A Study of the Caeruloplasmin Concentrations found in 75 Patients with Wilson's disease, their Kinships and Various Control Groups

Abstract

We have studied the concentration of the blue copper protein caeruloplasmin in the serum of 195 young, normal adults, 147 patients with neurological diseases and 78 patients with subacute or chronic liver disease. These have served as controls for 75 patients with Wilson's disease before treatment was started and during follow up for periods extending up to 20 years. We have also studied 444 members of the kinships. Caeruloplasmin has been estimated by an enzyme assay using dimethyl pphenylenediamine as substrate and, when necessary, we have checked the values so obtained by a new immunoenzymatic method and also by determining serum copper. The mean caeruloplasmin concentration in 83 normal males was 333.3 mg/l (S.D. 60·7). In 112 females it was 410·1 mg/l (S.D. 130·2). These 112 females were shown to comprise two populations, the larger ( n 82) had a mean of 365·6 mg/l (S.D. 92·8) and the smaller a mean of 606·6 mg/l (S.D. 157·5). The former figure is taken as the normal. The mean value for 75 patients with Wilson's disease was 63·3 mg/l (S.D. 87·6) before treatment; after treatment it fell to 45·0 mg/l (S.D. 79·8). However in 11 of these patients the mean caeruloplasmin concentration rose, after treatment, from 108·5 mg/l (S.D. 27·7) to 168·7 mg/l (S.D. 33·6). The mean values for the hepatic and neurological control cases closely approximated to the mean values for the sex matched normals. However both these groups showed a wide range of variation with many patients falling outside the normal 95 per cent confidence limits. Low caeruloplasmin values in patients with either hepatic or neurological disease may lead to considerable diagnostic confusion. The mean caeruloplasmin concentration for the obligate heterozygotes was significantly depressed in bath males and females but only 36 out of 160 fell below the normal 95 per cent confidence limit. The percentage of detectable heterozygotes fell, as did the calculated gene frequency, in more distant relatives. When there was a marked and unexpected discrepancy between the serum caeruloplasmin concentration as estimated by the enzymatic assay and the serum copper concentration the caeruloplasmin value was checked by the immunoenzymatic method. In patients with liver disease and in those with treated Wilson's disease the immunoenzymatic method was found to be in good agreement with the serum copper concentration. This suggests that there is, in some patients, an inhibitor present which interferes with the enzymatic assay. The finding of a low caeruloplasmin level in the serum of a 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.