[Wilson's disease: physiopathology, therapeutic approach and case report].
Wilson's disease is an hereditary recessive autosomal disorder which affects around five people per million inhabitants. The primary defect is localized in the liver and the disease is manifested by the accumulation of copper in tissues. The diminution of ceruloplasmin, which until a few years ago was mistakenly thought to be the pathogenetic cause of Wilson's disease, is an epiphenomenon of the underlying metabolic defect characterized by defective copper biliary excretion. There are four stages in the natural history of the disease: 1) an asymptomatic stage of hepatic copper accumulation; 2) dismission and redistribution of copper leading to hepatocellular necrosis and hemolysis; 3) extrahepatic accumulation of copper leading to the onset of cirrhosis and neurological damage; 4) stage of homeostasis following treatment but with possible irreversible neurological damage. Treatment of Wilson's disease takes the form of pharmacological, dietary and surgical therapy. Through the formation of copper and protein metal complexes D-penicillamine impoverishes copper deposits causing the reduction or disappearance of hepatic and neurological symptoms; a small percentage of patients treated develops a nephrotic syndrome requiring the compulsory suspension of the drug. In this case a valid alternative is triethylenetetramine dichlorohydrate (TETA) which provokes increased blood copper during copper diuresis. The response to pharmacological treatment is better the earlier treatment is started and the more regular its administration. Dietary intake of copper must be reduced in parallel avoiding foods with a high copper content. Liver transplant obviously leads to the "resolution" of the underlying metabolic problem in patients who develop fulminating hepatitis with hypercupremia and hemolysis and, of course, in cases of uncompensated cirrhosis which do not respond to chelating therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Istituto Medicina Interna, Università degli Studi di Torino.
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D000328:Adult; D003300:Copper / Q000378:metabolism; D006527:Hepatolenticular Degeneration / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced; D010396:Penicillamine / Q000009:adverse effects / Q000627:therapeutic use; D014266:Trientine / Q000627:therapeutic use
D003300:Copper; D010396:Penicillamine; D014266:Trientine
Morbo di Wilson. Fisiopatologia, approccio terapeutico e contributo alla casistica.