USE OF A STABLE COPPER ISOTOPE (CU-65) IN THE DIFFERENTIAL-DIAGNOSIS OF WILSONS-DISEASE

1. (CU)-C-65/(CU)-C-63 stable-isotope ratios have been measured in blo od serum after oral administration of the stable isotope (CU)-C-65. Th e incorporation of the isotope into the plasma protein pool was follow ed at various times for up to 3 days, The resulting patterns of enrich ment in healthy control subjects, in Wilson's disease patients and in heterozygotes for the Wilson's disease gene, were similar in appearanc e to those found by others using copper radioactive isotopes, After an initially high enrichment at 2 h after dosage, the Wilson's disease c ases, in contrast to the control subjects, did not show a secondary ri se in isotope enrichment of the plasma pool after 72 h, demonstrating a failure to incorporate copper into caeruloplasmin. The Wilson's dise ase heterozygotes had variable degrees of impairment of isotope incorp oration, not always distinguished from those of control subjects. 2. T he stability of the isotope also permits the copper tracer to be follo wed for a longer period, Ten healthy subjects were studied for over 40 days, allowing the biological half-time of an oral dose of copper to be determined (median 18.5 days, 95% confidence interval 14-26 days), Known heterozygotes for the Wilson's disease gene were found to have a significantly increased biological half-time for removal of copper fr om the plasma pool (median 43 days, 95% confidence interval 32-77 days ). 3. The incorporation of (CU)-C-65 in patients with diseases of the liver (other than Wilson's disease) was found to be similar to that in control subjects, aiding differential diagnosis.