Studies of diagnosis and pathogenesis of Wilson's disease.

We have studied the copper and metallothionein (MT) in culture skin fibroblasts of patients and heterozygotes with Wilson's disease (WD) and controls (5 cases each) after incubation in mediums containing various concentrations of copper (C1: 15.74 mumol/L, C2: 78.70 mumol/L, C3: 157.38 mumol/L, C4: 314.76 mumol/L). The results are as follows: 1. In each of the three groups, the copper/protein ratio (Cu/P) in cytosols of 1-5 passages is significantly higher than that of 6-10, 11-15, 16-20 passages. There are no significant differences among 6-10, 11-15 and 16-20 passages. 2. In standard medium, Cu/P in cytosols of three groups are not significantly different, but Cu/P of patients is significantly higher than that of the other two groups after incubation in C4 medium for 12 or 24 hours. 3. After incubation in C1, C2, C3 and C4 mediums respectively, the Cu/P in cytosols of the three groups only increased in C4 medium with time (within 72 hours). It is higher in the patient group than the other two groups. 4. In the three groups, cytosol copper distributed similarly in two peaks after Sephadex G-75 chromatography, which are on high molecular weight (HMW) proteins and MT fractions respectively. It remained the same after incubation in various concentrations of copper. The copper content found in MT fractions in WD patients is much higher than that of controls and heterozygotes. It is even higher after incubation in various concentrations of copper but no changes was found in controls and heterozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)