Treatment of Wilson's disease with penicillamine and zinc salts: a follow-up study

Abstract

Wilson's disease (WD) is an autosomal recessive disorder characterized by excessive accumulation of copper in the liver and later in the brain and other organs. Penicillamine acts as a reductive chelator. Zinc salts induce the synthesis of metallothionein in cells. Thus these two drugs are theoretically synergistic for the treatment of the disease. However, the two drugs may also have some unfavorable interactions. In this study, the effect of the therapy with combined penicillamine and zinc salts was evaluated based on the follow-up observations of 21 patients with Wilson's disease. Using the combined therapy of penicillamine [10-30 mg/(kg.d)] and zinc (22.5 mg, 3 times per day), follow-up study by hospitalization or communication with telephone or mail. Before treatment, all the 21 patients were suffered from chronic liver disorder. Among them, 13 patients (62%) showed to be reactive to the treatment for their liver disorder, 5 patients (24%) died, and 3 patients (14%) dropped off our follow-up study. Among the 5 patients who died, 3 died within 40 days after treatment, one had taken penicillamine only 8 mg/(kg.d), and one died after discontinuation of the treatment by the parents. Of the 12 patients having neurological involvement, neurological symptoms disappeared or markedly improved in 11 patients after treatment. One patient dropped off the follow-up study. The patient with renal tubular acidosis responded well to the treatment. Urine routine analysis was followed up in 6 of the 7 patients with hematuria. Hematuria disappeared in one, became less severe in 1, and remained unchanged in 4 patients. Hypersensitivity to penicillamine was found in one patient. WBC and platelet were found decreased further in 3 patients after the medications. The combined therapy with penicillamine and zinc salts was effective in treatment of patients with Wilson's disease.