Pilot study of screening for Wilson disease using dried blood spots obtained from children seen at outpatient clinics

Ohura, Toshihiro; Abukawa, Daiki; Shiraishi, H.; Yamaguchi, Akihiro; Arashima, Shinichiro; Hiyamuta, Shuichi; Tada, Keiya; Iinuma, Kazuie

doi:10.1023/a:1005455401076

Cited by 40 publications

(18 citation statements)

References 10 publications

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“…Infants with the ATP7B classical form cited from the international literature. [11][12][13][14][15][16] Kainan Hospital, and Saiseikai Yokohama Toub Hospital). Serum levels of ALT were determined by one point at entry in all patients with WD, except for those with Coombs-negative hemolytic anemia and complicated acute diseases.…”

Section: Methodsmentioning

confidence: 99%

“…Forty-five Japanese patients were selected from the databases of three institutes (Aichi Gakuin University School of Pharmacy, Kainan Hospital, and Saiseikai Yokohama Toub Hospital), and 7 infant patients were cited based on a literature review of PubMed to identify relevant papers written in English since 1993. [11][12][13][14][15][16] Clinical data of two Japanese patients were analyzed twice because they were followed for years without anti-copper regimens.…”

Section: Patientsmentioning

confidence: 99%

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Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Hayashi

Watanabe

Inui³

et al. 2019

Journal of Clinical and Translational Hepatology

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Background and Aims: The liver is the first organ affected by toxic copper in the classical and severe hepatic forms of Wilson's disease (WD). Because their associated chronic liver damage is mostly asymptomatic, an intervention using a special test including serum alanine aminotransferase (ALT) activity is needed for detecting WD. Methods: Using the modified international criteria for the diagnosis of WD, 45 patients were selected from the collective databases of our institutions, and 7 infants were reviewed from the literature. Two patients had the severe hepatic form, with normoceruloplasminemia and no mutations in ATP7B. The rapid ALT change during hemolytic anemia was adjusted for a baseline. The diagnostic potential of the ALT test was assessed from the age-dependent natural course of the liver damage of WD. Results: The natural course had three stages. ALTs were still low in some infants younger than 4 years-old. They were high in all children between the ages of 4 and 8 years-old; then, they reduced to low levels in some patients over 9 years of age. The high ALT stage represents chronic active hepatitis, and the subsequent low ALT stage is due to silent cirrhosis. The hepatic copper content is a reliable but invasive test, while urinary copper secretion is an alternative, non-invasive test for copper toxicosis of WD. The serum ceruloplasmin and ATP7B analyses are subtype tests of WD. The response to anti-copper regimens is the final test result. Conclusions: ALT could be the first parameter to test to detect WD in children between the ages of 4 and 8 years.

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Section: Methodsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Hayashi

Watanabe

Inui³

et al. 2019

Journal of Clinical and Translational Hepatology

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“…21 More recent mass screening studies undertaken in East Asia suggested a considerably higher prevalence of WD (1:1,500 – 1:3,000) based on ceruloplasmin (CP) level measurements in large cohorts. 22, 23 We have recently completed the first genetic prevalence study of WD in the UK. The entire ATP7B coding region and adjacent splice sites were sequenced in 1,000 apparently healthy neonatal controls.…”

Section: Prevalencementioning

confidence: 99%

Wilson's disease and other neurological copper disorders

Bandmann

Weiss

Kaler

2015

The Lancet Neurology

786

534

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Summary The classic copper metabolism disorder, Wilson disease (WD), was first defined in 1912. Both early onset presentations in infancy and late onset manifestations in adults > 70 years are now well recognized. Modern biochemical and genetic prevalence studies suggest that WD may be considerably more common than previously appreciated. Early diagnosis of WD is crucial to ensure that patients can be started on adequate treatment but uncertainty remains about the best possible choice of medication. Direct genetic testing for ATP7B mutations is increasingly available to confirm the clinical diagnosis of WD. WD needs to be differentiated from other conditions that present clinically with hepatolenticular degeneration or share biochemical abnormalities with WD, such as reduced serum cerulo plasmin levels. Disordered copper metabolism is also implied in an increasing number of other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations, and the common late-onset neurodegenerative disorders Alzheimer’s disease and Parkinson’s disease.

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“…WD has been found worldwide, with an estimated prevalence of one case per 30,000 live births in most populations [ 3 ]. The prevalences of WD are various, showing higher prevalences in Sardinia, China, Japan, and other Asian populations [ 4 5 6 ]. The prevalence of pediatric WD was recently reported to be one in 37,000 children in Korea [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of Ceruloplasmin in the Diagnosis of Pediatric Wilson's Disease

Kim

Cho

et al. 2015

Pediatr Gastroenterol Hepatol Nutr

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PurposeMeasurement of serum ceruloplasmin level is the first step in screening for Wilson's disease (WD). Despite the rarity of WD in the general population, ceruloplasmin levels are routinely measured through hepatitis screening in both adults and children. Herein, we evaluated the diagnostic value of ceruloplasmin for the diagnosis of WD among children with hepatitis.MethodsWe retrospectively reviewed data on serum ceruloplasmin levels measured as a serologic marker for patients with hepatitis at Asan Medical Center (Seoul, Korea) between from January 2004 to November 2013. The diagnosis of WD was confirmed by the identification of pathogenic variants in the ATP7B gene. To determine the diagnostic accuracy of ceruloplasmin, receiver operation characteristic (ROC) curves were constructed and the area under curve (AUC) were calculated.ResultsMeasurements of serum ceruloplasmin were performed in 2,834 children who had hepatitis. Among these, 181 (6.4%) children were diagnosed with WD. The sensitivity, specificity, and accuracy of a ceruloplasmin level of <20 mg/dL in the discrimination of WD were 93.4%, 84.2%, and 84.8%, respectively. In this study, 418 (14.7%) false-positive cases and 12 (0.4%) false-negative cases were noted. Using a ROC curve, a ceruloplasmin level of ≤16.6 mg/dL showed the highest AUC value (0.956) with a sensitivity of 91.2%, a specificity of 94.9%, and an accuracy of 94.7%.ConclusionThe measurement of serum ceruloplasmin was frequently used for the screening of WD in children, despite a low positive rate. The diagnostic value of ceruloplasmin may be strengthened by adopting a new lower cut-off level.

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Pilot study of screening for Wilson disease using dried blood spots obtained from children seen at outpatient clinics

Cited by 40 publications

References 10 publications

Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Wilson's disease and other neurological copper disorders

Diagnostic Value of Ceruloplasmin in the Diagnosis of Pediatric Wilson's Disease

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