Disease relevance of Hepatolenticular Degeneration

• The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene [1].
• Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis [2].
• Acute lymphoblastic leukemia in a patient receiving penicillamine for Wilson's disease [3].
• Within 1 week to 8 years of the onset of over liver disease the diagnosis of Wilson's disease was established, and treatment with D-penicillamine was promptly initiated in 19 patients [4].
• Trien is an unsuitable copper chelating drug in primary biliary cirrhosis, although it remains the alternative drug of choice in Wilson's disease [5].

Psychiatry related information on Hepatolenticular Degeneration

• Furthermore, dystonia must develop either during or within 3 months of a course of antipsychotic treatment, and other causes such as Wilson's disease, acute dystonia, or a conversion reaction must be ruled out [6].
• A patient with generalized dystonia due to Wilson's disease obtained marked improvement in response to smoking cannabis [7].
• Basal ganglia diseases can be of genetic origin, as in Huntington's chorea and Wilson's disease, of infectious origin as in Sydenham's chorea and postencephalitic parkinsonism, or of toxic origin as in MPTP poisoning [8].
• Psychopathology was assessed in 50 patients with the neurological form of Wilson's disease (WD-N) and in 17 asymptomatic patients (WD-A) compared to matched healthy controls and to rheumatoid arthritis (RA) control patients using The Hopkins Symptom Checklist [9].

High impact information on Hepatolenticular Degeneration

• We have previously reported the cloning of a gene that encodes a copper transporting P-type ATPase (ATP7B) which is defective in Wilson disease [10].
• We have cloned cDNAs for the rat gene (Atp7b) homologous to the human Wilson disease gene (ATP7B) and have used them to identify a partial deletion in the Atp7b gene in the LEC rat [11].
• The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene [12].
• The efficacy of oral zinc therapy as an alternative to penicillamine for Wilson's disease [13].
• The use of trientine in preventing the effects of interrupting penicillamine therapy in Wilson's disease [14].

Chemical compound and disease context of Hepatolenticular Degeneration

• D-penicillamine-induced IgA deficiency in Wilson's disease [15].
• Treatment of Wilson's disease with trientine (triethylene tetramine) dihydrochloride [16].
• Triethylene tetramine dihydrochloride (trien) is a copper chelating agent used as the alternative drug of choice in the treatment of Wilson's disease [5].
• Use of apomorphine to test for dopamine responsiveness in Wilson's disease [17].
• In this study, ratios of both the serum alkaline phosphatase to total bilirubin and aspartate transaminase to alanine transaminase were constructed to evaluate their usefulness in differentiating fulminant hepatic failure caused by Wilson's disease (n = 6) from other etiologies (n = 43) [18].
• Accordingly, individuals with Wilson disease showed elevated plasma levels of Asm, and displayed a constitutive increase of ceramide- and phosphatidylserine-positive erythrocytes [19].

Biological context of Hepatolenticular Degeneration

• We have previously performed a genetic analysis of multiply affected families to map a locus responsible for Wilson disease (WND) to a 0.3-centimorgan (cM) region within chromosome 13q14.3, between D13S31 and D13S59 [20].
• Functional characterization of missense mutations in ATP7B: Wilson disease mutation or normal variant [21]?
• Hemochromatosis and Wilson disease (WD), characterized by the excess hepatic deposition of iron and copper, respectively, produce oxidative stress and increase the risk of liver cancer [22].
• The ApoE genotype and the H1069Q mutation (the most common in Wilson's disease) status were determined by polymerase chain reaction-based mutation assays in 121 well-characterized, symptomatic index patients with Wilson's disease [23].
• Copper specifically regulates intracellular phosphorylation of the Wilson's disease protein, a human copper-transporting ATPase [24].

Anatomical context of Hepatolenticular Degeneration

• The intracellular localization of the Wilson disease gene product, ATP7B, was recently identified as the late endosomes [25].
• A sialic acid-specific O-acetylesterase in human erythrocytes: possible identity with esterase D, the genetic marker of retinoblastomas and Wilson disease [26].
• The incidence of idiopathic hemochromatosis, Wilson's disease, secondary biliary cirrhosis, portal vein thrombosis and Budd-Chiari's syndrome were less than four in both sexes [27].
• Mitochondria isolated from the livers of Wilson disease patients have evidence of lipid peroxidation, and some patients with Wilson disease have decreased hepatic and plasma levels of vitamin E. Additional investigation will be required to fully assess oxidant stress and its potential pathophysiologic role in patients with iron or copper overload [28].
• The levels of lysyl oxidase activity in cultured skin fibroblasts from these Wilson disease patients were also measured [29].

Gene context of Hepatolenticular Degeneration

• Defects in a similar gene, the copper transporting ATPase ATP7B, result in Wilson disease [30].
• Caenorhabditis elegans cDNA for a Menkes/Wilson disease gene homologue and its function in a yeast CCC2 gene deletion mutant [31].
• The Wilson disease protein (ATP7B) is a copper transporting P-type ATPase that is responsible for the efflux of hepatic copper into the bile [32].
• The unusual structure and dynamics of Atx1 suggest a copper exchange function for this protein and related domains in the Menkes and Wilson disease proteins [33].
• The association of ClC-4 and the Wilson's disease protein (ATP7B) was determined by co-immunoprecipitation [34].

Analytical, diagnostic and therapeutic context of Hepatolenticular Degeneration

• Liver biopsy specimens from 7 patients with Wilson's disease (hepatolenticular degeneration), obtained before and after 3 to 5 years of D-penicillamine therapy, were studied by electron microscopy and stereology [35].
• Ten mutations have been made in the ATP7B cDNA by site-directed mutagenesis: five Wilson disease missense mutations, two mutations originally classified as possible disease-causing mutations, two putative ATP7B normal variants, and mutation of the cysteine-proline-cysteine (CPC) motif conserved in heavy-metal-transporting P-type ATPases [21].
• To test efficacy in vivo, we added 1% thiamine to the drinking water of Long Evans Cinnamon rats, an animal model of Wilson's disease [36].
• Single-photon emission computed tomography with 123I-iodobenzamide, a dopamine D2 receptor antagonist, was employed to study dopamine D2 receptor densities in 17 patients with biochemically proved Wilson's disease and stable neurological status with therapy and in 5 age-matched control subjects [37].
• Chelation therapy with penicillamine and trientine remain effective treatment for most symptomatic hepatic and neurologic Wilson disease [38].

References