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

Nakayama, Kenji; Kubota, Minoru; Katoh, Yoshinobu; Sawada, Yukiharu; Saito, Akiko; Nishimura, Kazuhiko; Katsura, Eiji; Ichihara, Nobutsune; Suzuki, Tomohiro; Kouguchi, Hirokazu; Tamura, Mitsutoshi; Honma, Hiroshi; Kanzaki, Setsuo; Itami, Hitoshi; Ohtake, Akihiko; Kobayashi, Kunihiko; Ariga, Tadashi; Fukui, Kenji; Shimizu, Norikazu; Aoki, Tsugutoshi

doi:10.1016/j.ymgme.2008.03.002

Cited by 28 publications

(21 citation statements)

References 33 publications

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“…Recently, it was reported that the prevalence for Japan, China, and Sardinia (Italy) is higher than the general population [5,6]. The high prevalence (1:10,000) of WND in Japan strongly supports our previous report [7]: one WND patient at the presymptomatic stage was detected through the analyses of 11,362 child subjects using the automated urinary Cp assay at the mandatory medical health care examination for 3-year-old children. Our attempt was to succeed for the first time in early and presymptomatic diagnosis of WND in conjunction with the mandatory medical health care program at the age of 3 years.…”

Section: Introductionsupporting

confidence: 84%

High Expression Of Atp7b MRNA In The Peripheral Blood Mononuclear Cells Of The Long-Evans Cinnamon Rats: An Animal Model Of Wilsons Disease

Nakayama

Katoh²,

Shimizu³

et al. 2013

Hereditary Genet

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The Long-Evans Cinnamon (LEC) rat is an animal model of Wilson's disease. The rat has a mutation in the copper (Cu)-transporting P-type ATPase (Atp7b) gene that is homologous to the human Wilson's disease gene, ATP7B. The LEC rat shows all of the biochemical features of the disease. In this study, we focused on the expression levels of mutant Atp7b mRNAs in the peripheral blood mononuclear cells (PBMCs) of the LEC rats. Using quantitative real-time polymerase chain reaction (quantitative RT-PCR), we analyzed the expression levels of Atp7b mRNAs in the PBMCs cells of both the LEC rats and Long-Evans Agouti (LEA) rats, the latter being utilized as a control for the LEC rat. At the ages of 5 and 8 weeks, the inductions of Atp7b mRNA were manifested in the PBMCs of both male and female LEC rats, while their levels in the livers were significantly lower than those of the LEA rats. These results suggest the diversity of cell-physiological and endocrinological Cu metabolisms between the PBMCs and the livers of the LEC rats. Our findings indicate the possibility of a novel Cu metabolism in the cardiovascular network that is concerned with Atp7b of the PBMCs.

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Section: Introductionsupporting

confidence: 84%

High Expression Of Atp7b MRNA In The Peripheral Blood Mononuclear Cells Of The Long-Evans Cinnamon Rats: An Animal Model Of Wilsons Disease

Nakayama

Katoh²,

Shimizu³

et al. 2013

Hereditary Genet

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“…Holo-ceruloplasmin detections in newborn blood or in urine of 3-6 year-old children have been proposed as potential mass screening strategies [96-98]. To date, however, mass screening has not yet been implemented anywhere.…”

Section: Wilson’s Disease (Wd)mentioning

confidence: 99%

Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment

Kodama

Fujisawa²,

Bhadhprasit³

2012

CDM

155

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Copper is an essential trace element required by all living organisms. Excess amounts of copper, however, results in cellular damage. Disruptions to normal copper homeostasis are hallmarks of three genetic disorders: Menkes disease, occipital horn syndrome, and Wilson’s disease. Menkes disease and occipital horn syndrome are characterized by copper deficiency. Typical features of Menkes disease result from low copper-dependent enzyme activity. Standard treatment involves parenteral administration of copper-histidine. If treatment is initiated before 2 months of age, neurodegeneration can be prevented, while delayed treatment is utterly ineffective. Thus, neonatal mass screening should be implemented. Meanwhile, connective tissue disorders cannot be improved by copper-histidine treatment. Combination therapy with copper-histidine injections and oral administration of disulfiram is being investigated. Occipital horn syndrome characterized by connective tissue abnormalities is the mildest form of Menkes disease. Treatment has not been conducted for this syndrome.Wilson’s disease is characterized by copper toxicity that typically affects the hepatic and nervous systems severely. Various other symptoms are observed as well, yet its early diagnosis is sometimes difficult. Chelating agents and zinc are effective treatments, but are inefficient in most patients with fulminant hepatic failure. In addition, some patients with neurological Wilson’s disease worsen or show poor response to chelating agents. Since early treatment is critical, a screening system for Wilson’s disease should be implemented in infants. Patients with Wilson’s disease may be at risk of developing hepatocellular carcinoma. Understanding the link between Wilson’s disease and hepatocellular carcinoma will be beneficial for disease treatment and prevention.

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“…Although regional clusters of specific mutations have been well described, a customized screening approach taking into account these regional variants may be complicated by ethnically diverse populations and inaccurate information provided with samples. Biochemical results are often imprecise, as elevations in urinary copper excretion tend to occur late in the disease process and fewer than 40% of presymptomatic patients excrete copper less than 100 μg/day (Sternlieb and Scheinberg, 1968; Nakayama et al, 2008). For these reasons, direct sequencing of the ATP7B gene has become the preferred standard and provided the greatest yield in clinical molecular diagnosis.…”

Section: Clinical Molecular Diagnosismentioning

confidence: 99%

The genetics of Wilson disease

Chang

Hahn

2017

Handbook of Clinical Neurology

111

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Wilson disease is an autosomal-recessive disorder of hepatocellular copper deposition caused by pathogenic variants in the copper-transporting gene, ATP7B. Early detection and treatment are critical to prevent lifelong neuropsychiatric, hepatic, and systemic disabilities. Due to the marked heterogeneity in age of onset and clinical presentation, the diagnosis of Wilson disease remains challenging to physicians today. Direct sequencing of the ATP7B gene is the most sensitive and widely used confirmatory testing method, and concurrent biochemical testing improves diagnostic accuracy. More than 600 pathogenic variants in ATP7B have been identified, with single-nucleotide missense and nonsense mutations being the most common, followed by insertions/deletions, and, rarely, splice site mutations. The prevalence of Wilson disease varies by geographic region, with higher frequency of certain mutations occurring in specific ethnic groups. Wilson disease has poor genotype–phenotype correlation, although a few possible modifiers have been proposed. Improving molecular genetic studies continue to advance our understanding of the pathogenesis, diagnosis, and screening for Wilson disease.

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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

Cited by 28 publications

References 33 publications

High Expression Of Atp7b MRNA In The Peripheral Blood Mononuclear Cells Of The Long-Evans Cinnamon Rats: An Animal Model Of Wilsons Disease

High Expression Of Atp7b MRNA In The Peripheral Blood Mononuclear Cells Of The Long-Evans Cinnamon Rats: An Animal Model Of Wilsons Disease

Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment

The genetics of Wilson disease

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