The Characterisation of Individuals with Respect to Wilson's Disease

Abstract

In the case of heredo-familial diseases it is desirable to identify the abnormal genotype, the homozygously abnormal individual, if possible while still asymptomatic, and the carrier of the abnormal gene or allele, the heterozygote.

So far as Wilson's disease is concerned, it is possible to diagnose individuals as presymptomatic homozygotes by finding Kayser-Fleischer corneal rings on slit-lamp microscopy, or by demonstrating increased liver-copper on needle biopsy.

False-negative results are common, however, and more reliable identification of the presymptomatic homozygote as well as the heterozygote can be achieved by studies of the physiology of copper, using tracer doses of radioactive copper, ⁶⁷copper, which has a physical half life of about 61 hours. Using this method it can be shown:

1. That there is prolonged retention of copper in the whole body in both homozygotes and heterozygotes, the former showing more prolonged retention than the latter.

2. In both there is retention of copper in the liver, again more marked in the homozygote than in the heterozygote.

3. There is decreased intestinal excretion of copper in both cases as manifested by decreased biliary radiocopper and decreased stool radiocopper, and again this is most marked in the homozygote.

4. Urinary excretion of radiocopper is usually increased significantly in the homozygote, but is usually normal or only very slightly increased in the heterozygote.

5. The additional finding of impaired ceruloplasmin biosynthesis is sufficient usually to distinguish with certainty between the presymptomatic homozygote and the heterozygote.