A family study of the biochemical defects in Wilson's disease.

Estimations of serum copper, serum ceruloplasmin (immunochemical), and urinary amino-acids excretion (quantitative and chromatographic) in 44 healthy relatives of patients with Wilson's disease (39 from one family) are reported. Each technique revealed some abnormal individuals. Good agreement was obtained between the serum copper and serum ceruloplasmin estimations and between the quantitative and chromatographic estimations of amino-acid excretion. Some individuals were abnormal to one or other of the pairs of tests only. These results cast doubt on the hypothesis that the symptoms of Wilson's disease are secondary to a quantitative (or qualitative) abnormality of ceruloplasmin. They also suggest that the mode of inheritance of the biochemical defects may be more complicated than that of a simple recessive mutant gene. Two of the relatives (one pregnant and one immediately post-partum) had a high serum copper level, as is expected in pregnancy, but normal serum ceruloplasmin. This suggests that the mechanism of control of the serum ceruloplasmin concentration may, normally, depend on the serum copper concentration.