Gastroenterology

Gastroenterology

Volume 125, Issue 6, December 2003, Pages 1868-1877
Gastroenterology

Special report and review
Wilson disease

https://doi.org/10.1053/j.gastro.2003.05.010Get rights and content

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Physiology

Copper is an essential trace element that permits the facile transfer of electrons in a diverse, yet essential, group of cuproenzymes required for cellular respiration, iron oxidation, pigment formation, neurotransmitter biosynthesis, antioxidant defense, peptide amidation, and connective tissue formation.12 Numerous dietary foods are rich in copper that is absorbed primarily through the stomach and duodenum. Biliary excretion is the only physiological route for copper elimination, and each day

Genetics

Wilson disease is observed with a prevalence of approximately 1:30,000, and this is equivalent among all ethnic groups. Although the gene frequency is increased in specific consanguineous populations in which haplotype studies provide evidence for a founder effect, worldwide the heterozygous carrier rate is approximately 1:100, with a disease incidence of 15–25 per million.44, 45 Molecular analysis of the ATP7b gene in affected patients and families has detected more than 200 distinct

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      Citation Excerpt :

      Copper is incorporated into ceruloplasmin, the main Cu-binding protein in blood serum (Prohaska and Gybina, 2004), with the help of Cu-transporting adenosinetriphosphatase (ATP7B), which also facilitates its removal from the liver through secretion into bile to be stored in the gall bladder and excreted via feces (La Fontaine et al., 2010). Wilson's disease patients have a mutation in the ATP7B gene, which encodes the ATP7B protein, and (1) causes ceruloplasmin to be secreted in a form that lacks Cu and quickly breaks down in the bloodstream, and (2) disrupts the excretion of liver Cu in bile (Gitlin, 2003). Together, these result in the gradual accumulation of Cu in the liver, and lead to hepatocyte dysfunction, cell death, and the eventual release of Cu into the bloodstream and accumulation in other parts of the body (Bull et al., 1993; Gitlin, 2003; Tanzi et al., 1993).

    View all citing articles on Scopus

    Supported by National Institutes of Health Grants DK61763, DK44464, HL41536, and HD39952.

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