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.

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 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 in pregnancy: presentation of a case report.

2020 ◽  
Vol 19 (3) ◽  
pp. 149-152
Author(s):  
Ioannis Thanopoulos ◽  
Kalliopi Pappa
Keyword(s):  
Case Report ◽  
Wilson’S Disease ◽  
Copper Metabolism ◽  
Autosomal Recessive Disorder ◽  
Signs And Symptoms ◽  
Wilson's Disease ◽  
Management Options ◽  
Present Case Report ◽  
Progressive Liver Disease ◽  
Almost All

Wilson’s disease is a rare inherited autosomal recessive disorder of copper metabolism causing toxic hepatic and neural accumulation. The gene that regulates the disease is located on chromosome 13 (13q14.3). The signs and symptoms of Wilson’s disease vary depending on the organs that are affected by the disease with almost all the patients showing evidence of progressive liver disease. Its severity varies and is strongly associated with the time of diagnosis. In the present case report we present a rare case presenting with Wilson`s disease during pregnancy and review current management options.

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.

Copper-Induced Epigenetic Changes Shape the Clinical Phenotype in Wilson Disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Daniela Fanni ◽  
Clara Gerosa ◽  
Valeria Marina Nurchi ◽  
Rosita Cappai ◽  
Marta Mureddu ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Clinical Presentation ◽  
Clinical Phenotype ◽  
Methylation Status ◽  
Copper Metabolism ◽  
Epigenetic Factors ◽  
Genetic Changes ◽  
Illness Onset ◽  
Phenotypic Manifestation ◽  
Copper Overload

: Wilson disease is a congenital disorder of copper metabolism whose pathogenesis remains, al least in part, unknown. Subjects carrying the same genotype may show completely different phenotypes, differing for the age at illness onset or for the hepatic, neurologic or psychiatric clinical presentation. The inhability to find a unequivocal correlation between the type of mutation in the ATPase copper transporting beta (ATP7B) gene and the phenotypic manifestation, induced many authors to look for epigenetic factors interacting with the genetic changes. Here the evidences regarding the ability of copper overload to change the global DNA methylation status are discussed.

scholarly journals Systemic deletion of Atp7b modifies the hepatocytes’ response to copper overload in the mouse models of Wilson disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abigael Muchenditsi ◽  
C. Conover Talbot ◽  
Aline Gottlieb ◽  
Haojun Yang ◽  
Byunghak Kang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Respiratory Chain ◽  
Wilson Disease ◽  
Mouse Strains ◽  
Chromosomal Replication ◽  
Copper Transporter ◽  
Cu Content ◽  
Common Response ◽  
The Common ◽  
Copper Overload

AbstractWilson disease (WD) is caused by inactivation of the copper transporter Atp7b and copper overload in tissues. Mice with Atp7b deleted either globally (systemic inactivation) or only in hepatocyte recapitulate various aspects of human disease. However, their phenotypes vary, and neither the common response to copper overload nor factors contributing to variability are well defined. Using metabolic, histologic, and proteome analyses in three Atp7b-deficient mouse strains, we show that global inactivation of Atp7b enhances and specifically modifies the hepatocyte response to Cu overload. The loss of Atp7b only in hepatocytes dysregulates lipid and nucleic acid metabolisms and increases the abundance of respiratory chain components and redox balancing enzymes. In global knockouts, independently of their background, the metabolism of lipid, nucleic acid, and amino acids is inhibited, respiratory chain components are down-regulated, inflammatory response and regulation of chromosomal replication are enhanced. Decrease in glucokinase and lathosterol oxidase and elevation of mucin-13 and S100A10 are observed in all Atp7b mutant strains and reflect the extent of liver injury. The magnitude of proteomic changes in Atp7b−/− animals inversely correlates with the metallothioneins levels rather than liver Cu content. These findings facilitate identification of WD-specific metabolic and proteomic changes for diagnostic and treatment.

scholarly journals Investigation of the Wilson gene ATP7B transcriptional start site and the effect of core promoter alterations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clemens Höflich ◽  
Angela Brieger ◽  
Stefan Zeuzem ◽  
Guido Plotz
Keyword(s):  
Wilson Disease ◽  
Transcription Initiation ◽  
Transcriptional Activity ◽  
Core Promoter ◽  
Transcriptional Start Site ◽  
Copper Metabolism ◽  
Biologically Relevant ◽  
The Core ◽  
Translational Start

AbstractPathogenic genetic variants in the ATP7B gene cause Wilson disease, a recessive disorder of copper metabolism showing a significant variability in clinical phenotype. Promoter mutations have been rarely reported, and controversial data exist on the site of transcription initiation (the core promoter). We quantitatively investigated transcription initiation and found it to be located in immediate proximity of the translational start. The effects human single-nucleotide alterations of conserved bases in the core promoter on transcriptional activity were moderate, explaining why clearly pathogenic mutations within the core promoter have not been reported. Furthermore, the core promoter contains two frequent polymorphisms (rs148013251 and rs2277448) that could contribute to phenotypical variability in Wilson disease patients with incompletely inactivating mutations. However, neither polymorphism significantly modulated ATP7B expression in vitro, nor were copper household parameters in healthy probands affected. In summary, the investigations allowed to determine the biologically relevant site of ATP7B transcription initiation and demonstrated that genetic variations in this site, although being the focus of transcriptional activity, do not contribute significantly to Wilson disease pathogenesis.

scholarly journals Wilson Disease-Induced Acute Liver Failure (NWI = 13) Salvaged without Liver Transplant by Plasmapheresis

2021 ◽  
Vol 11 (01) ◽  
pp. e145-e147
Author(s):  
Nida Mirza ◽  
Ravi Bharadwaj ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Wilson Disease ◽  
Prognostic Score ◽  
Prognostic Index ◽  
Kidney Injury ◽  
Copper Metabolism ◽  
Life Saving ◽  
The Brain

AbstractWilson disease (WD) is a disorder of copper metabolism resulting in accumulation of copper in vital organs of the human body, predominantly in the liver and the brain. Acute liver failure in WD has a bad prognosis, especially with a score ≥11 in the revised WD prognostic index; emergency liver transplantation is considered the only life-saving option in this scenario. Here, we reported a girl patient with WD-induced liver failure and poor prognostic score who was rescued by plasmapheresis. She also manifested severe Coombs negative hemolytic anemia and acute kidney injury. This case report highlights the utility of an adjunctive modality besides liver transplantation for the management of fulminant liver failure caused by WD.

scholarly journals Mood symptoms Associated with CADASIL Syndrome: A Case Report

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 144-144
Author(s):  
Asad Shaikh ◽  
Joel Idowu
Keyword(s):  
Case Report ◽  
Clinical Symptoms ◽  
Psychiatric Symptoms ◽  
Small Vessel Disease ◽  
Altered Mental Status ◽  
Hereditary Disease ◽  
African American Female ◽  
Psychiatric Disturbance ◽  
Rare Type ◽  
Parietal Lobes

AbstractObjectiveTo discuss the psychiatric symptoms that are associated with CADASIL syndrome Abstract Cerebral:Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare type of hereditary disease involving the small cerebral vessels. The clinical symptoms are various and include recurrent ischemic strokes, migraine with aura, seizures with epilepsy, psychiatric problems such as mood disturbances, and progressive cognitive decline leading to dementia. This disease needs awareness amongst the psychiatrists even though it is discussed much more in neurology literature. Psychiatric symptoms are seen in 20–41% of patients with CADASIL syndrome (1, 2). Psychiatric symptoms are actually the initial presentation in 15% of the cases. (3) The psychiatric disturbance most reported are mood disturbances (9–41%) especially depression. Here a 42-year-old African American female was brought to the hospital emergency room after she was found wandering in the streets. Psychiatry was consulted for altered mental status. Upon evaluation by the psychiatric consult service she was only oriented to person, depressed, anxious and complaining of headaches. Initial CT scan showed marked small vessel disease and old lacunar infarcts in the basal ganglia and right corona radiata. Magnetic Resonance Imaging (MRI) of the brain showed acute infarcts in the right posterior frontal and right parietal lobes along with old infarcts. Her symptoms and findings on imaging were consistent with CADASIL syndrome. Once the diagnosis was confirmed and prior records were obtained patient was resumed on an antidepressant and anxiolytic.ConclusionThe purpose of this case report was to discuss psychiatric symptoms associated with CADASIL syndrome. Although there has been research showing a relationship between vascular disease and depression, a review of the literature suggests that there needs to be more research done to explore other psychiatric disturbances that may be seen with this syndrome. Psychiatric symptoms that are untreated can have the potential to further impact the quality of life therefore psychiatrists need to be aware of this syndrome in order to treat these patients promptly.References1 https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0778-8 2 http://dx.doi.org/10.32474/OJNBD.2018.01.000101 3 https://pdfs.semanticscholar.org/47f6/5952ee3c5dcf2a61345f704914b17fa8dc0d.pdf

Wilson Disease

1996 ◽  
Vol 17 (12) ◽  
pp. 448-448
Author(s):  
Philip O. Ozuah
Keyword(s):  
Biliary Excretion ◽  
Wilson Disease ◽  
Autosomal Recessive ◽  
Copper Metabolism ◽  
The Body ◽  
Hepatolenticular Degeneration ◽  
Dietary Copper ◽  
Hepatic Copper ◽  
Excess Copper ◽  
Excessive Accumulation

Wilson disease (hepatolenticular degeneration) is an autosomal recessive, inherited disorder of copper metabolism resulting in excessive accumulation of copper in the liver, brain, and other organs of the body. The manifestations of the disease are related directly to this accumulation of copper. Copper homeostasis normally is a product of the balance between intestinal absorption of dietary copper and hepatic biliary excretion of excess copper. In Wilson disease, incorporation of hepatic copper into ceruloplasmin is defective and excretion of copper in the bile is reduced. A low level of ceruloplasmin, which until a few years ago was erroneously considered to be the basis for the disease, is a consequence of the underlying metabolic defect.

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