Observations on ceruloplasmin in Wilson's disease.

In the light of present knowledge hepatolenticular degeneration is classified as a metabolic disease, probably based on an inborn error of metabolism and transmitted by an autosomal recessive gene. The biochemical manifestations of Wilson's disease have been studied extensively and were summarized in several recent reviews (1-4). The findings point to aberrations in copper and protein metabolism, but the nature of the basic metabolic defect and the mechanism of the disease are still in the realm of speculation. The most consistent biochemical abnormality in Wilson's disease is the deficiency of the copper containing a2 globulin, ceruloplasmin. It was suggested that a defect in the production of this protein may be the basic metabolic abnormality, and Wilson's disease has been classed accordingly as one of the pathological conditions resulting from the congenital deficiency of a specific plasma protein (5, 6). This paper describes, for the first time as far as we are aware, two patients with Wilson's disease and normal serum concentration of ceruloplasmin. These two patients were investigated in detail, including studies with radioactive copper, in order to substantiate their diagnosis and also in the hope that the results might contribute to our knowledge of the basic mechanism of Wilson's disease. For the purpose of comparison a third patient who exhibited all the typical clinical and biochemical characteristics of Wilson's disease was also studied by the same methods.