Pathogenesis of Wilson disease

Scheiber, Ivo F.; Brůha, Radan; Dušek, Petr

doi:10.1016/b978-0-444-63625-6.00005-7

Cited by 77 publications

(77 citation statements)

References 159 publications

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“…The effect of copper toxicity on the neurologic system can be understood based on Wilson's disease. Notably, excessive copper deposition within neurons disturbed cortical function and exacerbated dementia and excessive cerebral copper dysregulated dopaminergic neurons by influencing the MAT metabolism [38]. As per our results, the sensitivity and specificity of the total TRODAT ratio for predicting RLS in the control and ESRD with RLS groups were 100.0% and 91.8%, respectively, at a cutoff value of 2.50 (AUC was 0.955, p = 0.021, not demonstrated).…”

Section: Discussionsupporting

confidence: 57%

Tc-99m TRODAT-1 SPECT is a Potential Biomarker for Restless Leg Syndrome in Patients with End-Stage Renal Disease

Hou

Fan

Huang

et al. 2020

JCM

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Rationales: Restless leg syndrome (RLS) is a common complication in patients with end-stage renal disease (ESRD). However, there is a lack of biomarkers linking uremic RLS to dopaminergic neurons. Previous studies demonstrated that Tc-99m TRODAT-1 SPECT was a biomarker for RLS but the correlation between the physiologic parameter was lacking. Methods: Overall, 32 patients were enrolled in the study and divided into the following 3 groups: (1) control (n = 13), (2) ESRD without RLS (n = 8) and (3) ESRD with RLS (n = 11). All patients had a clinical diagnosis of RLS and received Tc-99m TRODAT-1 SPECT. A subgroup analysis was performed to compare differences between the control and ESRD with RLS groups. Tc-99m TRODAT-1 SPECT was performed and activities in the striatum and occipital areas were measured using manually delineated regions of interest (ROIs) by an experienced nuclear medicine radiologist who was blinded to clinical data. Results: The total ratio of Tc-99m TRODAT SPECT was lower in the ESRD with RLS group (p = 0.046). The uptake ratio of TRODAT negatively correlated with serum parathyroid hormone (r = −0.577, p = 0.015) and ferritin (r = −0.464, p = 0.039) concentrations. However, the uptake positively correlated with the hemoglobin concentration (r = 0.531, p = 0.011). The sensitivity and specificity of the total TRODAT ratio for predicting RLS in the overall population were 95.0% and 67.7%, respectively, at a cutoff value of 0.980 (area under the curve of receiver operating characteristic curve was 0.767, p = 0.024). Conclusion: In patients with ESRD and RLS, Tc-99m TRODAT might be a potential biomarker. Dysregulated hemoglobin, serum parathyroid hormone and serum ferritin concentrations might influence the uptake of the TRODAT ratio.

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Section: Discussionsupporting

confidence: 57%

Tc-99m TRODAT-1 SPECT is a Potential Biomarker for Restless Leg Syndrome in Patients with End-Stage Renal Disease

Hou

Fan

Huang

et al. 2020

JCM

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“…At the time of LT, 5 (20%) patients were not receiving medical treatment, whereas 13 (52%) and 5 (20%) were taking D-penicillamine and zinc sulfate monotherapy, respectively. The median WD prognostic index, (26) Child-Pugh, and MELD scores were 10 (3-14), 11 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), and 27 (6-49), respectively. More than 80% of patients were hospitalized at the time of their LT, necessitating admission to the intensive care unit (ICU) due to multiorgan failure in 6 patients.…”

Section: Characteristics Of Wd Patients At the Time Of Ltmentioning

confidence: 98%

“…Hepatic involvement can range from an asymptomatic increase in serum transaminases to acute liver failure (ALF), compensated cirrhosis, acute‐on‐chronic liver failure (ACLF), and end‐stage liver disease (ESLD). The protean severity of neurological abnormalities, including Parkinson’s‐like symptoms, tremor, ataxia, and dystonia, is often not associated with the severity of liver involvement …”

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confidence: 99%

“…including Parkinson's-like symptoms, tremor, ataxia, and dystonia, is often not associated with the severity of liver involvement. (2)(3)(4)(5) Since 1971, liver transplantation (LT) has represented an effective treatment for WD patients with liver involvement because it removes the biochemical deficit and improves quality of life. (6)(7)(8) The absence of postoperative disease recurrence and the young age at LT explain the excellent postoperative survival curves (1-year graft and patient survival rates of 73%-86% and 79%-91%, respectively, depending also on the type of transplantation and the disease phenotype).…”

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confidence: 99%

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Outcomes of Liver Transplant for Adults With Wilson’s Disease

et al. 2020

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Wilson’s disease (WD) is a rare genetic disorder with protean manifestations. Even if liver transplantation (LT) could represent an effective therapeutic option for patients with end‐stage liver disease, it has remained controversial in the presence of neuropsychiatric involvement. This study aimed to examine the frequency of adult LT for WD in Italy, focusing on the disease phenotype at the time of LT. A retrospective, observational, multicenter study was conducted across Italy exploring the frequency and characteristics of adults transplanted for WD between 2006 and 2016. A total of 29 adult WD patients underwent LT during the study period at 11 Italian LT centers (accounting for 0.4% of all LTs performed), and 27 of them were considered in this analysis (male/female, n = 9/18; age at LT, 29 years [19‐60 years]; median Model for End‐Stage Liver Disease score at LT, 27 [6‐49]). Isolated hepatic phenotype was the indication for LT in 17 (63%) patients, whereas 2 (7%) patients underwent LT for neurological impairment on compensated liver disease. Overall 1‐ and 5‐year patient survival was excellent (88% and 83%, respectively). Neuropsychiatric symptoms early after LT completely recovered in only a few patients. In conclusion, WD remains an uncommon, unusual indication for LT in Italy, displaying good post‐LT graft and patient survival. Because isolated neuropsychiatric involvement represents a rare indication to LT, more data are needed to properly assess the value of LT for WD in this subset of patients.

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“…The mechanism of Wilson's disease with massive cerebral infarction is not clear, and may be related to the following reasons: When the accumulation of Cu in the body exceeds the load capacity of various organelles containing copper protein in the tissues, unbound or loosely bound copper can induce oxidative stress and/or exert its toxicity through directly inhibited protein function 6 . The production of reactive oxygen species (Ros) far outpaces the removal of intracellular antioxidant defenses, the accumulation of free radicals leads to oxidative stress, which leads to damage or even apoptosis of brain cells, in turn leads to neurologic de cits.…”

Section: Discussionmentioning

confidence: 99%

Wilson's Disease Complicated with Massive Cerebral Infarction：A Case Report

Zhang

Chen

et al. 2020

Preprint

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Abstract Hepatolenticular degeneration, also known as Wilson's disease, is an autosomal recessive disorder of copper metabolism that causes rare diseases with significant morbidity and mortality. To our knowledge, no cases of hepatolenticular degeneration with massive cerebral infarction have been reported up to now. Here we present a case of hepatolenticular degeneration with massive cerebral infarction. Early, appropriate diagnosis and initiation of proper therapy could avoid further progression and reduce complications of the disease.

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Pathogenesis of Wilson disease

Cited by 77 publications

References 159 publications

Tc-99m TRODAT-1 SPECT is a Potential Biomarker for Restless Leg Syndrome in Patients with End-Stage Renal Disease

Tc-99m TRODAT-1 SPECT is a Potential Biomarker for Restless Leg Syndrome in Patients with End-Stage Renal Disease

Outcomes of Liver Transplant for Adults With Wilson’s Disease

Wilson's Disease Complicated with Massive Cerebral Infarction：A Case Report

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