Wilson disease (WD) is a rare inherited disorder that causes excess copper to accumulate in the body. It is also known as hepatolenticular degeneration. Steadily increasing amounts of copper circulating in the blood are deposited primarily in the brain, liver, kidneys, and the cornea of the eyes. WD is fatal if it is not recognized and treated. It is named for a U.S. neurologist, Samuel A. K. Wilson, who first described it in 1912.
Under normal conditions, copper that finds its way into the body through the diet is processed within the liver. This processed form of copper is then passed into the gallbladder, along with the other components of bile (a fluid produced by the liver, which enters the small intestine in order to help in digestive processes). When the gallbladder empties its contents into the first part of the small intestine (duodenum), the copper in the bile enters and passes through the intestine with the waste products of digestion. In healthy individuals, copper is then passed out of the body in stool.
In Wilson disease, copper does not pass from the liver into the bile, but rather begins to accumulate within the liver. As copper levels rise in the liver, the damaged organ begins to allow copper to flow into the bloodstream, where it circulates. Copper is then deposited throughout the body, building up primarily in the kidneys, the brain and nervous system, and the eyes. Wilson disease, then, is a disorder of copper poisoning occurring from birth.
Wilson disease affects approximately 1 in 30,000 to 1 in 100,000 individuals and can affect people from many different populations. Approximately 1 in 90 individuals are carriers of the gene for Wilson disease.
Wilson disease is inherited in an autosomal recessive manner. Autosomal recessive refers to the pattern of inheritance where each parent carries a gene for the disease on one of his or her chromosome pairs. When each parent passes on the chromosome with the gene for Wilson disease, the child will be affected with the disease. Both males and females can be affected with Wilson disease. If an individual is a carrier of the Wilson disease gene they do not have any symptoms of this disease. In order to be affected, an individual must inherit two copies of the gene, one from each parent. Many cases of Wilson disease may not be inherited but occur as a spontaneous mutation in the gene.
The gene for Wilson disease is located on chromosome number 13. The name of the gene is called ATP7B and is thought to be involved in transporting copper. More than 200 different mutations of this gene have been identified, making diagnosis by genetic testing difficult.
Neurological symptoms are the first to occur in half of all patients due to copper accumulation in the brain and nervous system. The average age of onset for neurological symptoms is 21. These symptoms include tremors of the hands, uncontrollable movements of the limbs, stiffness, drooling, difficulty swallowing, difficulty talking, and headache. There is no change in patient's intelligence.
About one-third of all patients with Wilson disease have a variety of psychiatric symptoms as the first signs of the disease. These symptoms include inability to cope, depression, irritability, increased anger, and inappropriate behavior. Often times patients have trouble completing tasks at work or in school.
Other symptoms that can affect patients with Wilson disease, and may occur before or after a diagnosis has been made, include joint disorders, symptoms of arthritis, and skeletal problems such as osteoporosis. Patients have occasionally been affected by kidney stones and abnormal handling of glucose in their body, and women may have menstrual cycle irregularities including stopping their regular cycle temporarily.
An easy way to diagnose Wilson disease is to measure the amount of a glycoprotein found in the blood called ceruloplasmin. Low levels of ceruloplasmin can diagnose the disease in about 80% of affected patients. This procedure is not as effective for women taking birth control pills, pregnant women, or infants younger than six months of age.
A second test involving an eye examination to detect a characteristic ring of copper deposited in a membrane of the cornea (referred to as Kayser-Fleischer rings) is very easy to perform and is very useful in diagnosing patients who have already exhibited symptoms. This test is not as effective in people without symptoms. This diagnostic test cannot be used by itself to make a diagnosis because some patients with liver disease but not Wilson disease will test positive.
A third test for diagnosing Wilson disease involves measuring the amount of copper in the liver. This can be accomplished by sampling a portion of the liver, called a biopsy. This is one of the most effective ways in which to diagnose Wilson disease, but the procedure itself is more difficult to perform than the others.
Other tests are also useful, for example measuring the amount of copper passed into the urine daily (high in Wilson disease). Another lab test measures the ability of a patient's ceruloplasmin to bind with a form of copper (decreased in Wilson disease). Finally, as discussed under genetic profile, some patients can be diagnosed through a DNA test to determine whether or not they carry two genes for Wilson disease. This test does not always prove to be useful in certain patients and is of most use when used to test the brothers and sisters of affected patients.
Molecular genetic testing is not particularly valuable in diagnosing WD because of the large number of possible gene mutations.
Treatment involves lifelong administration of either D-penicillamine (Cuprimine, Depen) or trientine hydrochloride (Syprine). Both of these drugs remove copper deposits throughout the body by binding to the copper, which then leaves the body in the urine. This type of treatment is called chelation therapy. Zinc acetate (Galzin) and a low-copper diet are other ways used to treat Wilson disease.
Penicillamine has a number of serious side effects, including:
Careful monitoring is necessary. When patients have side effects from penicillamine, the dose can sometimes be lowered to an effective level that causes fewer difficulties. Alternatively, steroid medications may be required to reduce certain sensitivity reactions. Trientine has fewer potential side effects, but must still be carefully monitored.
Treatment with zinc acetate is also an effective way to remove excess copper from the body. Zinc is a metal that works to block copper absorption and bind copper in the intestinal cells until it is all released into the stool approximately one week later. The benefit of treatment with zinc is there are no toxic side effects; however, the zinc is a slower-acting agent than the other drugs. It takes four to eight months for the zinc to be effective in reducing the overall amount of copper in the body.
Finally, patients with Wilson disease are encouraged to follow a diet low in copper, with an average copper intake of 1.0 mg per day. Foods to be avoided for the high levels of copper include liver and shellfish. Patients are also instructed to monitor their drinking water for excess levels of copper and drink distilled water instead.
Without treatment, Wilson disease is always fatal. With treatment, symptoms may continue to worsen for the first six to eight weeks. After this time, definite improvement should begin to be seen. However, it may take several years (two to five) of treatment to reach maximal benefit to the brain and liver. Even then, many patients are not returned to their original level of functioning. Patients with Wilson disease need to maintain some sort of anticopper treatment for the rest of their lives in order to prevent copper levels from rising in the body. Interruptions in treatment can result in a relapse of the disease, which is not reversible and can ultimately lead to death.
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Velez-Pardo, C., et al. “New Mutation (T1232P) of the ATP-7B Gene Associated with Neurologic and Neuropsychiatric Dominance Onset of Wilson's Disease in Three Unrelated Colombian Kindred.” Neuroscience Letters 367, no. 3 (September 9, 2004): 360–64.
MedlinePlus. “Wilson Disease.” U.S. National Library of Medicine, National Institutes of Health. https://medlineplus.gov/wilsondisease.html (accessed April 23, 2018).
American Liver Foundation, 39 Broadway, Ste. 2700, New York, NY, 10006, (212) 668-1000, Fax: (212) 483-8179, http://www.liverfoundation.org .
National Organization for Rare Disorders, PO Box 8923, New Fairfield, CT, 06812-8923, (800) 999-6673, http://www.rarediseases.org .
Wilson Disease Association, 5572 N. Diversey Blvd, Milwaukee, WI, 53217, (414) 961-0533, (866) 961-0533, firstname.lastname@example.org, http://www.wilsonsdisease.org .
Katherine S. Hunt, MS
Rebecca J. Frey, PhD