Wilson's Disease: Hypothesis of a Deficiency of Copper Excretion Via the Endosome to the Bile

Abstract

To the Editor. —It has been shown that intravenously administered polymeric IgA in the rat is captured by a recepstor in the liver parenchymal cells and transported via the endosomes to the bile canaliculus where it is excreted. 1 We would like to suggest that a similar mechanism could be operating for the transport of a copper-protein to the human bile and that there is a genetic impairment of this pathway in Wilson's disease entailing insufficient copper excretion. As a consequence of the impaired pathway via the endosome, copper would be routed to the lysosome where it accumulates secondarily. The model would explain the insufficient excretion of copper in the bile 2,3 and the lysosomal engorgement in Wilson's disease. The hypothesis of an endosomal route of copper to the bile canaliculus could probably be tested in laboratory animals by the administration of copper and another protein destined for lysosomal breakdown,