- Also Known As:
- Copper Storage Disease
- Hepatolenticular Degeneration
- Inherited Copper Toxicity
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What is Wilson disease?
Wilson disease is a rare inherited disorder 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 the 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…
Wilson disease is a rare inherited disorder 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 the 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, and transported to the liver. The liver stores some of the copper and binds most of the rest to a protein called apoceruloplasmin to produce the enzyme ceruloplasmin. About 95% of the copper in the blood is bound to ceruloplasmin, and most of the rest is bound to other proteins, such as albumin. Only a small amount is normally present in the blood in a free (unbound) state. Excess copper is normally released into the bile and removed from the body in the stool. Some copper is also eliminated by the kidneys into the urine.
Wilson disease is an autosomal recessive disorder, which means it takes two copies of a disease-causing (pathogenic) variant, one inherited from each parent, to cause the disorder. If you have only one copy of a pathogenic variant, you are a carrier and can pass the genetic variant on to your children but you do not have symptoms of the disease.
The genetic variant in Wilson disease is located at the ATP7B gene. This gene is needed both to attach copper to the developing ceruloplasmin molecule and to release copper into the bile. A variant in both gene copies (homozygous) 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. You may have signs and symptoms associated with liver dysfunction, nervous system damage, or both. The severity of the condition depends partly upon the genetic variants present but will also vary from person to person.
About 1 in 30,000 people in the United States have Wilson disease and as many as 1 in 90 are estimated to be carriers of a pathogenic variant. There are currently about 40 known normal variants of the ATP7B gene and over 260 different pathogenic variants of the ATP7B gene that have been associated with Wilson disease. Only a few of these genetic variants are common, however, with their prevalence varying with ethnicity throughout the world. Those affected may have two copies of the same genetic variant or two different variants.
About Wilson Disease
Signs and Symptoms
Signs and symptoms of Wilson disease that affect the liver typically start to develop in early childhood. If Wilson disease affects the brain, you may have nervous system and psychiatric symptoms beginning in your teens or early twenties. However, the age range for developing symptoms can vary widely, from age 3 years old to older than age 50.
- Yellowing of the skin and whites of the eyes (jaundice)
- Abdominal pain
- Lack of appetite
- Fluid buildup in the abdomen (ascites)
If your brain is affected, you may have a range of physical symptoms, including:
- Muscle contractions that persist and cause limb twitching and repetitive movements (dystonia)
- Stiff face muscles
- Abnormal eye movements
- Altered gait
- Difficulty walking, speaking, and swallowing
You may also experience behavioral changes such as depression, paranoia, impulsiveness, obsessive behavior, aggression, and a shortened attention span.
About 50% of people with liver disease and 90% of people whose brain is affected will have Kayser-Fleischer rings. These are deposits of copper in a ring around the cornea that can be seen with an eye exam called a slit lamp examination.
Left untreated, Wilson 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 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 monitor the effectiveness of treatment for Wilson disease. Testing is also used to identify family members who have the disease but no symptoms yet or are carriers, and sometimes for prenatal evaluation.
Laboratory tests used for evaluating an individual for Wilson disease are listed below. Repeat testing of abnormal results may be recommended. Test results of people who are carriers may overlap with people who have Wilson disease but haven’t developed symptoms yet. Other diseases may also result in excess copper storage and increased copper in the blood. Acute cases of Wilson disease may be difficult to distinguish from other forms of hepatitis.
The following tests may be used to diagnose and/or monitor treatment:
- Ceruloplasmin – the result is usually decreased with Wilson disease, but about 5% of those affected who have nervous system symptoms will have normal ceruloplasmin levels as will up to 40% of those with liver symptoms.
- Total serum copper – the result is usually decreased with Wilson disease.
- Free serum copper (non-ceruloplasmin-bound) – usually increased
- 24-hour urine copper – usually increased
- Liver (hepatic) copper – a sample of liver tissue (biopsy) may be collected to help diagnose the disease. However, deposits of copper may not be evenly distributed in the liver.
The following table summarizes some results that may be seen:
|Test||Result Seen in Wilson Disease|
|Total copper, blood||Low but may be normal|
|Free copper, serum||High|
|Ceruloplasmin||Low but may be normal. About 5% of people with nervous system symptoms will have normal ceruloplasmin levels as will up to 40% of those with liver symptoms.|
|Copper, urine||Very high|
|Copper, liver/hepatic||Positive but, depending on the site sampled, may be negative. Excess copper in the liver is often unevenly distributed and may not be detected in a sample.|
Molecular genetic testing – this testing is used to diagnose Wilson disease, identify the genetic variants present, and identify carriers. Sometimes the severity of the disease can be predicted based upon the variants present, but genetic testing cannot determine specifically for you how severe the disease will be, what complications you will develop, or which organs will be affected. Disease severity can vary significantly, even between family members with the same variants.
- ATP7B gene: panels of the most common variants in a region or ethnic population may be performed.
- If the genetic variants have been identified in a person with Wilson disease, then the family members of that person can be tested for those specific variants.
- Gene sequencing can be performed to examine the entire gene for variants. This is the most thorough test.
- Linkage analysis: this requires blood from parents, siblings, and an affected family member. It compares genetic information that is located close to the ATP7B gene.
Other general tests may be performed to evaluate organ function and blood cells, including:
Your healthcare practitioner may perform or order one or more of the following:
- Eye exam (slit lamp for Kayser-Fleischer rings in the cornea)
- Clinical examination and personal and family history
- Magnetic resonance imaging (MRI) scan of your brain
- Computerized tomography (CT) scan of your brain
There is no way to prevent or cure Wilson 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 variants.
If you have signs and symptoms of Wilson disease, the goals of treatment are to decrease excess copper stores and prevent them from building up again. Treatment also aims to preserve liver, nervous system, and kidney function and to minimize complications from the condition and the medications used to treat it.
If you do not have symptoms but have been diagnosed as having Wilson disease through genetic testing, you will usually be treated to decrease any excess copper that is present and to prevent its buildup. If you are identified as a carrier of Wilson disease, you should receive genetic counseling but you likely do not require any treatment.
Most people with Wilson disease are treated first with one of two chelating agents, D-penicillamine or trientine (triethylene tetramine dihydochloride), to help the body get rid of excess copper in the urine and to decrease copper stores. You 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 people must take these medications long-term. Others can switch to zinc therapy once copper stores have returned to normal. High doses of zinc help prevent your body from absorbing copper.
You will be put on a low copper diet. Copper dietary restrictions and treatment must be continued throughout your life. Treatments may be changed but should never be discontinued. Untreated Wilson 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.
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