Keisuke Eda1, Tatsuki Mizuochi1, Itaru Iwama2, Ayano Inui3, Yuri Etani4, Mariko Araki5, Shinya Hara6, Hideki Kumagai7, Shin-Ichiro Hagiwara8, Kei Murayama9, Jun Murakami10, Norikazu Shimizu11, Hiroko Kodama12, Ryosuke Yasuda1, Yugo Takaki1, Yushiro Yamashita1. 1. Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. 2. Department of Pediatrics, Okinawa Chubu Hospital, Uruma, Japan. 3. Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan. 4. Department of Pediatric Gastroenterology, Nutrition, and Endocrinology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. 5. Department of Pediatrics, Kochi Medical School, Kochi University, Nankoku, Japan. 6. Department of Pediatrics, Toyota Memorial Hospital, Toyota, Japan. 7. Department of Pediatrics, Jichi Medical University, Shimotsuke, Japan. 8. Division of General Pediatrics, Saitama Children's Medical Center, Saitama, Japan. 9. Department of Metabolism, Chiba Children's Hospital, Chiba, Japan. 10. Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Yonago, Japan. 11. Department of Pediatrics, Toho University School of Medicine, Ohashi Medical Center, Tokyo, Japan. 12. Department of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan.
Abstract
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.
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.
Authors: Abolfazl Avan; Anna Członkowska; Susan Gaskin; Alberto Granzotto; Stefano L Sensi; Tjaard U Hoogenraad Journal: Int J Mol Sci Date: 2022-08-18 Impact factor: 6.208