Challenges in molecular diagnosis of Wilson disease: viewpoint from the clinical laboratory

Poon, Kok-Siong; Teo, Zhe Hao; Yap, Jun Hean; Koay, Evelyn S C; Tan, Karen

doi:10.1136/jclinpath-2019-206054

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…Its analysis is not included in all studies, which, furthermore, does not always have the same design. The analysis is usually limited to the first 500 bp of the promoter that includes the founder deletion described in Sardinia, c.-441_-427del ( Figure 2 ) [ 76 ]. Nevertheless, mutations placed in more distant regions have been reported as well, suggesting the convenience of a full study of the promoter sequence [ 70 , 77 ].…”

Section: A Mendelian Disease Caused By Mutations In Atp7bmentioning

confidence: 99%

Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

et al. 2021

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Wilson disease (WD) is a rare disorder caused by mutations in ATP7B, which leads to the defective biliary excretion of copper. The subsequent gradual accumulation of copper in different organs produces an extremely variable clinical picture, which comprises hepatic, neurological psychiatric, ophthalmological, and other disturbances. WD has a specific treatment, so that early diagnosis is crucial to avoid disease progression and its devastating consequences. The clinical diagnosis is based on the Leipzig score, which considers clinical, histological, biochemical, and genetic data. However, even patients with an initial WD diagnosis based on a high Leipzig score may harbor other conditions that mimic the WD’s phenotype (Wilson-like). Many patients are diagnosed using current available methods, but others remain in an uncertain area because of bordering ceruloplasmin levels, inconclusive genetic findings and unclear phenotypes. Currently, the available biomarkers for WD are ceruloplasmin and copper in the liver or in 24 h urine, but they are not solid enough. Therefore, the characterization of biomarkers that allow us to anticipate the evolution of the disease and the monitoring of new drugs is essential to improve its diagnosis and prognosis.

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Section: A Mendelian Disease Caused By Mutations In Atp7bmentioning

confidence: 99%

Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

et al. 2021

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“…Liver biopsy for hepatic copper measurement is rarely indicated in Wilson's disease with primarily neurological presentation. On MRI of the brain, the typical “face of giant panda” is found in only 14.3% of the patients; however, tectal plate hyperintensity, central pontine myelinolysis-like abnormalities, and concurrent signal changes in the basal ganglia, thalamus, and brainstem are the more common findings [ 9 - 11 ]. These findings generally regress with successful treatment.…”

Section: Discussionmentioning

confidence: 99%

“Face of a Giant Panda” and “Beating Wings” in a Young Male

Arora¹,

Wasti²,

Suri³

et al. 2022

Cureus

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Mutations in the gene coding for ATPase copper transporting beta polypeptide (ATP7B) cause Wilson's disease, located on chromosome 13. It has mainly hepatic and neurological presentations. Movement disorders are a characteristic finding in Wilson's disease, and "wing-beating tremors" are classical characteristics found on physical examination. We came across and managed a case of Wilson's disease with primarily neurological presentation with classical wing-beating tremors and "face of a giant panda" on radiology. As the patient had very typical findings and he also improved with the treatment, it will be beneficial to the clinicians in their daily practice to identify the disease seeing these clinical findings.

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“…Variant interpretation remains a challenge for clinical laboratories. 26,27 The recommended Leipzig score for diagnosis of WD assigns numerical values to the number of disease-causing mutations to give probable WD diagnoses. The definition of "disease"-causing variant is based on a variety of databases, which can give conflicting answers.…”

Section: Discussionmentioning

confidence: 99%