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Metal-Related Diseases of Genetic Origin

  1. Bibudhendra Sarkar

Published Online: 15 DEC 2011

DOI: 10.1002/9781119951438.eibc0250

Encyclopedia of Inorganic and Bioinorganic Chemistry

Encyclopedia of Inorganic and Bioinorganic Chemistry

How to Cite

Sarkar, B. 2011. Metal-Related Diseases of Genetic Origin. Encyclopedia of Inorganic and Bioinorganic Chemistry. .

Author Information

  1. University of Toronto, Toronto, ON, Canada

Publication History

  1. Published Online: 15 DEC 2011


In humans, there are several genetic disorders of metal metabolism. Wilson and Menkes diseases are genetic disorders of copper transport. The genes from these two diseases encode copper-transporting ATPases. Mutations in Wilson disease gene cause toxic accumulation of copper in the cells whereas mutations in Menkes disease gene cause copper deficiency and lack of its incorporation in important copper enzymes. Wilson disease is treated by chelating agents such as d-penicillamine and trientine and zinc, which inhibits absorption of copper from the intestine. Current treatment for Menkes disease is subcutaneous injection of copper-histidine. Hereditary hemochromatosis, thalassemia, and aceruloplasminemia are major disorders of iron metabolism. The gene responsible for hereditary hemochromatosis encodes a protein, which is very similar to major histocompatibility complex on chromosome 6, that has been proposed to down-regulate iron absorption. The disease is treated by weekly venesection of approximately 0.5 L of blood. Thalassemia causes severe iron accumulation as a result of disturbances in the synthesis of one or more of the globin chains of hemoglobin. The chelating agent used for the treatment is deferoxamine administered subcutaneously. The search for an orally administered iron chelator has been intensified in recent years leading to chemical trials of chelator such as deferiprone (L1). Aceruloplasminemia is caused by mutations in the ceruloplasmin gene resulting in iron accumulation in various tissues. Deferoxamine has been used to treat this disease. Acrodermatitis enteropathica is a genetic disorder of zinc metabolism. Mutations in the gene responsible for zinc transport result in insufficient absorption of zinc in this disease, which can be ameliorated by zinc supplementation. Several less common genetic disorders of metal metabolism are discussed briefly.


  • metal-associated genetic diseases;
  • copper-transporting atpases;
  • Wilson disease;
  • menkes disease;
  • hereditary hemochromatosis;
  • thalassemia;
  • aceruloplasminemia;
  • acrodermatitis enteropathica;
  • ceruloplasmin;
  • iron overload