Zinc monotherapy for young children with presymptomatic Wilson disease: A multicenter study in Japan
Keisuke Eda1, Tatsuki Mizuochi1, Itaru Iwama2
1Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.
Insights
Zinc monotherapy is effective and safe for young children with presymptomatic Wilson disease. This treatment helps maintain normal liver enzymes and copper levels, preventing symptom development.
Area of Science:
- Pediatric Hepatology
- Wilson Disease Research
- Mineral Metabolism
Background:
- Limited data exists on zinc monotherapy for presymptomatic Wilson disease in young children.
- Establishing long-term efficacy and safety benchmarks is crucial for this population.
Purpose of the Study:
- To evaluate the long-term efficacy and safety of zinc monotherapy in children under 10 with presymptomatic Wilson disease.
- To establish maintenance therapy benchmarks for this demographic.
Main Methods:
- Retrospective and prospective study of 24 children under 10 years old with presymptomatic Wilson disease.
- Zinc monotherapy administered from diagnosis across 12 Japanese pediatric centers.
Main Results:
- Significant decrease in AST and ALT within 1 month, typically <50 U/L for 1-8 years.
- Significant decrease in 24-hour urinary copper by 6 months, typically <75 μg/day and 1-3 μg/kg/day.
- All patients tolerated zinc, remained asymptomatic; initial 50 mg/day dose effective for those <6 years.
Conclusions:
- Zinc monotherapy is highly effective and safe for young children with presymptomatic Wilson disease.
- Targeting normal transaminases (<50 U/L if needed) and urinary copper (1-3 μg/kg/day, <75 μg/day) are reasonable goals.
- An initial dose of 50 mg/day is appropriate for children under 6 years old.
Background And Aim:
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.
Methods:
We retrospectively and prospectively examined children under 10 years old with presymptomatic Wilson disease who received zinc monotherapy from time of diagnosis at 12 participating pediatric centers in Japan.
Results:
Twenty-four patients met entry criteria. Aspartate aminotransferase and alanine aminotransferase decreased significantly beginning 1 month after initiation of treatment and usually remained under 50 U/L from 1 to 8 years of treatment. Twenty four-hour urinary copper decreased significantly at 6 months and usually remained under 75 μg/day and between 1 and 3 μg/kg/day for the remainder of the study. All patients continued to take zinc, and none became symptomatic. In patients under 6 years old who received 50 mg/day of zinc as an initial dose, aspartate aminotransferase and alanine aminotransferase significantly decreased at 1 month after initiation of treatment, as did γ-glutamyltransferase and 24-h urinary copper at 6 months.
Conclusions:
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 50 U/L when normalization is difficult) and 24-h urinary copper excretion between 1 and 3 μg/kg/day and under 75 μg/day is a reasonable goal. An initial dose of 50 mg/day is appropriate for patients under 6 years old.
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