What is Wilson’s Disease?
Wilson’s Disease, also known as hepatolenticular degeneration, is a rare, genetic disorder that results in the accumulation of copper in several vital organs such as the liver, eyes, and brain as well as increased levels of copper in the blood stream. (Wilson 1912) (Bearn 1953) Over time this accumulation of copper can cause neurological damage and, if left untreated, death. (Wilson 1912) However, if properly diagnosed and treated, the disease progression can be stopped and existing symptoms may even improve. One in every 30,000 people will develop Wilson’s Disease in their lifetime and likely begin to display symptoms between the ages of 5 and 35 (Rosencrantz and Schilsky 2011).
Many biological processes in humans require copper which is obtained from diet. (Turnlund 1998) However, excess copper accumulation in the body is poisonous. In healthy individuals the transmembrane protein ATP7B works in the liver where it pairs copper with another protein called ceruloplasmin that can carry the copper through the blood stream to other tissues where it can be used for other metabolic processes. When there is excess copper in the liver, ATP7B can repackage it and send it to the bile. (Turnlund 1998) Then, the bile is secreted into the digestive tract and the copper is excreted from the body in feces. (Turnlund 1998) However, individuals with Wilson’s Disease have inherited a mutation in the gene that codes for the transmembrane protein ATP7B which is responsible for transporting copper out of liver cells (Gourdon et al. 2012). This mutation is inherited in an autosomal recessive pattern and impairs ATP7B such that it is unable to excrete copper from the liver cells, thus causing toxic copper accumulation (Gourdon et al. 2012). Some ATP7B proteins can also be found in the brain and kidneys.
Wilson’s Disease presents with a wide range of symptoms caused by toxic accumulation of copper in the body. These symptoms can present in the liver, brain, central nervous system, kidney, and eyes. There are also some psychiatric symptoms associated with Wilson’s Disease. Perhaps the most characteristic symptom of Wilson’s Disease are the Kayser-Fleisher Rings: brown colored rings around the irises of the eyes resulting from excess copper accumulation in the eyes. Accumulation of copper in the liver causes a variety of liver symptoms including cirrhosis, acute hepatitis, nonalcoholic fatty liver, hepatomegaly, and acute liver failure. Neurological symptoms include migraines, insomnia, seizures, drooling, and movement disorders such as muscle tremors. Psychiatric symptoms include personality changes, psychosis, neurotic behaviors, and depression (WDA 2009).
There are several treatment options for Wilson’s Disease that can halt disease progression and treat existing symptoms. Chelating agents, molecules that bind to copper and facilitate its excretion through urine, are one of the most popular therapies (Rosencrantz and Schilsky 2011). Treatment with zinc is also effective and has gained popularity over the years. Zinc therapy is focused at maintaining a normal level of copper in the blood stream to prevent copper poisoning. (Hoogenraad 2006). Chelating agents and zinc therapy are lifelong treatments that manage Wilson’s Disease very well and offer patients the opportunity to live a fairly symptom free life. However, there is currently a debate in the scientific community and among patients as to which treatment–chelating agents or Zinc therapy–provides the best results with the fewest side affects. There is also new research into cell therapy that would replace diseased liver cells with healthy ones may provide a cure in the future. As of now, the only short term cure for Wilson’s Disease is a liver transplant which is only an option for patients with advanced liver damage (Rosencrantz and Schilsky 2011). There are currently no widely available therapies to provide a lifelong cure for Wilson’s Disease (Gupta 2014).
Other Resources on Wilson’s Disease:
Bearn AG. (1953) Genetic and biochemical aspects of Wilson’s disease. Am J Med.15, 442–449. DOI:10.1016/0002-9343(53)90134-X
Gourdon, P., Sitsel, O., Karlsen, J. L., Møller, L. B., and Nissen, P. (2012) Structural models of the human copper P-type ATPases ATP7A and ATP7B. Biological Chemistry. 393, 205–216. DOI: 10.1515/hsz-2011-0249
Gupta, S. (2014) Cell therapy to remove excess copper in Wilson’s disease. Ann. N.Y. Acad. Sci. 1315, 70–80. DOI: 10.1111/nyas.12450
Hoogenraad, T. U. (2006) Paradigm shift in treatment of Wilson’s disease: zinc therapy now treatment of choice. Brain Dev. 28, 141–146. DOI: 10.1016/j.braindev.2005.08.008
Rosencrantz, R., and Schilsky, M. (2011) Wilson Disease: Pathogenesis and Clinical Considerations in Diagnosis and Treatment. Seminars in Liver Disease. 31, 245–259. DOI: 10.1055/s-0031-1286056
Turnlund, J. (1998) Human Whole-Body Copper Metabolism. J. Clin. Nutr. 67, 960S-964S. PMID: 9587136
Wilson, S. a. K. (1912) Progressive Lenticular Degeneration: A Familial Nervous Disease Associated with Cirrhosis of the Liver. Brain. 34, 295–507. DOI:http://dx.doi.org/10.1093/brain/34.4.295
Wilson (Wilson’s) Disease Symptoms [online] http://www.wilsonsdisease.org/wilson-disease/wilsondisease-symptoms.php (Accessed April 1, 2015).
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