scholarly journals Histopathology of Wilson Disease

2020 ◽  
Author(s):  
Nese Karadag Soylu
Keyword(s):  
Wilson Disease ◽  
Psychiatric Symptoms ◽  
Copper Metabolism ◽  
Copper Accumulation ◽  
Serum Ceruloplasmin ◽  
Liver Histopathology ◽  
Urinary Copper ◽  
Clinical Presentations ◽  
P Type ◽  
Age Range

Wilson Disease (WD) is a genetic metabolic disease of copper metabolism. The implicated gene is ATP7B, encodes a P-type ATPase which transports copper. The resultant defective metabolism of copper results in copper accumulation in multiple tissues especially liver, eye and central nervous system. WD occurs worldwide, usually between 5 and 35 years; a wider age range is also reported. Clinical presentations are diverse and include combinations of hepatic, neurological, ophthalmic and psychiatric manifestations. Other organs or tissues may also be affected. Biochemical abnormalities such as serum ceruloplasmin and 24-h urinary copper excretion are important for the diagnosis but are not always abnormal in WD. The liver histopathology has several different patterns from mild nonspecific changes to acute fulminant hepatitis and cirrhosis. Copper histochemistry is helpful in diagnosis. Genetic testing is another diagnostic tool. It is important to diagnose WD because it is fatal when overlooked, curable when diagnosed. The diagnosis should be keep in mind at all ages in patients with hepatic disease, neurological disease, or psychiatric symptoms.

Biochemical and molecular characterisation of neurological Wilson disease

2018 ◽  
Vol 55 (9) ◽  
pp. 587-593 ◽  
Author(s):  
Go Hun Seo ◽  
Yoon-Myung Kim ◽  
Seak Hee Oh ◽  
Sun Ju Chung ◽  
In Hee Choi ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Age At Onset ◽  
Copper Metabolism ◽  
Favourable Outcome ◽  
Treatment Needs ◽  
Serum Ceruloplasmin ◽  
Urinary Copper ◽  
Genetic Features ◽  
Distinct Disease ◽  
Serum Aspartate Aminotransferase

BackgroundTo identify biochemical and genetic features that characterise neurological Wilson disease as a distinct disease subgroup.MethodsDetailed biochemical profiles and genotypic characteristics of neurological (86 patients) and hepatic subgroups (233 patients) from 368 unrelated Korean families were analysed.ResultsCompared with patients in the hepatic subgroup, patients in the neurological subgroup had a later age at onset, a higher proportion with Kayser-Fleischer rings and higher serum creatinine levels, and a lower proportion with favourable outcome (62% vs 80%, P<0.016). At diagnosis, the neurological subgroup had lower serum ceruloplasmin (3.1±2.1 mg/dL vs 4.2±3.2 mg/dL, P<0.001), total copper (26.4±13.8 µg/dL vs 35.8±42.4 µg/dL, P=0.005), free copper (17.2±12.5 µg/dL vs 23.5±38.2 µg/dL, P=0.038) and urinary copper (280.9±162.9 µg/day vs 611.1±1124.2 µg/day, P<0.001) levels. Serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase and total bilirubin levels, as well as prothrombin time, were also lower in the neurological subgroup. Liver cirrhosis was more common but mostly compensated in the neurological subgroup. Frameshift, nonsense or splice-site ATP7B mutations and mutations in transduction or ATP hinge domains (2.4% vs 23.1%, P=0.006) were less common in the neurological subgroup.ConclusionThe neurological subgroup had distinct clinical, biochemical and genetic profiles. Further studies are required to identify the factors, with or without association with copper metabolism, underlying the neurological presentation for which treatment needs to be targeted to improve the clinical outcome of this subgroup.

Evaluation and grading of Kayser–Fleischer ring in Wilson disease by Scheimpflug camera

2020 ◽  
pp. 112067212093102
Author(s):  
Cumali Degirmenci ◽  
Melis Palamar
Keyword(s):  
Wilson Disease ◽  
Corneal Thickness ◽  
Anterior Segment ◽  
Serum Ceruloplasmin ◽  
Endothelial Surface ◽  
Ceruloplasmin Level ◽  
Urinary Copper ◽  
Scheimpflug Imaging ◽  
Anterior Segment Parameters ◽  
Grade 3

Purpose: Evaluation the anterior segment parameters of Wilson disease patients with Kayser–Fleischer ring, the diagnostic power of Scheimpflug imaging for Kayser–Fleischer ring and suggest a scoring system. Materials and Methods: A total of 44 eyes of 22 Wilson disease patients with Kayser–Fleischer ring and 40 right eyes of 40 healthy age matched subjects were enrolled to the study. Serum ceruloplasmin and urine copper/24 hours levels were recorded. Anterior segment parameters including steep and flat keratometry, corneal thickness at central, 2, 4, 6, 8 and 10 mm, anterior chamber angle width, volume and depth, corneal volume, pupillary diameter were evaluated by Scheimpflug imaging. Images of cornea were scored according to Kayser–Fleischer ring size. Results: Serum ceruloplasmin level was below 10 mg/dL in 17 patients and was 12, 18.5, 20, 22, 37 mg/dl in the remaining five patients. Urinary copper/24 hours was 249.55 ± 304.14 (23–1050) µg/day. Central corneal thickness and corneal thickness at 2 mm were statistically different ( p values 0.02, 0.04, respectively). Scheimpflug images apparently showed Kayser–Fleischer ring as a hyper-reflective band at the corneal endothelial surface. Kayser–Fleischer ring in 24 eyes was grade 1, 16 eyes were grade 2 and 4 eyes were grade 3. Conclusion: Scheimpflug imaging seems to be a helpful diagnostic tool for detecting and grading the Kayser–Fleischer ring. Corneal thickness in Wilson disease patients with Kayser–Fleischer ring tends to be higher, so that the possible affection in corneal thickness should be kept in mind for clinical evaluation of these patients.

scholarly journals ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease

2018 ◽  
Author(s):  
Daniel F. Wallace ◽  
James S. Dooley
Keyword(s):  
Wilson Disease ◽  
Genomic Sequence ◽  
Genetic Disorder ◽  
Copper Metabolism ◽  
Genetic Studies ◽  
Population Prevalence ◽  
Atpase Gene ◽  
Prevalence Estimates ◽  
The Uk ◽  
P Type

AbstractWilson disease (WD) is a genetic disorder of copper metabolism caused by variants in the copper transporting P-type ATPase gene ATP7B. Estimates for WD population prevalence vary with 1 in 30,000 generally quoted. However, some genetic studies have reported much higher prevalence rates. The aim of this study was to estimate the population prevalence of WD and the pathogenicity/penetrance of WD variants by determining the frequency of ATP7B variants in a genomic sequence database. A catalogue of WD-associated ATP7B variants was constructed and then frequency information for these was extracted from the gnomAD dataset. Pathogenicity of variants was assessed by (a) comparing gnomAD allele frequencies against the number of reports for variants in the WD literature and (b) using variant effect prediction algorithms. 231 WD-associated ATP7B variants were identified in the gnomAD dataset, giving an initial estimated population prevalence of around 1 in 2400. After exclusion of WD-associated ATP7B variants with predicted low penetrance, the revised estimate showed a prevalence of around 1 in 20,000, with higher rates in the Asian and Ashkenazi Jewish populations. Reanalysis of other recent genetic studies using our penetrance criteria also predicted lower population prevalences for WD in the UK and France than had been reported. Our results suggest that differences in variant penetrance can explain the discrepancy between reported epidemiological and genetic prevalences of WD. They also highlight the challenge in defining penetrance when assigning causality to some ATP7B variants.

scholarly journals Zinc Monotherapy as an Alternative Treatment Option for Decompensated Liver Disease due to Wilson Disease?

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Hansa Haftu ◽  
Mohammed Mustefa ◽  
Teklu Gebrehiwot
Keyword(s):  
Liver Disease ◽  
Treatment Option ◽  
Alternative Treatment ◽  
Wilson Disease ◽  
Copper Metabolism ◽  
Variable Degree ◽  
Decompensated Liver Disease ◽  
Serum Ceruloplasmin ◽  
Asymptomatic Patients ◽  
Alternative Treatment Option

Background. Wilson disease is a rare metabolic disorder involving copper metabolism, and patients may present with a variable degree of hepatic, neurologic, and psychiatric manifestations. In the case of hepatic presentation, treatment is usually initiated with potentially toxic copper chelators (D-penicillamine or Trenton). Although zinc is of low toxicity and low cost for treatment of Wilson disease, it has been limited to the adjunctive as a single maintenance drug or for asymptomatic patients. The use of zinc monotherapy in patients suffering from a severe liver disease was not well studied. In our case report, we describe a pediatric patient who presented with liver failure and the use of zinc monotherapy in patients with severe hepatic manifestations. Case presentation. A 15-year-old male patient from Ethiopia presented with generalized body swelling (edema and ascites) with yellowish discoloration of his eyes and easy fatigability. He had hyperbilirubinemia, coagulopathy, hypoalbuminemia, and deranged liver enzymes. He had a Keyser–Fleischer ring visible with the naked eye, which was confirmed by slit-lamp examination. He had very low serum ceruloplasmin (<8 mg/L) and high 24-hour urine copper (150 mcg/dl). In accordance with the scoring system proposed by the 8th International Meeting on Wilson Disease and Menkes Disease, a diagnosis of Wilson disease was made. Zinc monotherapy with low copper diet was initiated for decompensated liver disease due to Wilson disease because of the inaccessibility of chelators (D-penicillamine or Trientine). After months of treatment with zinc, the patient experienced normalization of hepatic synthetic function and resolution of hypoalbuminemia and coagulopathy. The patient had also clinically stabilized (ascites, lower extremity swelling, edema, and jaundice were improved. Currently, the patient is on follow-up almost for the last four years in the gastrointestinal clinic. Conclusion. Our case shows that zinc has the potential for treatment in improving liver function. Though zinc has its own side effects, it is important and maybe an alternative treatment option in those with limited resources (not able to access chelators). This example hopefully will encourage future investigations and researches on zinc monotherapy for treating symptomatic decompensated hepatic Wilson disease.

scholarly journals Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments

1997 ◽  
Vol 326 (3) ◽  
pp. 897-902 ◽  
Author(s):  
Xiao-Li YANG ◽  
Naoyuki MIURA ◽  
Yoshihiko KAWARADA ◽  
Kunihiko TERADA ◽  
Konstantin PETRUKHIN ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Wilson Disease ◽  
Intracellular Transport ◽  
Copper Metabolism ◽  
Copper Transporter ◽  
Wilson Disease Protein ◽  
Disease Protein ◽  
Human Disorders ◽  
P Type ◽  
Cellular Compartments

Copper is an essential trace element in prokaryotes and eukaryotes and is strictly regulated by biological mechanisms. Menkes and Wilson diseases are human disorders that arise from disruption of the normal process of copper export from the cytosol to the extracellular environment. Recently a gene for Wilson disease (WD) (also named the ATP7B gene) was cloned. This gene encodes a copper transporter of the P-type ATPase. We prepared monoclonal and polyclonal anti-(WD protein) antibodies and characterized the full-length WD protein as well as a shorter form that is produced by alternative splicing in the human brain. We found that the WD protein is localized mainly in the Golgi apparatus, whereas the shorter form is present in the cytosol. These results suggest that the alternative WD proteins act as key regulators of copper metabolism, perhaps by performing distinct roles in the intracellular transport and export of copper.

scholarly journals Wilson Disease: Canadian Perspectives on Presentation And Outcomes from an Adult Ambulatory Setting

2012 ◽  
Vol 26 (6) ◽  
pp. 333-339 ◽  
Author(s):  
A Moores ◽  
SH Fox ◽  
AE Lang ◽  
GM Hirschfield
Keyword(s):  
Basal Ganglia ◽  
Wilson Disease ◽  
Copper Metabolism ◽  
Retrospective Chart Review ◽  
Complete Recovery ◽  
Initial Therapy ◽  
Ambulatory Setting ◽  
Venous Flow ◽  
Variceal Bleed ◽  
Urinary Copper

BACKGROUND: Wilson disease (WD) is a rare disorder of copper metabolism.OBJECTIVE: To describe the authors’ clinical experience with a cohort of 48 adult patients followed in an ambulatory setting.METHODS: A retrospective chart review of patients with a diagnosis of WD was performed.RESULTS: Fifty-nine charts were identified and 11 were excluded on further review. At diagnosis, 14 patients were asymptomatic, with 13 hepatic, 15 neurological and six mixed hepatic/neurological presentations. Ceruloplasmin levels were low (<0.20 g/L) in 94%, and 24 h urinary copper levels high (>0.60 μmol/L) in 95% of cases. D-penicillamine was the most common initial therapy (48%), with zinc the most common at review (65%). Overall, biopsy and ultrasound reports documented cirrhosis in 53%. Portal hypertension, defined as splenomegaly (>12.0 cm), reversed portal venous flow on ultrasound or varices/gastropathy on endoscopy was seen in 63%. At last review, 39% had elevated aspartate aminotransferase (>34 U/L) and/or alanine aminotransferase levels (>40 U/L). One death and one transplant occurred, while three patients had encephalopathy, two became jaundiced, two developed ascites and one experienced variceal bleed. Of 21 neurological presenting patients, 14 improved compared with baseline, with four making almost complete recovery. Eleven patients experienced documented episodes of neurological decline, including four with non-neurological presentation. Diagnostic magnetic resonance imaging showed basal ganglia (64%), brainstem (64%) abnormalities and atrophy (36%); follow-up showed basal ganglia lesions (50%) and atrophy (55%).CONCLUSION: WD is a diverse chronic disease with generally favourable outcomes for patients who respond to initial therapy, which can be managed predominantly in an ambulatory setting.

scholarly journals Wilson disease and psychiatric symptoms: A brief case report

2019 ◽  
Vol 32 (3) ◽  
pp. e100066
Author(s):  
Margarita Guerrero-Jiménez ◽  
Carmen Maura Carrillo de Albornoz Calahorro ◽  
Luis Gutierrez Rojas
Keyword(s):  
Wilson Disease ◽  
Psychiatric Symptoms ◽  
Genetic Disorder ◽  
Neuropsychiatric Symptoms ◽  
Copper Metabolism ◽  
Short Review ◽  
Neurological Damage ◽  
Delay In Diagnosis ◽  
Causal Treatment ◽  
Delay Of Diagnosis

Wilson disease (WD) is an uncommon recessive genetic disorder affecting copper metabolism. Cardiac, neurological, hepatic and renal manifestations are well defined, nevertheless approximately 30% of patients debut with neuropsychiatric symptoms. These psychiatric alterations resulting from the accumulation of this heavy metal in the basal ganglia are some how less specific. We present a short review of psychiatric symptoms of WD and describe a case of a 37-year-old woman diagnosed with WD who presented neuropsychiatric symptoms and had a consequent delay in diagnosis and causal treatment. Patients who develop WD starting with a predominance of neuropsychiatric symptoms tend to manifest hepatic symptoms later, therefore have a longer delay of diagnosis and a poorer outcome than patients with hepatic symptoms. An early diagnosis of WD can avoid irreversible neurological damage.

scholarly journals Wilson’s Disease Presenting in Late Adult Life

2021 ◽  
pp. 142-146
Author(s):  
Wafa AlDhaleei ◽  
Maryam AlAhmad ◽  
Ibrahim Alhosani
Keyword(s):  
Wilson’S Disease ◽  
Adult Life ◽  
Copper Metabolism ◽  
Wilson's Disease ◽  
Serum Copper ◽  
Hepatic Copper ◽  
Urinary Copper ◽  
Clinical Presentations ◽  
Function Impairment ◽  
Diagnostic Management

Wilson’s disease (WD) is an autosomal recessive disease affecting the copper metabolism resulting in various clinical presentations. Diagnosis includes the presence of low serum copper and ceruloplasmin concentrations, increased urinary copper excretion, and/or increased hepatic copper concentrations. Yet, genetic testing remains diagnostic. Management includes copper chelating agents and liver transplant in advance cases. We report a case of WD presenting with liver function impairment in late adult life and started on treatment. Therefore, early diagnosis and treatment of WD can prevent related complications.

scholarly journals WILSON’S DISEASE WITH AYURVEDIC APPROACH - A CASE STUDY

2020 ◽  
Vol 8 (10) ◽  
pp. 4910-4916
Author(s):  
Renu Rani ◽  
Satyawati Rathia ◽  
Kori V. K. ◽  
Patel K. S.
Keyword(s):  
Wilson Disease ◽  
Liver Toxicity ◽  
Symptomatic Relief ◽  
Treatment Protocol ◽  
Copper Metabolism ◽  
Female Child ◽  
Copper Accumulation ◽  
Func Tion

Wilson disease is a rare, inherited autosomal recessive disease of copper metabolism. Loss of ATP7B func-tion leads various grades of reduced biliary excretion of copper accumulation and toxicity of copper in the liver, brain and other tissues results in liver toxicity and other myriad manifestations of the disease. In clas-sics there is no exact description of the disease entity which exactly matches the feature of Wilson disease, but it can be correlated with Sahaja Vyadhi or Janamjata Vyadhi. A 16-year-old female child diagnosed with Wilson disease complaints of improper gait, altered speech, chronic constipation and altered mental level etc. Investigation shows S. Ceruloplasmin- 0.4mg/dl, S. copper- within normal limit, slit lamp study for KF ring was positive. This patient was treated with Ayurvedic procedures i.e. Abhyanga, Swedana, Bas-ti and Nasya along with oral medication. After two treatment protocol patient got symptomatic relief in clin-ical features. So, it can be concluded that quality of life (QOL) of patients with chronic disease can be im-proved with the help of internal Ayurvedic medication along with Panchkarma procedure.

scholarly journals Biochemical markers for the diagnosis and monitoring of Wilson Disease

2019 ◽  
Vol 40 (2) ◽  
pp. 59-77 ◽  
Keyword(s):  
Wilson Disease ◽  
Biochemical Markers ◽  
Dna Analysis ◽  
Clinical Symptoms ◽  
Psychiatric Symptoms ◽  
Copper Metabolism ◽  
Copper Transporter ◽  
Copper Excretion ◽  
Progressive Liver Disease ◽  
Almost All

Wilson disease (WD) is an autosomal recessively-inherited disorder of copper metabolism and characterised by a pathological accumulation of copper. The ATP7B gene encodes for a transmembrane copper transporter essential for biliary copper excretion. Depending on time of diagnosis, severity of disease can vary widely. Almost all patients show evidence of progressive liver disease. Neurological impairments or psychiatric symptoms are common in WD patients not diagnosed during adolescence. WD is a treatable disorder, and early treatment can prevent the development of symptoms in patients diagnosed while still asymptomatic. This is why the early diagnosis of WD is crucial. The diagnosis is based on clinical symptoms, abnormal measures of copper metabolism and DNA analysis. Available treatment includes chelators and zinc salts which increase copper excretion and reduce copper uptake. In severe cases, liver transplantation is indicated and accomplishes a phenotypic correction of the hepatic gene defect. Recently, clinical development of the new copper modulating agent tetrathiomolybdate has started and direct genetic therapies are being tested in animal models. The following review focuses especially on biochemical markers and how they can be utilised in diagnosis and drug monitoring.

Sign in / Sign up

Export Citation Format

Share Document