Diagnosing Wilson’s Disease under the sword of Damocles

Abstract

Introduction. Antos et al. [7] have reported a case of suspected uniparental disomy leading to an initial erroneous diagnosis of Wilson's Disease on the basis of genetic testing. They discuss the usefulness of the 64 Cu radioactive copper incorporation test as an often-overlooked diagnostic aid. Clinical reflections. Wilson's Disease is difficult to diagnose because of its rarity, diverse clinical presentations, and the absence of a single fail-safe diagnostic test. The identification of mutations in the ATP7B gene has been an invaluable aid in the diagnosis, but genetic testing alone is not infallible, and should not be used as the sole diagnostic test in arriving at a diagnosis of Wilson's Disease. Clinical implications. The diagnosis of Wilson's Disease must be based on a combination of findings that includes clinical history, clinical examination, and diagnostic testing. Genetic testing alone is insufficient.

High value of 64Cu as a tool to evaluate the restoration of physiological copper excretion after gene therapy in Wilson’s disease

“…Similar results were obtained in patients and WD animal models. 21 , 22 , 23 , 25 , 26 , 27 In WT animals, excess of copper is excreted via the biliary and fecal route, while in WD mice, copper is accumulated in the liver and eliminated through the urine; however, this is insufficient to restore an appropriate balance with dietary intake, as toxic copper levels accumulate in tissues, primarily in the liver. VTX-801 administration significantly reduced hepatic copper-64 retention and increased biliary and fecal excretion in a dose-dependent manner at 9 and 18 weeks of age.…”

Neuroimaging in Parkinson’s Disease: necessity or exaggeration?

“…In NPH, early gait problems, with rather wide-base gait (narrow in PD), is present, followed by dementia and urinary incontinence. Wilson's Disease may progress faster, with prominent dystonic postures and hepatic lesions and should be thoroughly diagnosed using a combination of methods, including biochemical (serum ceruloplasmin; serum and urine copper) and ophthalmological (Kayser-Fleisher ring) examinations; genetic testing; and neuroimaging with MRI or transcranial ultrasonography [9][10][11]. Predominant gait problems are also typical for VaP, presenting as so-called lower body parkinsonism (of note: true VaP due to vascular lesions within nigrostriatal pathways is very rare) [9].…”

A study of linear measurement and clinical correlation of brain atrophy in Wilson's disease

“…Therefore, early detection and timely treatment can minimize the impact of brain atrophy on patients and bring the best results (Sastre-Garriga et al, 2020 ). Previous studies have shown that neuroimaging (Shribman et al, 2022 ), sNfL levels (Wang et al, 2022 ), the Unified Wilson's Disease Rating Scale (UWDRS) neurological and psychiatric subscales, and the GAS of the WD Tier 2 score (Volpert et al, 2017 ) can be used as biomarkers of WD (Pfeiffer, 2020 ). Currently, MRI has been reported to be mostly used to diagnose brain atrophy and classify it into diffuse brain atrophy and localized cerebral atrophy based on its scope, degree, and location (Planche et al, 2021 ).…”