Wilson disease is an inherited disorder of
copper metabolism. Progress has been made in establishing the location of the gene on the long arm of chromosome 13, and in finding nearby probes that can be used to identify affected sibs of newly diagnosed patients. However, the gene has not been cloned, and the molecular nature of the defect remains unknown. The cause of the disease is a failure to excrete unneeded and excessive
copper in the bile for loss in the stool. This may be due to a failure to excrete
copper packaged in
ceruloplasmin into the bile. Clinically, patients usually present during the second to fourth decades of life with liver, neurologic, or
psychiatric disease, but the diagnosis is often missed or delayed. Once a diagnosis of
Wilson disease is considered, reliable studies of
copper variables can be carried out. After diagnosis, patients must receive anticopper treatment for the rest of their lives, to reduce
copper levels and prevent
copper reaccumulation. For life-long maintenance
therapy, we recommend
zinc acetate because of its complete efficacy and lack of toxicity; it acts by blocking
copper absorption. For initial
therapy of the acutely ill patient, no currently available
therapy has proven to be ideal. A
chelator-type
drug, either
penicillamine or
trien, can be used for the initial
therapy of patients who present with
liver disease; transition to
zinc acetate can then be made after a few months. For the initial
therapy of acutely ill patients who present with neurologic disease, chelation should be avoided because neurologic worsening frequently occurs, probably due to redistribution of
copper which temporarily raises the levels of
copper in the brain. For initial treatment,
zinc therapy is also not ideal because it is relatively slow-acting. A new experimental
drug,
tetrathiomolybdate, shows promise in the initial treatment of patients with
Wilson disease. The major challenges ahead include closing the remaining therapeutic hiatuses, cloning and expressing the gene to understand its function, and improving clinical diagnosis so that
therapy can be instituted as quickly as possible.