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Copper and liver disease

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Abstract

There has been some limited progress in the understanding of the basic defect in Wilson disease and the gene concerned has been located to the chromosome region 13q14. Treatment with zinc has emerged as a definite alternative to penicillamine administration and some shortcomings and/or hazards of both forms of therapy have emerged as their modes of action have been studied more carefully. Tetrathimolybdate may have a place in treatment, espacially when rapid complexing of copper is important. Hepatic copper accumulation occurs in a number of cholestatic diseases and they play an important part in pathogenesis and can occasionally lead to neurological toxic effects. Copper overload in the new-born period when biliary excretion of copper is inefficient may establish a vicious cyle of copper accumulation and liver damage in Indian childhood cirrhosis and less frequently in babies in other countries.

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Abbreviations

CP:

caeruloplasmin

MT:

metallothionein

TTM:

tetrathiomolybdate

WD:

Wilson disease

References

  1. Aagenaes O (1974) Hereditary recurrent cholestasis with lymphoedema: two new families. Acta Paediatr Scand 63:465–471

    PubMed  Google Scholar 

  2. Alagille D, Estrada A, Haochouel M, Gautier M, Odievre M, Dommeregues JP (1987) Syndrome paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia)—review of 80 cases. J Pediatr 110:195–200

    PubMed  Google Scholar 

  3. Barrow L, Tanner MS (1987) Penicillamine in Indian childhood cirrhosis. Lancet II:513–514

    Google Scholar 

  4. Biempica L, Rauch H, Quintana N, Sternlieb I (1988) Morphologic and chemical studies on a murine mutation (toxic milk mice) resulting in hepatic copper toxicosis. Lab Invest 59: 500–508

    PubMed  Google Scholar 

  5. Bowcock AM, Farrer LA, Hebert JM, Agger M, Sternlieb I, Scheinberg IH, Buys CH, Scheffer H, Frydman M, Chajek-Saul T (1988) Predicting genotypes at loci for autosomal recessive disorders using linked genetic markers: application to Wilson's disease. Hum Genet 79:109–117

    PubMed  Google Scholar 

  6. Brewer GJ, Terry CA, Aisen AM, Hill GM (1987) Worsening of neurologic syndrome in patients with Wilson's disease with initial penicillamine therapy. Arch Neurol 44:490–493

    PubMed  Google Scholar 

  7. Brewer GJ, Yuzbasiyan-Gurkan V (1989) Wilson's disease: an update, with emphasis on new approaches to treatment. Dig Dis 7:178–193

    PubMed  Google Scholar 

  8. Brewer GJ, Yuzbasiyan-Gurkan V, Lee DY (1990) Human and canine inherited copper toxicosis: copper balance regulation and molecular genetics of its impairment. In: Tomita H (ed) Trace elements in clinical medicine. Springer, Berlin Heidelberg New York Tokyo, pp 283–287

    Google Scholar 

  9. Dameron CT, Harris ED (1987) Regulation of aortic CuZn-superoxide dismutase with copper: caeruloplasmin and albumin re-activate and transfer copper to the enzyme in culture. Biochem J 248:669–675

    PubMed  Google Scholar 

  10. Dameron CT, Harris ED (1987) Regulation of aortic CuZn-superoxide dismutase with copper: effects in vivo. Biochem J 248:663–668

    PubMed  Google Scholar 

  11. Danks DM (1989) Disorders of copper transport. In: Scriver CR, Beaudet AL, Sly WS, Vallee D (eds) The metabolic basis of inherited disease. 6th edn. McGraw Hill, New York, pp 1411–1431

    Google Scholar 

  12. Danks DM (1990) Copper-induced dystonia secondary to cholestatic liver disease. Lancet I:410

    Google Scholar 

  13. Danks DM, Campbell PE, Jack I, Rogers J, Smith AL (1977) Studies of the aetiology of neonatal hepatitis and biliary atresia. Arch Dis Child 52:360–367

    PubMed  Google Scholar 

  14. Danks DM, Campbell PE, Smith AL, Rogers J (1977) Prognosis of babies with neonatal hepatitis. Arch Dis Child 52: 368–372

    PubMed  Google Scholar 

  15. Danks DM, Metz G, Sewell R, Prewett EJ (1990) Wilson's disease as a cause of cirrhosis in adults with no neurological abnormalities. Br Med J 301:331–332

    Google Scholar 

  16. Ede RJ, Nazer H, Mowat AP, Williams R (1986) Wilson's disease: clinical presentation and use of prognostic index. Gut 27: 1377–1381

    PubMed  Google Scholar 

  17. Editorial (1989) Homing in on Wilson's disease. Lancet I:822–823

  18. Epstein O, Sherlock S (1981) Is Wilson's disease caused by a controller gene mutation resulting in perpetuation of the fetal mode of copper metabolism into childhood? Lancet I:303–305

    Google Scholar 

  19. Gooneratne SR, Howell JMcC, Gawthorne JM (1981) Intravenous administration of thiomolybdate for the prevention and treatment of chronic copper poisoning in sheep. Br J Nutr 46: 457–468

    PubMed  Google Scholar 

  20. Harper PL, Walshe JM (1986) Reversible pancytopenia secondary to treatment with tetrathiomolybdate. Br J Haematol 64:851–853

    PubMed  Google Scholar 

  21. Henriksen NT, Drablos P-A, Aagenaes O (1981) Cholestatic jaundice in infancy. The importance of familial and genetic factors in aetiology and prognosis. Arch Dis Child 56:622–627

    PubMed  Google Scholar 

  22. Hoogenraad TU, Van Hattum J, Van den Hamer CJA (1987) Management of Wilson's disease with zinc sulphate. Experience in a series of 27 patients. J Neurol Sci 77:137–146

    PubMed  Google Scholar 

  23. Iyengar V, Brewer GJ, Dick RD, Owyang C (1988) Studies of cholecystokinin stimulated biliary secretions reveal a high molecular weight copper-binding substance in normal subjects that is absent in patients with Wilson's disease. J Lab Clin Med 111:267–277

    PubMed  Google Scholar 

  24. Kincaid RL, White CL (1988) The effects of ammonium tetrathiomolybdate intake on tissue copper and molybdenum in pregnant ewes and lambs. J Amin Sci 66:3252–3258

    Google Scholar 

  25. Lefkowitch JH, Honig CL, King ME, Hagstrom JWC (1982) Hepatic copper overload and features of Indian childhood cirrhosis on an American sibship. N Engl J Med 307:271–277

    PubMed  Google Scholar 

  26. Maggiore G, De Giacomo C, Sessa F, Burgio GR (1987) Idiopathic hepatic copper toxicosis in a child. J Pediatr Gastroenterol Nutr 6:980–983

    PubMed  Google Scholar 

  27. Mason J, McQuaid A, Pheiffer H (1989) Can Wilson's disease patients be decoppered? Lancet I:1455

    Google Scholar 

  28. McArdle HJ, Kyriakou P, Grimes A, Mercer JFB, Danks DM (1990) The effect of D-penicillamine on metallothionein mRNA levels and copper distribution in mouse hepatocytes. Chem Biol Interact (in press)

  29. Muller-Hocker J, Meyer U, Wiebecke B, Hubner G, Eife R, Kellner M, Schramel P (1988) Copper storage disease of the liver and chronic dietary copper intoxication in two further German infants mimicking Indian childhood cirrhosis. Pathol Res Pract 183:39–45

    PubMed  Google Scholar 

  30. Percival SS, Harris ED (1989) Ascorbate enhances copper transport from ceruloplasmin into human K562 cells. J Nutr 119:779–784

    PubMed  Google Scholar 

  31. Percival SS, Harris ED (1990) Copper transport from ceruloplasmin: characterization of the cellular uptake mechanism. Am J Physiol 258:C140–146

    PubMed  Google Scholar 

  32. Rauch H, Dupuy D, Stockert RJ, Sternlieb I (1986) Hepatic copper and superoxide dismutase activity in toxic milk mutant mice. In: Rotilio G (ed) Superoxide and superoxide dismutase in chemistry. Elsevier, Amsterdam

    Google Scholar 

  33. Scheinberg IH, Stemblieb I (1984) Wilson's Disease. W.B. Saunders Philadelphia

    Google Scholar 

  34. Scheinberg IH, Sternlieb I, Schilsky M, Stockert RJ (1987) Penicillamine may detoxify copper in Wilson's disease. Lancet I:95

    Google Scholar 

  35. Smith AL, Danks DM (1978) Secondary copper accumulation with neurological damage in children with chronic liver disease. Br Med J 2:1400

    Google Scholar 

  36. Tanner MS, Portmann B (1981) Indian childhood cirrhosis. Arch Dis Child 56:4–6

    PubMed  Google Scholar 

  37. Tanner MS, Bhave SA, Kantarjian AH, Pandit AN (1983) Early introduction of copper-contaminated animal milk feeds as a possible cause of Indian childhood cirrhosis. Lancet II: 992–995

    Google Scholar 

  38. Tavassoli M, Kishimoto T, Kataoka M (1986) Liver endothelium mediates the hepatocyte's uptake of ceruloplasmin. J Cell Biol 102:1298–1303

    PubMed  Google Scholar 

  39. Underwood BJ (1977) Trace elements in human and animal nutrition, 4th edn. Academic, New York

    Google Scholar 

  40. Walker-Smith JA, Blomfield J (1973) Wilson's disease or chronic copper poisoning? Arch Dis Child 48:476–479

    PubMed  Google Scholar 

  41. Walshe JM (1986) Tetrathiomolybdate (MoS4) as an anticopper agent in man. In: Scheinberg IH, Walsh JM (eds) Orphan diseases/orphan drugs. Manchester University Press, Manchester

    Google Scholar 

  42. Walshe JM (1989) Wilson's disease patients can be decoppered. Lancet II:228

    Google Scholar 

  43. Walshe JM, Dixon AK (1986) Dangers of non-compliance in Wilson's disease. Lancet I:845–847

    Google Scholar 

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Authors and Affiliations

  1. Murdoch Institute, Royal Children's Hospital, 3052, Parkville, Victoria, Australia

    D. M. Danks

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Danks, D.M. Copper and liver disease. Eur J Pediatr 150, 142–148 (1991). https://doi.org/10.1007/BF01963553

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  • DOI: https://doi.org/10.1007/BF01963553

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