title: 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 assay.
abstract: 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.
authors.affiliation: Hokkaido Institute of Public Health, North 19 West 12, Kita-ku, Sapporo 060-0819, Hokkaido, Japan. ken_naka@iph.pref.hokkaido.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakayama
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kubota
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Katoh
authors.forename: Yukiharu
authors.initials: Y
authors.lastname: Sawada
authors.forename: Akiko
authors.initials: A
authors.lastname: Saito
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishimura
authors.forename: Eiji
authors.initials: E
authors.lastname: Katsura
authors.forename: Naoshi
authors.initials: N
authors.lastname: Ichihara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kouguchi
authors.forename: Masahide
authors.initials: M
authors.lastname: Tamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Honma
authors.forename: Setsuo
authors.initials: S
authors.lastname: Kanzaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Itami
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ohtake
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
authors.forename: Norikazu
authors.initials: N
authors.lastname: Shimizu
authors.forename: Tsugutoshi
authors.initials: T
authors.lastname: Aoki
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000465:Algorithms; D001331:Automation; D027682:Cation Transport Proteins / Q000235:genetics; D002570:Ceruloplasmin / Q000032:analysis* / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D003938:Diagnostic Techniques, Digestive System / Q000295:instrumentation; D042241:Early Diagnosis; D005260:Female; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D006801:Humans; D007564:Japan; D008297:Male; D018580:Mandatory Testing / Q000379:methods*; D010375:Pedigree
chemical_list: D027682:Cation Transport Proteins; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases