Early and presymptomatic detection of Wilson’s disease at the mandatory 3-year-old medical health care examination in Hokkaido Prefecture with the use of a novel automated urinary ceruloplasmin

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• 作者：Kenji Nakayama ; Mitsuru Kubota ; Yoshinobu Katoh ; Yukiharu Sawada ; Akiko Saito ; Kazuhiko Nishimura ; Eiji Katsura ; Naoshi Ichihara ; Tomohiro Suzuki ; Hirokazu Kouguchi ; Masahide Tamura ; Hiroshi Honma ; Se
• 关键词：Wilson’ ; s disease ; Early detection ; Screening ; Urine ; Ceruloplasmin ; ATP7B ; Genetic analysis ; Molecular diagnosis ; Medical health care examination ; Polaprezinc
• 刊名：Molecular Genetics and Metabolism
• 出版年：2008
• 出版时间：July 2008
• 年：2008
• 卷：94
• 期：3
• 页码：363-367
• 全文大小：230 K

文摘

Wilson’s disease (WND) is an autosomal recessive disorder of copper (Cu) accumulation leading to liver and/or brain damage. Oral chelating agents and diet are effective in treating WND. However, once irreversible damage has occurred, the effect of treatment is diminished and the patient’s quality of life is compromised. For these reasons an effective method for screening has been needed for early detection of presymptomatic patients. We conducted an early and presymptomatic detection of WND using a novel automated assay of ceruloplasmin (Cp) concentration in urine and selected the mandatory medical health care examination for 3-year-old children in Hokkaido Prefecture (the largest administrative division in Japan) as a sampling point. We measured urinary Cp concentrations in 11,362 children using an immunological latex agglutination assay kit developed by us. Among these children we identified a positive case with markedly reduced urinary Cp concentration. Detailed medical examination provided no clinical manifestations to support the diagnosis of WND, although serum Cp and Cu levels were remarkably low in this case. Therefore, we analyzed the WND gene in order to confirm the diagnosis. Sequence analysis revealed that the case was compound heterozygous for the WND gene mutations 2871del.C and D1296N. According to the Ferenci scoring system for WND diagnosis, the case was established as a WND patient at the presymptomatic stage. Consequently, the patient has maintained a good quality of life under medical treatment with polaprezinc administration to date. Our investigation suggests that the screening system for WND using the automated urinary assay at the mandatory medical health care examination for 3-year-old children is a noninvasive and efficient method for the early and presymptomatic diagnosis of WND.