Este artigo foi revisto pela última vez em
Este artigo foi modificado pela última vez em 10 de Julho de 2017.

What is it?

Wilson’s disease is an inherited condition associated with abnormal copper metabolism that results in excess storage of copper, primarily in the liver and brain. Copper is an essential mineral that is absorbed into the body through diet. It is incorporated into enzymes that play a role in the regulation of iron metabolism, formation of connective tissue, energy production at the cellular level, the production of melanin, and the function of the nervous system and brain. Copper is absorbed in the intestines, bound to a carrier protein, transported to the liver, and then stored or used – with the excess excreted into the bile and removed from the body in the stool. Normally, about 95% of the copper found in the blood is contained in ceruloplasmin. This enzyme, which plays a role in iron metabolism in the body, is formed in the liver.

Wilson’s disease is an autosomal recessive disorder - it takes two altered gene copies, one from each parent, to cause the disorder. Those with only one copy are carriers and can pass the mutation on to their children but do not have symptoms of the disease. The gene mutation in Wilson’s disease is at the ATP7B gene. This gene is needed both to attach copper to the developing ceruloplasmin molecule and to excrete copper into the bile, needed for elimination of excess copper from the body. An alteration in both gene copies leads to excess copper storage in the liver and to a decrease in ceruloplasmin in the blood. As the build-up becomes toxic, copper begins to damage the cells and tissues in the liver, spills into the blood, and begins to form deposits in other organs such as the brain and kidneys. Free (unbound) copper concentrations in the blood increase and can cause oxidative damage to cells. Affected patients may have signs and symptoms associated with the liver dysfunction, neurologic damage, or both. The severity of the condition depends partly upon the gene mutations present.

About 1 in 30,000 people in the United States have Wilson’s disease and as many as 1 in 90 are estimated to be carriers. There are currently about 40 known normal variants of the ATP7B gene and over 400 different mutations of the ATP7B gene that have been associated with Wilson’s disease. Only a few of these mutations are common, however, with their prevalence varying with ethnicity throughout the world. Affected patients may have two copies of the same genetic mutation or two different mutations.

Wilson’s disease patients with liver involvement typically have symptoms starting in early childhood; those with brain involvement may have neurologic and psychiatric symptoms beginning in their teens or early twenties, but the age range for both can vary from about three years old to more than fifty.

Deposits of copper in the liver can lead to acute, chronic, and progressive hepatitis and cirrhosis and cause signs and symptoms such as:

Patients with brain involvement may have a range of physical symptoms including:

  • dystonia
  • stiff face muscles
  • tremors
  • abnormal eye movements
  • altered gait
  • difficulty walking, speaking, and swallowing

They may also experience behavioral changes such as depression, paranoia, impulsiveness, obsessive behavior, aggression, and a shortened attention span.

About 50% of those with liver disease and 90% of those with brain involvement will have Kayser-Fleischer rings, deposits of copper in a ring around the cornea that can be seen with an eye exam called a slit lamp examination. Some patients may also experience anemia.

Left untreated, Wilson’s disease tends to become progressively worse and is eventually fatal. With early detection and treatment, most of those affected can live relatively normal lives. Liver and neurologic damage that occurs prior to treatment may improve, but it is often permanent.


The goals with testing are to diagnose Wilson’s disease, evaluate its severity, distinguish between those who have the disease and those who are carriers, rule out other causes of liver and neurological dysfunction, and to monitor the effectiveness of treatment for Wilson’s disease. Testing is also used to identify family members who are presymptomatic or carriers, and sometimes for prenatal evaluation.

Laboratory Tests
Biochemical testing – Care must be taken to avoid external copper contamination in sample collection. Repeat testing of abnormal results may be recommended. Test results of people who are carriers may overlap with those who have Wilson’s disease but are presymptomatic. Other diseases may also result in excess copper storage and increased copper in the blood. Acute cases of Wilson’s disease may be difficult to distinguish from other forms of hepatitis. Testing may include:

  • Ceruloplasmin – ordered to help diagnose Wilson’s disease; usually decreased but about 5% of affected patients who have neurological symptoms will have normal ceruloplasmin levels as will up to 40% of those with hepatic symptoms.
  • Total serum copper – may be ordered to help diagnose; usually decreased.
  • Free serum copper (non-ceruloplasmin-bound) – used to diagnose and monitor; usually increased.
  • 24-hour urine copper – used to diagnose and monitor; usually increased.
  • Hepatic copper – a liver tissue biopsy collected to help diagnose; deposits of copper may not be evenly distributed in the liver.

Molecular genetic testing – This is specialized testing that is available from a limited number of reference or research laboratories. It is used to diagnose Wilson’s disease and identify mutation(s) and identify carriers. Some prediction of disease severity can be established based upon the mutations present, but testing cannot determine the severity, complications, or organ involvement that will be experienced by a specific individual. Severity can vary significantly, even between family members with the same mutations.

  • ATP7B gene
  • - Panels of the most prevalent mutations in a region or ethnic population may be performed.
    - If the mutations have been identified in a Wilson’s disease patient, then the family members of the patient can be tested for those specific mutations.
    - Gene sequencing can be performed to examine the entire gene for mutations. This is the most thorough test.
    • Linkage analysis – This requires blood from parents, siblings, and an affected family member. It compares genetic information present close to the ATP7B gene.

    Other tests may be performed to evaluate organ function and blood cell status, including:

    Non-Laboratory Tests

    • Eye exam – slit lamp for Kayser-Fleischer rings in the cornea
    • Clinical examination and personal and family history
    • Magnetic resonance imaging (MRI) scan
    • Computerized tomography (CT) scan


    There is no way to prevent or cure Wilson’s disease, but it can be successfully managed. Symptoms, complications, and response to treatment will vary from person to person, even within families who have the same genetic mutations.

    In patients with symptomatic Wilson’s disease, the goals of treatment are to decrease excess copper stores, prevent their recurrence, preserve liver, neurological, and kidney function, and to minimize complications associated with the condition and associated with the medications used to treat it.

    Patients who are asymptomatic but have been diagnosed as having Wilson’s disease, such as siblings of affected patients, will usually be treated to decrease any excess copper that is present and to prevent its buildup. Those who are carriers of Wilson’s disease should receive genetic counseling but do not usually require any treatment.

    Affected patients are put on a low copper diet. Most are treated first with one of two chelating agents, D-penicillamine or trientine (triethylene tetramine dihydochloride), to increase urinary excretion of copper and decrease copper stores. Patients must be monitored for side effects as the medications can decrease red and white blood cells and platelets and can cause nausea, fever, and skin conditions. Some patients must take these medications long-term; others can switch to zinc therapy once copper stores have normalized. High doses of zinc inhibit the absorption of copper.

    Copper dietary restriction and treatment must be continued throughout a patient’s life. Treatments may be changed but should never be discontinued. Untreated Wilson’s disease is eventually fatal, and organ damage is usually permanent. In some severe cases, liver transplantation may be necessary.

    Antioxidants such as vitamin E may be recommended to help prevent liver and other tissue damage.

    Related Pages

    On This Site
    Tests: Ceruloplasmin, Copper
    Conditions: Liver disease
    Features: The Universe of Genetic Testing

    Elsewhere On The Web
    Wilson’s Disease Association

    Article Sources

    NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

    Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Garganta, C. Chapter 37, Inborn Errors of Metabolism. Pp. 425-440.

    Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp. 231, 233, 293, 1099, 1169.

    McMilln, G. and Roberts, W. (2007 July, Reviewed). Wilson Disease. ARUP Consult [On-line information]. Available online at through Accessed on 7/17/07.

    (2003 March). Wilson’s Disease. NDDIC [On-line information]. Available online at through Accessed on 7/17/07.

    Cox, D. and Roberts, E. (2006 January 24). Wilson Disease. GeneReviews [On-line information]. Available online through Accessed on 7/17/07.

    Kirmse, B. (2006 August 11). Wilson's disease. MedlinePlus Medical Encyclopedia [On-line information]. Available online at Accessed on 7/21/07.

    The Wilson’s Disease Association International. About Wilson’s Disease [On-line information]. Available online at through Accessed on 7/21/07.

    Guide to Wilson’s Disease. EuroWilson [On-line information]. Available online at through Accessed on 7/21/07.

    Copper. Merck Manual of Medical Information – Second Home Edition [On-line information]. Available online at through Accessed on 7/17/07.

    (© 2006-2007). Wilson Disease Testing. ARUP Consult Testing Algorithms [On-line information]. PDF available for download at through Accessed on 7/17/07.

    Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition]. Pp. 2113-2114.

    Das, S. and Ray, K. (2006 October 13). Wilson’s Disease: An Update. Medscape from Nature Clinical Practice Neurology [On-line information]. Available online at through Accessed on 7/27/07.

    Ferenci, P. (2004 January 28). Diagnosis and Current Therapy of Wilson's Disease. Medscape from Aliment Pharmacol Ther 19(2):157-165, 2004. [On-line information]. Available online at through Accessed on 9/24/07.