Clinical presentation and mutations in Danish patients with Wilson disease

Møller, Lisbeth Birk; Horn, Nina; Jeppesen, Tina Dysgaard; Vissing, John; Wibrand, Flemming; Jennum, Poul; Ott, Peter

doi:10.1038/ejhg.2011.80

Cited by 44 publications

(28 citation statements)

References 40 publications

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“…Multi exon deletions in ATP7B may be an overlooked cause of WD. In another cohort study, partial deletions of the ATP7B gene were observed in 4% of the alleles (3/70) . Our detection rate (3/88) is similar to the results of this study.…”

Section: Discussionsupporting

confidence: 90%

Presumed missense and synonymous mutations in ATP7B gene cause exon skipping in Wilson disease

Wang

Zhou

Huang

et al. 2018

Liver International

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Our results suggest that aberrant exon skipping associated to putative splicing enhancer disruption and silencer creation is one previously unrecognized mechanism in Wilson disease. What is more, the multiplex ligation-dependent probe amplification assay for the detection of exon deletions may be valuable in individuals with clinical Wilson disease diagnosis where one or no mutation has been identified by sequencing.

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Section: Discussionsupporting

confidence: 90%

Presumed missense and synonymous mutations in ATP7B gene cause exon skipping in Wilson disease

Wang

Zhou

Huang

et al. 2018

Liver International

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“…Detailed information on WD diagnosis and treatment was not provided for this cohort, and other coexistent causes of liver disease were not rigorously excluded, although patients came from diverse locations including Egypt, Greece, Serbia, Italy, and the UK. Furthermore, several other studies describing clinical presentation and outcomes of large cohorts of WD patients from Austria, Czech, Denmark, and Germany mentioned only one or none HCC case(s) during long‐term follow‐up …”

Section: Discussionmentioning

confidence: 99%

No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long‐term follow‐up

Meer

Man

Berg

et al. 2015

J of Gastro and Hepatol

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Background and Aims: Data on risk of hepatocellular carcinoma (HCC) in patients with Wilson disease are scarce. We determine HCC risk in a well-defined cohort of Wilson patients. Methods: All patients with a confirmed diagnosis of Wilson disease (Leipzig score ≥ 4) in three Dutch university referral hospitals were included in this retrospective cohort study. End of follow-up was defined as date of diagnosis of HCC, liver transplantation, death, or last available hospital visit. Also, a meta-analysis was performed to determine incidence and mortality rate of HCC in Wilson disease based on all published cohorts. Results: In total, 130 patients with Wilson disease were followed during a median follow-up of 15 years (range 0.1-51.2). At baseline, cirrhosis was present in 74 patients (57% of total: 64% compensated, and 36% decompensated). At end of follow-up, liver disease severity was improved, stable or deteriorated in 20%, 46%, and 24% of all cases (10% unknown), respectively. Two patients developed HCC (one despite excellent decoppering after 50 years follow-up, the other with newly diagnosed Wilson disease). Estimated annual HCC risk for all patients was 0.09% (95% confidence interval [CI]: 0.01-0.28). Subgroup analysis in cirrhotic patients revealed an annual HCC risk of 0.14% (95% CI: 0.02-0.46). The meta-analysis showed an annual HCC risk of 0.04% (95% CI: 0.01-0.10) and HCC mortality rate of 2.6/10 000 person-years (95% CI: 0.7-7.0). Conclusions: Even in case of cirrhosis, HCC risk is low in Wilson disease. Our data do not support regular HCC surveillance in Wilson disease.

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“…The crude prevalence (or “clinical prevalence”) depends on the disease prevalence but is also affected by the number of overlooked cases (i.e., diagnostic awareness) and the diagnostic delay. Diagnostic delay of up to several years is still a considerable challenge . In this text, the term “crude prevalence” is used pragmatically as the number of reported cases, so it will also be affected by diagnosed but unreported cases.…”

Section: Methodsmentioning

confidence: 99%

The Prevalence of Wilson’s Disease: An Update

et al. 2020

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Background and Aims In 1984, Scheinberg and Sternlieb estimated the prevalence of Wilson’s disease to be 1:30,000 based on the limited available data. This suggested a large number of overlooked cases with potentially fatal consequences. The “Scheinberg‐Sternlieb Estimate” is still widely used, although more recent clinical and genetic studies of higher quality are now available. In the present study, we included these data to update the prevalence estimate. Approach and Results A MEDLINE Ovid, Science Citation Index Expanded, and PubMed systematic search for all relevant studies on the prevalence of Wilson’s disease was conducted. In total, 59 studies (50 clinical and 9 population‐based genetic) were included in the final analysis. We identified 4 recent clinical studies based on nationwide databases of high quality, providing prevalence estimates from 1:29,000 to 1:40,000. Higher frequency populations do exist because of frequent first‐cousin marriages and/or a higher mutation frequency. When calculating prevalence from the incidence related to number of births, estimates were 1:40,000‐1:50,000. Clinical screening studies, including examination for Kayser‐Fleischer rings or ceruloplasmin, did not improve these estimates because of insufficient sample size or selection biases. Population‐based genetic studies in US and UK populations were not in disagreement with the clinically based estimates. At the same time, studies from France and Sardinia suggested that the genetic prevalence may be 3‐4 times higher than the clinical disease prevalence. This raises the question whether the penetrance is indeed 100% as generally assumed. Conclusions The original prevalence estimate from 1984 of 1:30,000‐1:50,000 still appears valid, at least for the United States, Europe, and Asia. In some population‐based studies, the genetic prevalence was 3‐4 times higher than clinically based estimates. The question of penetrance needs further evaluation.

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Clinical presentation and mutations in Danish patients with Wilson disease

Cited by 44 publications

References 40 publications

Presumed missense and synonymous mutations in ATP7B gene cause exon skipping in Wilson disease

Presumed missense and synonymous mutations in ATP7B gene cause exon skipping in Wilson disease

No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long‐term follow‐up

The Prevalence of Wilson’s Disease: An Update

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