Wilson disease is an autosomal recessive disease of a toxic reaction to copper, primarily affecting the brain and liver.^1-5 The disease is due to mutations in the ATP7B gene,^6-8 which produces a protein required for biliary excretion of the body's excess copper.

THE INITIAL TREATMENT of patients with Wilson disease who present with neurologic symptoms is problematic. Of the 3 commercially available anticopper agents, penicillamine often makes about half of these patients irreversibly neurologically worse,¹ trientine hydrochloride is untested but its actions are much like those of penicillamine, and zinc is too slow acting. To fill this therapeutic void, we have been developing ammonium tetrathiomolybdate.^2-4

Therapy of Wilson’s disease continues to evolve. In 1997, zinc acetate was added to the list of drugs approved by the Food and Drug Administration, which includes penicillamine and trientine. The mechanism of zinc’s anticopper action is unique. It induces intestinal cell metallothionein, which binds copper and prevents its transfer into blood. As intestinal cells die and slough, the contained copper is eliminated in the stool. Thus, zinc prevents the intestinal absorption of copper. It is universally agreed that pregnant Wilson’s disease patients should remain on anticopper therapy during pregnancy. There are numerous reports of such patients stopping penicillamine therapy to protect their fetus from teratogenicity, only to undergo serious deterioration and even death from renewed copper toxicity. Penicillamine and trientine have teratogenic effects in animals, and penicillamine has known teratogenic effects in humans. In this report we discuss the results of 26 pregnancies in 19 women who were on zinc therapy throughout their pregnancy. The evidence is good that zinc protects the health of the mother during pregnancy. Fetal outcomes were generally quite good, although one baby had a surgically correctable heart defect and one had microcephaly.(Hepatology 2000;31:364-370.)