Zinc monotherapy for young children with presymptomatic Wilson disease: A multicenter study in Japan.

Abstract

Few studies of zinc monotherapy for presymptomatic Wilson disease have focused on young children. We therefore evaluated long-term efficacy and safety of zinc monotherapy for such children and established benchmarks for maintenance therapy. We retrospectively and prospectively examined children under 10years old with presymptomatic Wilson disease who received zinc monotherapy from time of diagnosis at 12 participating pediatric centers in Japan. Twenty-four patients met entry criteria. Aspartate aminotransferase and alanine aminotransferase decreased significantly beginning 1month after initiation of treatment and usually remained under 50U/L from 1 to 8years of treatment. Twenty four-hour urinary copper decreased significantly at 6months and usually remained under 75μg/day and between 1 and 3μg/kg/day for the remainder of the study. All patients continued to take zinc, and none became symptomatic. In patients under 6years old who received 50mg/day of zinc as an initial dose, aspartate aminotransferase and alanine aminotransferase significantly decreased at 1month after initiation of treatment, as did γ-glutamyltransferase and 24-h urinary copper at 6months. To our knowledge, this is the first multicenter study of zinc monotherapy for young children with presymptomatic Wilson disease. Such monotherapy proved highly effective and safe. Maintaining normal transaminase values (or values under 50U/L when normalization is difficult) and 24-h urinary copper excretion between 1 and 3μg/kg/day and under 75μg/day is a reasonable goal. An initial dose of 50mg/day is appropriate for patients under 6years old.