title: [Wilson's disease and its pharmacological treatment].
abstract: Wilson's disease is an inherited copper toxicosis caused by defective putative copper transporting ATPase in the liver. Because of impaired biliary secretion, copper remains in the liver, resulting in chronic hepatic lesions including fatty metamorphosis, chronic hepatitis and cirrhosis. In the latter stage, extrapyramidal syndromes may develop with and without symptomatic hepatic lesions. Acute liver damage associated with hemolysis and deep jaundice may be the first manifestation. The majority of patients show hypoceruloplasminemia, which has been used as a screening test for the disease. A large number of mutations in the ATP7B gene have been reported. Thus, genetic diagnosis might be limitedly used to presymptomatic diagnosis of siblings when mutations are identified in an index patient. Introduction of penicillamine caused a revolution in the treatment of patients. Another chelater, trientine, is now available for those intolerant of penicillamine. Tetrathiomolibdate and zinc acetate are additional alternatives currently being tested. Hypoceruloplasminemia and further reduction after chelation therapy may be associated with iron overload. This complication is closely related with impaired transport of ferrous ion due to ferroxidase deficiency. Noncompliance and teratogenicity are other major concerns because any treatment with the agents listed above is a life long regimen. Despite various side effects of penicillamine, its teratogenicity is negligible. These data indicate that penicillamine is the first choice of drug for this disease.
authors.affiliation: Department of Medicine, Faculty of Pharmaceutical Sciences of Hokuriku University, Kanazawa 920-1181, Japan. h-hayashi@hokuriku-u.ac.jp
authors.forename: Hisao
authors.initials: H
authors.lastname: Hayashi
authors.forename: Rie
authors.initials: R
authors.lastname: Suzuki
authors.forename: Shinya
authors.initials: S
authors.lastname: Wakusawa
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D027682:Cation Transport Proteins / Q000235:genetics; D002570:Ceruloplasmin / Q000032:analysis / Q000172:deficiency; D002614:Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015913:Chelation Therapy; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D005260:Female; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D025202:Molecular Diagnostic Techniques; D008982:Molybdenum / Q000009:adverse effects / Q000627:therapeutic use; D009154:Mutation; D010396:Penicillamine / Q000009:adverse effects / Q000627:therapeutic use*; D011247:Pregnancy; D011256:Pregnancy Outcome; D019345:Zinc Acetate / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D027682:Cation Transport Proteins; D002614:Chelating Agents; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D007501:Iron; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D019345:Zinc Acetate; D010396:Penicillamine