The Urinary Excretion of Radiocopper in Presymptomatic and Symptomatic Wilson's Disease, Heterozygotes and Controls: Its Significance in Diagnosis and Management

Abstract

Radiocopper (64Cu, 67CU), given intravenously, has been used to study the pattern of excretion of copper in patients with presymptomatic, symptomatic and treated Wilson's disease, together with heterozygotes for the Wilson's disease gene and a control group of patients with a variety of neurological lesions mimicking Wilson's disease. Urine was collected for three periods after injection, 0 to 8 hours, 8 to 24 hours, at which time a test dose of penicillamine was given, and from 24 to 30 hours. Stable (endogenous) copper was also estimated on these samples and specific activity was determined. This was multiplied by a correction factor to allow for variations in dose and body weight. The findings for stable copper in urine were largely predictable. Controls and heterozygotes had the least copper excretion, the amounts rising in the presymptomatic to a peak in the symptomatic patients. Institution of therapy was associated with a fall in copper excretion pro rata with time. The most important radiochemical findings were as follows. Heterozygotes excreted less of the injected copper than controls both under basal conditions and after penicillamine. Presymptomatic patients excreted less radiocopper than heterozygotes after penicillamine although the excretion during the basal 24 hour period was very much greater. Patients with symptomatic Wilson's disease had by far the highest excretion of radiocopper in all three time periods which fell after treatment, pro rata with time, as had been found for stable copper. These results were subjected to computer analysis. There was no overlap between the various groups with the exception of a single control subject who had combined pyramidal and extrapyramidal system degeneration of obscure aetiology. This patient was classified by the computer study as 'heterozygote'. These findings lend further support to the hypothesis that the loss of a single gene for copper balance can be detected with a high degree of accuracy and also that presymptomatic patients can be selected from a sibship for prophylactic treatment without the risk of subjecting healthy heterozygotes to unnecessary and potentially hazardous long-term therapy.