Mass screening for Wilson's disease: Results and recommendations

Abstract

Wilson's disease is a treatable inherited disorder of copper metabolism. Established treatments include the use of oral chelating agents and the establishment of a minimum copper diet, although prognosis mainly depends on the extent of liver or nervous system damage present before treatment. Once irreversible damage has occurred, the effect of these treatments is diminished and the patient's quality of life compromised. Therefore, the establishment of a mass screening system able to detect Wilson's disease patients presymptomatically has been discussed. Recently, a monoclonal antibody specific to holoceruloplasmin has been developed. This antibody was used in a nationwide screening trial of 126,810 newborn infants, but no Wilson's disease patients were identified. However, three patients out of 24,165 were diagnosed with Wilson's disease using this specific antibody in a screening performed during the period from late infancy to elementary school. The age of 3 years is thought to be the best point for Wilson's disease mass screening. In this paper, a review of mass screening for Wilson's disease in Japan using a specific monoclonal antibody to holoceruloplasmin is presented.

Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity

“…The prevalence of WD in Hong Kong Han Chinese was 1 in 5,400. Our findings concurred with the prevalence reported in other East-Asian countries (Kim et al 1998;Ohura et al 1999;Yamaguchi et al 1999) that WD seems more prevalent in East Asia than in western countries. Intriguingly, p.R778L has been reported only in EastAsian populations and is absent in other ethnic groups.…”

Diagnostic Accuracy of Serum Ceruloplasmin in Wilson Disease: Determination of Sensitivity and Specificity by ROC Curve Analysis among ATP7B-Genotyped Subjects

“…The disease frequency is highly variable, and WD is seen more frequently in Sardinia, China, Japan, and other Asian populations (2)(3)(4)(5)(6)(7)(8)(9). Underdiagnosis of WD is highly likely, especially during the asymptomatic phase and in patients with atypical presentations.…”

Tryptic Peptide Analysis of Ceruloplasmin in Dried Blood Spots Using Liquid Chromatography–Tandem Mass Spectrometry: Application to Newborn Screening

“…In 1 study, the mean (SD) CP concentrations in the DBS of healthy individuals, WD carriers, and WD patients were as 30.5 (9.5) (7 ). It has been shown, however, that the ceruloplasmin concentration is physiologically low in newborns (10 ), prompting the question whether screening for WD in the newborn period would be possible. Kroll et al (11 ) answered this question with a retrospective study showing that WD patients had much lower CP concentrations in their original newborn blood spots than age-matched controls.…”

“…Several pilot studies have been conducted measuring CP in the dried blood spots (DBS) of children using ELISAs to identify the patients with presymptomatic WD (7)(8)(9)(10). In 1 study, the mean (SD) CP concentrations in the DBS of healthy individuals, WD carriers, and WD patients were as 30.5 (9.5) (7 ).…”