Treatment of Wilson's disease with zinc XVI: treatment during the pediatric years.

The objectives were to evaluate appropriate doses of zinc acetate and its efficacy for the maintenance management of Wilson's disease in pediatric cases. Pediatric patients of 1 to 5 years of age were given 25 mg of zinc twice daily; patients of 6 to 15 years of age, if under 125 pounds body weight, were given 25 mg of zinc three times daily; and patients 16 years of age or older were given 50 mg of zinc three times daily. Patients were followed for efficacy (or over-treatment) until their 19th birthday by measuring levels of urine and plasma copper, urine and plasma zinc and through liver function tests and quantitative speech and neurologic scores. Patients were followed for toxicity by measures of blood counts, blood biochemistries, urinalysis, and clinical follow-up. Thirty-four patients, ranging in ages from 3.2 to 17.7 years of age, were included in the study. All doses met efficacy objectives of copper control, zinc levels, neurologic improvement, and maintenance of liver function except for episodes of poor compliance. No instance of over-treatment was encountered. Four patients exhibited mild and transient gastric disturbance from the zinc. Zinc therapy in pediatric patients appears to have a mildly adverse effect on the high-density lipoprotein/total cholesterol ratio, contrary to results of an earlier large study of primarily adults. In conclusion, zinc is effective and safe for the maintenance management of pediatric cases of Wilson's disease. Our data are strongest in children above 10 years of age. More work needs to be done in very young children, and the cholesterol observations need to be studied further.

Treatment of Wilson's disease with zinc. XVII: treatment during pregnancy.

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.

Treatment of Wilson's disease with zinc: XV long-term follow-up studies.

Wilson's disease is an inherited disease of copper accumulation caused by a failure of biliary excretion of excess copper. Accumulated copper causes liver disease in these patients, and in perhaps two thirds of patients, it causes brain damage leading to clinical neurologic or psychiatric dysfunction. Maintenance treatment involves reversing the positive copper balance. The earliest approaches have used chelators, such as penicillamine or trientine, which increase the urinary excretion of copper. A more recent approach has used zinc, which blocks the absorption of copper and increases copper excretion in the stool. Because of the high level of endogenously secreted copper in alimentary secretions, the reabsorption of which is partially blocked by zinc therapy, zinc acts to remove accumulated copper from the body as well as prevent its reaccumulation. In the present article we present data on the long-term follow-up (up to 10 years) of maintenance zinc treatment of 141 patients with Wilson's disease. The data presented document that zinc is effective as a sole therapy in the long-term maintenance treatment of Wilson's disease and that it has a low toxicity. The results demonstrate the efficacy of zinc therapy in treating the presymptomatic patient from the beginning of therapy. We also present limited data on the use of zinc in the treatment of pregnant patients and children who have Wilson's disease; these data also indicate efficacy and low toxicity. The median follow-up period for the group as a whole is 4.8 years; for the presymptomatic patients it is 6.5 years; for the children it is 3.6 years.