Use of the stable isotope 65Cu test for the screening of Wilson's disease in a family with two affected members.

BACKGROUND/AIMS: An improved method for the study of copper metabolism in Wilson's disease, using a stable, rather than radioactive, copper isotope (65Cu) has recently been described. We report on the use of this method for the study of a family with two members affected by Wilson's disease.

SUBJECTS: The family comprised parents and four siblings: one 20-year-old male and three females, aged 22, 17 and 5 years, respectively. The boy and the 17-year-old girl both presented with liver cirrhosis. Diagnosis of Wilson's disease was suggested by elevated liver copper content and/or low caeruloplasmin levels and Kayser-Fleischer ring.

METHODS: All family members were given an oral dose of 3 mg of 65Cu. Blood samples were taken at 0, 1, 2, 6, 24, 48, and 72 hours. In 4 subjects, additional blood samples were drawn at 7, 14 and 21 days after dosage. The ratio 65Cu:63Cu in serum was determined in all samples by means of Inductively Coupled Plasma Mass Spectrometry.

RESULTS: The diagnosis of Wilson's disease was confirmed in the two symptomatic members by the unequivocal decrease observed in the 65Cu percent enrichment, which approached zero by 72 hours. In contrast, Wilson's disease could be definitely excluded in both siblings, one of whom only 5 years old, on the evidence of net secondary peaks, showing normal incorporation of 65Cu into caeruloplasmin. These findings were later confirmed by genetic analysis. Parents, who carried defective genes with different mutations, also showed different abnormalities of copper metabolism.

CONCLUSIONS: The oral test with the stable copper isotope 65Cu is a safe, non invasive option able to exclude Wilson's disease in patients with a difficult diagnosis or in a presymptomatic stage. However, positive tests must still be confirmed by copper dosage in liver biopsies, as heterozygotes can present with severe alterations of copper metabolism, without developing symptoms of the disease. The use of this test in conjunction with genetic analysis on a larger number of heterozygous subjects may add to the understanding of the Wilson's disease defect.