Pathophysiology and clinical features of Wilson disease

Metab Brain Dis. 2004 Dec;19(3-4):229-39. doi: 10.1023/b:mebr.0000043973.10494.85.

Abstract

Wilson disease is an autosomal recessive inherited disorder of copper metabolism resulting in pathological accumulation of copper in many organs and tissues. ATP7B is the gene product of the Wilson disease 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. Mutations of the gene result in impaired trafficking of copper in and through the hepatocytes. More than 200 mutations of Wilson disease gene were found, the most common ones being H1069Q (in Europe) and R778L (in Asia). Wilson disease may present under a variety of clinical conditions, commonly as liver and/or neuropsychiatric disease. The pathogenesis of hepatic and neurologic Wilson disease is a direct consequence of copper accumulation. Presence of copper causes oxidative stress resulting in cell destruction. The diagnosis of Wilson disease requires a combination of a variety of clinical symptoms, biochemical tests, and detection of gene mutations, which are the basis of a score proposed by a group of international experts. Initial treatment for symptomatic patients should include a chelating agent (penicillamine or trientine). Treatment of presymptomatic patients or maintenance therapy can also be accomplished with zinc.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Brain / metabolism
  • Brain / physiopathology
  • Cation Transport Proteins / genetics*
  • Chelating Agents / therapeutic use
  • Copper / metabolism*
  • Copper-Transporting ATPases
  • Hepatolenticular Degeneration / genetics*
  • Hepatolenticular Degeneration / physiopathology*
  • Hepatolenticular Degeneration / therapy
  • Humans
  • Liver / metabolism
  • Liver / physiopathology
  • Mutation / genetics*
  • Oxidative Stress / genetics
  • Zinc / therapeutic use

Substances

  • Cation Transport Proteins
  • Chelating Agents
  • Copper
  • Adenosine Triphosphatases
  • ATP7B protein, human
  • Copper-Transporting ATPases
  • Zinc