Western blot analysis in patients with hypocaeruloplasminaemia.
Inherited copper toxic disease, Wilson's disease, is an autosomal recessive disorder arising from a defect in biliary copper excretion. Although there are several pathognomonic clinical features, such a multisystem disease can be difficult to diagnose, particularly in the early stages of copper toxicity. Even measurements of serum copper and caeruloplasmin, the major copper-transporting protein typically reduced in Wilson's disease, may mimic other metabolic conditions such as Menke's disease and chronic active hepatitis. We have previously shown that the major biliary isoform of copper-transporting protein is 125 kDa caeruloplasmin, and this is always absent in the bile of Wilson's disease patients. In this paper we describe Western blot analysis of molecular species of caeruloplasmin in hypocaeruloplasminaemia, which can distinguish between the overlap which occurs in Wilson's disease homozygotes, heterozygotes and other conditions mimicking Wilson's disease. This may be useful for identifying patients with low plasma caeruloplasmin concentrations, and hepatic or neurological clinical features which may also be found in Wilson's disease.