Wilson disease
Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism, resulting in pathological accumulation of copper in many organs and tissues. The hallmarks of the disease are the presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings. The leading neu...
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description | Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism, resulting in pathological accumulation of copper in many organs and tissues. The hallmarks of the disease are the presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings. The leading neurologic symptoms in WD are dysathria, dyspraxia, ataxia, and Parkinsonian-like extrapyramidal signs. Changes in the basal ganglia in brain magnetic resonance imaging (MRI) are characteristic features of the disease. In presence of liver cirrhosis, some features may resemble hepatic encephalopathy. Symptoms and MRI abnormalities may be fully reversible on treatment with zinc or copper chelators. Improvement can be monitored by serial recording of brain-stem-evoked responses. The basic defect is an impaired trafficking of copper in hepatocytes. ATP7B is the gene product of the WD gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting copper into the secretory pathway for incorporation into apoceruloplasmin and excretion into the bile. While about 40% of patients preset with neurologic symptoms, little is known about the role of copper and ATP7B in the central nervous system. In some brain areas, like in the pineal gland, ATP7B is expressed and functionally active. Increasing evidence supports an important role for metals in neurobiology. Two proteins related to neurodegeneration are copper-binding proteins (1) the amyloid precursor protein (APP), a protein related to Alzheimer's disease, and (2) the Prion protein, related to Creutzfeldt-Jakob disease. A major source of free-radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. APP is a major regulator of neuronal copper homeostasis and has a copper-binding domain (CuBD). The surface location of this site, structural homology of CuBD to copper chaperones, and the role of APP in neuronal copper homeostasis are consistent with the CuBD acting as a neuronal metallotransporter. There are several copper-containing enzymes in the brain, like dopamine beta hydroxylase or Cu/Zn superoxide dismutase (SOD1). Their function may be altered because of copper overload. WD appears to be associated with a dopaminergic deficit. Mutations in the SOD1gene cause familial amyotrophic lateral sclerosis. Survival of transgenic mice with a mutant SOD1 which fails to incorporate Cu((2+)) in its active si |
doi_str_mv | 10.1007/s11011-005-7910-8 |
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The hallmarks of the disease are the presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings. The leading neurologic symptoms in WD are dysathria, dyspraxia, ataxia, and Parkinsonian-like extrapyramidal signs. Changes in the basal ganglia in brain magnetic resonance imaging (MRI) are characteristic features of the disease. In presence of liver cirrhosis, some features may resemble hepatic encephalopathy. Symptoms and MRI abnormalities may be fully reversible on treatment with zinc or copper chelators. Improvement can be monitored by serial recording of brain-stem-evoked responses. The basic defect is an impaired trafficking of copper in hepatocytes. ATP7B is the gene product of the WD gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting copper into the secretory pathway for incorporation into apoceruloplasmin and excretion into the bile. While about 40% of patients preset with neurologic symptoms, little is known about the role of copper and ATP7B in the central nervous system. In some brain areas, like in the pineal gland, ATP7B is expressed and functionally active. Increasing evidence supports an important role for metals in neurobiology. Two proteins related to neurodegeneration are copper-binding proteins (1) the amyloid precursor protein (APP), a protein related to Alzheimer's disease, and (2) the Prion protein, related to Creutzfeldt-Jakob disease. A major source of free-radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. APP is a major regulator of neuronal copper homeostasis and has a copper-binding domain (CuBD). The surface location of this site, structural homology of CuBD to copper chaperones, and the role of APP in neuronal copper homeostasis are consistent with the CuBD acting as a neuronal metallotransporter. There are several copper-containing enzymes in the brain, like dopamine beta hydroxylase or Cu/Zn superoxide dismutase (SOD1). Their function may be altered because of copper overload. WD appears to be associated with a dopaminergic deficit. Mutations in the SOD1gene cause familial amyotrophic lateral sclerosis. Survival of transgenic mice with a mutant SOD1 which fails to incorporate Cu((2+)) in its active site was improved by copper depletion. Wilson disease (WD) is an autosomal recessive inherited disorder in which copper pathologically accumulates primarily within the liver and subsequently in the neurologic system and many other organs and tissues. Presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings are the hallmarks of the disease.</description><identifier>ISSN: 0885-7490</identifier><identifier>EISSN: 1573-7365</identifier><identifier>DOI: 10.1007/s11011-005-7910-8</identifier><identifier>PMID: 16382340</identifier><identifier>CODEN: MBDIEE</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Animals ; Biological and medical sciences ; Brain - pathology ; Cardiovascular system ; Copper - metabolism ; Errors of metabolism ; Hepatolenticular Degeneration - diagnosis ; Hepatolenticular Degeneration - metabolism ; Hepatolenticular Degeneration - pathology ; Hepatolenticular Degeneration - psychology ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Lipids (lysosomal enzyme disorders, storage diseases) ; Liver - metabolism ; Medical sciences ; Metabolic diseases ; Neurology ; Radiodiagnosis. Nmr imagery. Nmr spectrometry</subject><ispartof>Metabolic brain disease, 2005-12, Vol.20 (4), p.295-302</ispartof><rights>2006 INIST-CNRS</rights><rights>Springer Science + Business Media, Inc. 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-94bc954de5fdc6a72ea232994aa3d2e8468cb0c942531868ab6853e755b682103</citedby><cites>FETCH-LOGICAL-c387t-94bc954de5fdc6a72ea232994aa3d2e8468cb0c942531868ab6853e755b682103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>310,311,315,781,785,790,791,23935,23936,25145,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17446709$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16382340$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KITZBERGER, Reinhard</creatorcontrib><creatorcontrib>MADL, Christian</creatorcontrib><creatorcontrib>FERENCI, Peter</creatorcontrib><title>Wilson disease</title><title>Metabolic brain disease</title><addtitle>Metab Brain Dis</addtitle><description>Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism, resulting in pathological accumulation of copper in many organs and tissues. The hallmarks of the disease are the presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings. The leading neurologic symptoms in WD are dysathria, dyspraxia, ataxia, and Parkinsonian-like extrapyramidal signs. Changes in the basal ganglia in brain magnetic resonance imaging (MRI) are characteristic features of the disease. In presence of liver cirrhosis, some features may resemble hepatic encephalopathy. Symptoms and MRI abnormalities may be fully reversible on treatment with zinc or copper chelators. Improvement can be monitored by serial recording of brain-stem-evoked responses. The basic defect is an impaired trafficking of copper in hepatocytes. ATP7B is the gene product of the WD gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting copper into the secretory pathway for incorporation into apoceruloplasmin and excretion into the bile. While about 40% of patients preset with neurologic symptoms, little is known about the role of copper and ATP7B in the central nervous system. In some brain areas, like in the pineal gland, ATP7B is expressed and functionally active. Increasing evidence supports an important role for metals in neurobiology. Two proteins related to neurodegeneration are copper-binding proteins (1) the amyloid precursor protein (APP), a protein related to Alzheimer's disease, and (2) the Prion protein, related to Creutzfeldt-Jakob disease. A major source of free-radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. APP is a major regulator of neuronal copper homeostasis and has a copper-binding domain (CuBD). The surface location of this site, structural homology of CuBD to copper chaperones, and the role of APP in neuronal copper homeostasis are consistent with the CuBD acting as a neuronal metallotransporter. There are several copper-containing enzymes in the brain, like dopamine beta hydroxylase or Cu/Zn superoxide dismutase (SOD1). Their function may be altered because of copper overload. WD appears to be associated with a dopaminergic deficit. Mutations in the SOD1gene cause familial amyotrophic lateral sclerosis. Survival of transgenic mice with a mutant SOD1 which fails to incorporate Cu((2+)) in its active site was improved by copper depletion. Wilson disease (WD) is an autosomal recessive inherited disorder in which copper pathologically accumulates primarily within the liver and subsequently in the neurologic system and many other organs and tissues. Presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings are the hallmarks of the disease.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain - pathology</subject><subject>Cardiovascular system</subject><subject>Copper - metabolism</subject><subject>Errors of metabolism</subject><subject>Hepatolenticular Degeneration - diagnosis</subject><subject>Hepatolenticular Degeneration - metabolism</subject><subject>Hepatolenticular Degeneration - pathology</subject><subject>Hepatolenticular Degeneration - psychology</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Lipids (lysosomal enzyme disorders, storage diseases)</subject><subject>Liver - metabolism</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Neurology</subject><subject>Radiodiagnosis. Nmr imagery. 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Nmr imagery. Nmr spectrometry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KITZBERGER, Reinhard</creatorcontrib><creatorcontrib>MADL, Christian</creatorcontrib><creatorcontrib>FERENCI, Peter</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Metabolic brain disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KITZBERGER, Reinhard</au><au>MADL, Christian</au><au>FERENCI, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wilson disease</atitle><jtitle>Metabolic brain disease</jtitle><addtitle>Metab Brain Dis</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>20</volume><issue>4</issue><spage>295</spage><epage>302</epage><pages>295-302</pages><issn>0885-7490</issn><eissn>1573-7365</eissn><coden>MBDIEE</coden><abstract>Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism, resulting in pathological accumulation of copper in many organs and tissues. The hallmarks of the disease are the presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings. The leading neurologic symptoms in WD are dysathria, dyspraxia, ataxia, and Parkinsonian-like extrapyramidal signs. Changes in the basal ganglia in brain magnetic resonance imaging (MRI) are characteristic features of the disease. In presence of liver cirrhosis, some features may resemble hepatic encephalopathy. Symptoms and MRI abnormalities may be fully reversible on treatment with zinc or copper chelators. Improvement can be monitored by serial recording of brain-stem-evoked responses. The basic defect is an impaired trafficking of copper in hepatocytes. ATP7B is the gene product of the WD gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting copper into the secretory pathway for incorporation into apoceruloplasmin and excretion into the bile. While about 40% of patients preset with neurologic symptoms, little is known about the role of copper and ATP7B in the central nervous system. In some brain areas, like in the pineal gland, ATP7B is expressed and functionally active. Increasing evidence supports an important role for metals in neurobiology. Two proteins related to neurodegeneration are copper-binding proteins (1) the amyloid precursor protein (APP), a protein related to Alzheimer's disease, and (2) the Prion protein, related to Creutzfeldt-Jakob disease. A major source of free-radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. APP is a major regulator of neuronal copper homeostasis and has a copper-binding domain (CuBD). The surface location of this site, structural homology of CuBD to copper chaperones, and the role of APP in neuronal copper homeostasis are consistent with the CuBD acting as a neuronal metallotransporter. There are several copper-containing enzymes in the brain, like dopamine beta hydroxylase or Cu/Zn superoxide dismutase (SOD1). Their function may be altered because of copper overload. WD appears to be associated with a dopaminergic deficit. Mutations in the SOD1gene cause familial amyotrophic lateral sclerosis. Survival of transgenic mice with a mutant SOD1 which fails to incorporate Cu((2+)) in its active site was improved by copper depletion. Wilson disease (WD) is an autosomal recessive inherited disorder in which copper pathologically accumulates primarily within the liver and subsequently in the neurologic system and many other organs and tissues. Presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings are the hallmarks of the disease.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>16382340</pmid><doi>10.1007/s11011-005-7910-8</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Biological and medical sciences Brain - pathology Cardiovascular system Copper - metabolism Errors of metabolism Hepatolenticular Degeneration - diagnosis Hepatolenticular Degeneration - metabolism Hepatolenticular Degeneration - pathology Hepatolenticular Degeneration - psychology Humans Investigative techniques, diagnostic techniques (general aspects) Lipids (lysosomal enzyme disorders, storage diseases) Liver - metabolism Medical sciences Metabolic diseases Neurology Radiodiagnosis. Nmr imagery. Nmr spectrometry |
title | Wilson disease |
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