.5). The former figure was taken as the normal value. The mean value for 75 patients with Wilson's disease was 63.3 mg/1 (SD = 87.6) before treatment; after treatment it fell to 45.0 mg/1 (SD = 79.8). In 11 of these patients the mean ceruloplasmin concentration rose, after treatment, from 108.5 mg/1 (SD = 27.7) to 168.7 mg/1 (SD = 33.6). The mean values for the hepatic and neurological control cases closely approximated to the mean values for sex-matched normals. Both groups showed a wide range of variation with many patients falling outside the normal 95% confidence limits. Low ceruloplasmin values in patients with either hepatic or neurological disease may lead to considerable diagnostic confusion. The mean ceruloplasmin concentration for the obligate heterozygotes was significantly depressed in both males and females but only 36 of 160 fell below the normal 95% confidence limit. The percentage of detectable heterozygotes and the calculated gene frequency fell in more distant relatives. When there was a marked and unexpected discrepancy between the serum ceruloplasmin concentration as estimated by the enzymatic assay and the serum Cu concentration, the ceruloplasmin value was checked by the immunoenzymatic method. In patients with liver disease and in those with treated Wilson's disease the immunoenzymatic was in good aggrement with the serum Cu concentration. In some patients, an inhibitor may be present which interferes with the enzymatic assay. The finding of a low ceruloplasmin level in the serum of patient with undiagnosed hepatic or neurological disease by an enzymatic method cannot be taken as evidence of absence of this protein unless it is confirmed by an immunological technique.