Wilson disease is a rare inherited disorder that prevents your body from getting rid of extra copper. You need a small amount of copper from food to stay healthy. Too much copper is poisonous.

Normally, your liver releases extra copper into bile, a digestive fluid. With Wilson disease, the copper builds up in your liver, and it releases the copper directly into your bloodstream. This can cause damage to your brain, kidneys, and eyes.

Wilson disease is present at birth, but symptoms usually start between ages 5 and 35. It first attacks the liver, the central nervous system or both. The most characteristic sign is a rusty brown ring around the cornea of the eye. A physical exam and laboratory tests can diagnose it.

Treatment is with drugs to remove the extra copper from your body. You need to take medicine and follow a low-copper diet for the rest of your life. Don't eat shellfish or liver, as these foods may contain high levels of copper. At the beginning of treatment, you'll also need to avoid chocolate, mushrooms, and nuts. Have your drinking water checked for copper content and don't take multivitamins that contain copper.

With early detection and proper treatment, you can enjoy good health.

Wilson disease is a genetic disorder that prevents the body from removing extra copper, causing copper to build up in the liver, brain, eyes, and other organs.

Your body needs a small amount of copper from food to stay healthy, but too much copper is harmful. Without treatment, Wilson disease can lead to high copper levels that cause life-threatening organ damage.

Experts are still studying how common Wilson disease is. Older studies suggested that about 1 in 30,000 people have Wilson disease. These studies were conducted before researchers discovered the gene mutations that cause Wilson disease.

Newer studies of people’s genes suggest that Wilson disease may be more common. A study in the United Kingdom found that about 1 in 7,000 people have gene mutations that cause Wilson disease.

Experts aren’t sure why gene studies suggest that Wilson disease is more common than previously thought. One reason might be that some people with Wilson disease are not diagnosed. Another reason might be that some people have gene mutations for Wilson disease but don’t develop the disease.

Wilson disease is a rare genetic condition that causes a person's body to store too much of the mineral copper. Over time, the extra copper can lead to organ damage that may cause death.

What is Wilson disease?

Wilson disease is a rare genetic condition that affects about one in 30,000 people. Wilson disease causes a person's body to store too much of the mineral copper. Many foods contain copper, and it is important for people to have a small amount of copper in the body. However, high levels of copper can damage organs in the body.

In Wilson disease, copper builds up in the liver, brain, eyes and other organs. Over time, the extra copper can lead to organ damage that may cause death.

Other names for Wilson disease include copper storage disease, hepatolenticular degeneration syndrome, WD and Wilson's disease.

What are the symptoms of Wilson disease?

Wilson disease may affect several of the body's systems.

Either the liver or the brain can be harmed first, with signs as early as 4 years, or as late as 70 years of age. Symptoms of liver disease include:

• Jaundice, which is when the skin or the white part of the eye turns yellow

• Fatigue

• Loss of appetite

• Swelling in the abdomen

• Easy bruising

Nervous system or mental health problems can develop in children or young adults who have Wilson disease. These problems include:

• Clumsiness

• Trembling

• Difficulty walking

• Problems with speech

• Problems with school work

• Depression

• Anxiety

• Mood swings

Eye changes and vision problems may also occur. These include:

• Kayser-Fleischer rings, which are green-to-brownish rings around the iris of the eye

• Difficulties with eye movement, particularly in looking upwards

In addition, people who have Wilson disease may experience:

• A low level of red blood cells, which is called anemia

• Low levels of white blood cells

• Low levels of clotting factors called platelets

• Slow clotting of blood

• High levels of protein, amino acids and uric acid in the urine

• Early onset of arthritis and bone loss

How is Wilson disease diagnosed?

Doctors diagnose Wilson disease through a physical exam and laboratory tests. The physical examination focuses on signs of liver disease as well as neurologic function.

The exam includes the use of a special light, called a slit lamp, to look for Kayser-Fleischer rings in a person's eyes. Kayser-Fleischer rings are found in almost all people with Wilson disease who show signs of neurologic damage. They are found in about half of people who have only signs of liver damage. Kayser-Fleischer rings do not harm a person's vision.

Doctors also order lab tests to measure the amount of copper in the blood and urine. Most people with Wilson disease will have lower-than-normal levels of copper in the blood, as well as lower blood levels of a protein called ceruloplasmin, a protein which contains copper. However, in people with acute liver failure caused by Wilson disease, copper levels in the blood are often higher than normal. Urine is collected over a 24 hour period to look for increased copper levels typical of Wilson disease.

In addition, a special procedure called a liver biopsy using a needle is done to remove a small piece of a person's liver. The liver sample is then examined under a microscope to look for damage found in Wilson disease. Copper content of the liver is also measured.

Genetic testing is frequently used to help diagnose Wilson disease in some people and is important for reliable early diagnosis of brothers and sisters of a patient with Wilson disease.

How is Wilson disease treated?

When Wilson disease is diagnosed early and treated effectively, people with the condition usually can have good health.

However, for patients who have severe cirrhosis, acute liver failure or other serious liver disorders, a liver transplant may be the only option for treatment.

People who have Wilson disease must be treated throughout their lives to lower and control the amount of copper in their bodies. When Wilson disease is diagnosed early and treated effectively, people with the condition usually can enjoy good health.

The first steps in treatment of Wilson disease involve:

• Removing the excess copper from the body.

• Reducing intake of foods that are rich in copper.

• Treating any liver or central nervous system damage.

Doctors currently use two drugs to treat Wilson disease: D-penicillamine (Cuprimine) and trientine (Syprine). These drugs help remove copper from organs and release it into the bloodstream. Once the copper enters the bloodstream, it is filtered out by the kidneys and excreted in urine.

Both drugs carry the possibility of major side effects. The drugs can worsen neurologic symptoms because the copper released into the bloodstream may sometimes be taken back up by the central nervous system. In addition, about one-quarter to one-third of people treated with D-penicillamine will experience other reactions to the medication, such as fever, rash and effects on the kidneys and bone marrow. The risks associated with trientine appear to be lower.

If they are pregnant, women with Wilson disease are given lower doses of these drugs to reduce the risk of having a baby with birth defects. Lower doses also improve the body's ability to heal if surgery is done during childbirth.

Zinc is another therapy for Wilson disease. Given in the form of zinc salts, such as zinc acetate (Galzin), it keeps the digestive tract from absorbing copper. Because zinc removes copper rather slowly, it usually is given as maintenance therapy for Wilson disease. It appears safe to use a full dose of zinc during pregnancy.

Once the symptoms of Wilson disease have improved and tests show that a person's copper levels have been lowered to a safe level, maintenance treatment begins. This can be with D-penicillamine or trientine or zinc. Blood and urine are routinely tested to make sure that copper remains at a safe level.

Doctors often recommend that people with Wilson disease reduce the amount of copper in their diets. Specifically, they are instructed to avoid liver or shellfish, which may contain high levels of copper. During initial treatment, patients may also be told not to eat other copper-rich foods, such as mushrooms, nuts, and chocolate. Once people begin maintenance treatment, they may be able to eat these foods in moderation. In addition, people with Wilson disease should avoid multivitamins that contain copper and have their drinking water checked for copper content.

Is Wilson disease inherited?

Yes. Wilson disease is inherited in what doctors call an autosomal (not on the X chromosome) recessive pattern. In this pattern of inheritance, a person needs to inherit two altered (mutated) copies of a gene - one from each parent - to develop the disease. The parents of a person with Wilson disease each carry one mutated copy of the gene and one normal copy of the gene, so they do not show signs or symptoms of the disease. Doctors refer to such people as "carriers."

With each pregnancy, couples who are carriers of the gene for Wilson disease face a 25 percent chance of having a child who will develop Wilson disease. Such a couple also has a 50 percent chance of having a child who is a carrier for Wilson disease and a 25 percent chance of having an unaffected child with two normal copies of the gene.

People have a higher chance of having Wilson disease if they have a family history of Wilson disease, especially if a first-degree relative—a parent, sibling, or child—has the disease.

People who have Wilson disease typically develop symptoms when they are between ages 5 and 40. However, some people develop symptoms at younger or older ages. Doctors have found the first symptoms of Wilson disease in infants as young as 9 months and in adults older than 70 years.

Mutations of a gene called ATP7B cause Wilson disease. These gene mutations prevent the body from removing extra copper. Normally, the liver releases extra copper into bile. Bile carries the copper, along with other toxins and waste products, out of the body through the digestive tract. In Wilson disease, the liver releases less copper into bile, and extra copper stays in the body.

The ATP7B mutations that cause Wilson disease are inherited, meaning they are passed from parent to child. These mutations are autosomal recessive, meaning that a person must inherit two ATP7B genes with mutations, one from each parent, to have Wilson disease. People who have one ATP7B gene without a mutation and one ATP7B gene with a mutation do not have Wilson disease, but they are carriers of the disease.

People can inherent Wilson disease if both parents are carriers who don’t have the disease. The chart below shows the chance of inheriting Wilson disease from parents who are carriers.

Normal Function

The ATP7B gene provides instructions for making a protein called copper-transporting ATPase 2. This protein is part of the P-type ATPase family, a group of proteins that transport metals into and out of cells by using energy stored in the molecule adenosine triphosphate (ATP). Copper-transporting ATPase 2 is found primarily in the liver, with smaller amounts in the kidneys and brain. It plays a role in the transport of copper from the liver to other parts of the body. Copper is an important part of certain enzymes that maintain normal cell functions. Copper-transporting ATPase 2 is also important for the removal of excess copper from the body.

Within liver cells, copper-transporting ATPase 2 is found in a structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. Here, copper-transporting ATPase 2 supplies copper to a protein called ceruloplasmin, which transports copper to other parts of the body via the blood. If copper levels in the liver get too high, copper-transporting ATPase 2 leaves the Golgi and transfers copper to small sacs (vesicles) for elimination through bile. Bile is a substance produced by the liver that is important for digestion and the removal of waste products.

Health Conditions Related to Genetic Changes

Wilson disease

Researchers have identified more than 250 ATP7B gene mutations that cause Wilson disease. About half the mutations change one of the protein building blocks (amino acids) used to make copper-transporting ATPase 2. This type of mutation alters the 3-dimensional structure of the protein or its stability, preventing copper-transporting ATPase 2 from functioning properly. A common amino acid substitution replaces the amino acid histidine with the amino acid glutamine at position 1069 in the protein (written as His1069Gln or H1069Q). This particular mutation occurs in nearly 40 percent of affected individuals with a Northern or Eastern European ancestry. Approximately one-third of Asians with Wilson disease have a mutation that replaces the amino acid arginine with the amino acid leucine at position 778 (written as Arg778Leu or R778L). In the Costa Rican population, more than 60 percent of affected individuals have a mutation that replaces the amino acid aspartic acid with the amino acid serine at position 1270 (written as Asp1270Ser or D1270S).

Other types of mutations delete or insert small segments of DNA within the ATP7B gene or introduce a stop signal in the gene's instructions for making copper-transporting ATPase 2. As a result, no protein is produced, or an abnormally small protein is made. These types of mutations usually result in symptoms that are more severe than those caused by mutations that change a single amino acid.

With a shortage of functional protein, removal of excess copper from the body is impaired. As a result, copper accumulates to toxic levels that can damage tissues and organs, particularly the liver and brain.

Other Names for This Gene

• ATP7B_HUMAN
• ATPase, Cu++ transporting, beta polypeptide
• ATPase, Cu++ transporting, beta polypeptide (Wilson disease)
• Copper pump 2
• PWD
• WC1
• Wilson disease-associated protein
• WND

Genomic Location

The symptoms of Wilson disease vary. Wilson disease is present at birth, but the symptoms don’t appear until the copper builds up in the liver, the brain, or other organs.

Some people do not have symptoms of Wilson disease before they are diagnosed with the disease and treated. If you do have symptoms, the symptoms may be related to your liver, nervous system and mental health, eyes, or other organs.

Liver symptoms

People with Wilson disease may develop symptoms of hepatitis, or inflammation of the liver. In some cases, people develop these symptoms when they have acute liver failure. These symptoms may include

• feeling tired
• nausea and vomiting
• poor appetite
• pain over the liver, in the upper part of the abdomen
• darkening of the color of urine
• lightening of the color of stool
• yellowish tint to the whites of the eyes and skin, called jaundice

Some people with Wilson disease have symptoms only if they develop chronic liver disease and complications from cirrhosis. These symptoms may include

• feeling tired or weak
• losing weight without trying
• bloating from a buildup of fluid in the abdomen, called ascites
• swelling of the lower legs, ankles, or feet, called edema
• itchy skin
• jaundice

Nervous system and mental health symptoms

People with Wilson disease may develop nervous system and mental health symptoms after copper builds up in their body. These symptoms are more common in adults but sometimes occur in children. Nervous system symptoms may include

• problems with speech, swallowing, or physical coordination
• stiff muscles
• tremors or uncontrolled movements

Mental health symptoms may include

• anxiety
• changes in mood, personality, or behavior
• depression
• psychosis

Eye symptoms

Many people with Wilson disease have Kayser-Fleischer rings, which are greenish, gold, or brownish rings around the edge of the corneas. A buildup of copper in the eyes causes Kayser-Fleischer rings. A doctor can see these rings during a special eye exam called a slit-lamp exam.

Among people who have nervous system symptoms of Wilson disease, more than 9 out of 10 have Kayser-Fleischer rings. However, among people who have only liver symptoms, 5 or 6 out of 10 have Kayser-Fleischer rings.

Other symptoms and health problems

Wilson disease can affect other parts of your body and cause symptoms or health problems, including

• a type of anemia called hemolytic anemia
• bone and joint problems, such as arthritis or osteoporosis
• heart problems, such as cardiomyopathy
• kidney problems, such as renal tubular acidosis and kidney stones

Doctors diagnose Wilson disease based on your medical and family history, a physical exam, an eye exam, and tests.

Medical and family history

Your doctor will ask about your family and personal medical history of Wilson disease and other conditions that could be causing your symptoms.

Physical exam

During a physical exam, your doctor will check for signs of liver damage such as

• changes in the skin
• enlargement of the liver or spleen
• tenderness or swelling in the abdomen
• swelling in the lower legs, feet, or ankles, called edema
• yellowish color of the whites of the eyes

Eye exam

During a slit-lamp exam, a doctor will use a special light to look for Kayser-Fleischer rings in your eyes.

Doctors typically use blood tests and a 24-hour urine collection test to diagnose Wilson disease. Doctors may also use a liver biopsy and imaging tests.

Blood tests

For a blood test, a health care professional will take a blood sample from you and send the sample to a lab.

Your doctor may order one or more blood tests, including tests that check amounts of

• ceruloplasmin, a protein that carries copper in the bloodstream. People with Wilson disease often have low ceruloplasmin levels, but not always.
• copper. People with Wilson disease may have lower than normal blood copper levels. Acute liver failure due to Wilson disease may cause high blood copper levels.
• liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST). People with Wilson disease may have abnormal ALT and AST levels.
• red blood cells to look for signs of anemia.

Doctors may order a blood test to check for the gene mutations that cause Wilson disease if other medical tests don’t confirm or rule out a diagnosis of the disease.

24-hour urine collection test

For 24 hours, you will collect your urine at home in a special container that is copper-free, provided by a health care professional. A health care professional will send the urine to a lab, which will check the amount of copper in your urine. Copper levels in the urine are often higher than normal in people who have Wilson disease.

Liver biopsy

If the results of blood and urine tests don’t confirm or rule out a diagnosis of Wilson disease, your doctor may order a liver biopsy. During a liver biopsy, a doctor will take small pieces of tissue from your liver. A pathologist will examine the tissue under a microscope to look for features of specific liver diseases, such as Wilson disease, and check for liver damage and cirrhosis. A piece of liver tissue will be sent to a lab, which will check the amount of copper in the tissue.

Imaging tests

In people who have nervous system symptoms, doctors may use imaging tests to check for signs of Wilson disease or other conditions in the brain. Doctors may use

• magnetic resonance imaging (MRI), which uses radio waves and magnets to produce detailed images of organs and soft tissues without using x-rays
• computed tomography (CT) scan, which uses a combination of x-rays and computer technology to create images

Wilson disease may lead to complications, but early diagnosis and treatment can lower your chances of developing them.

Acute liver failure

Wilson disease can cause acute liver failure, a condition in which your liver fails rapidly without warning. About 5 percent of people with Wilson disease have acute liver failure when they are first diagnosed. Acute liver failure most often requires a liver transplant.

Acute kidney failure and a type of anemia called hemolytic anemia often occur in people who have acute liver failure due to Wilson disease.

Cirrhosis

In cirrhosis, scar tissue replaces healthy liver tissue and prevents your liver from working normally. Scar tissue also partly blocks the flow of blood through the liver. As cirrhosis gets worse, the liver begins to fail.

Among people who are diagnosed with Wilson disease, 35 to 45 percent already have cirrhosis at the time of diagnosis.

Cirrhosis increases your chance of getting liver cancer. However, doctors have found that liver cancer is less common in people who have cirrhosis due to Wilson disease than in people who have cirrhosis due to other causes.

Liver failure

Cirrhosis may eventually lead to liver failure. With liver failure, your liver is badly damaged and stops working. Liver failure is also called end-stage liver disease. This condition may require a liver transplant.

Doctors treat Wilson disease with

• medicines that remove copper from the body, called chelating agents
• zinc, which prevents the intestines from absorbing copper

In many cases, treatment can improve or prevent symptoms and organ damage. Doctors may also recommend changing your diet to avoid foods that are high in copper.

People who have Wilson disease need lifelong treatment. Stopping treatment may cause acute liver failure. Doctors regularly perform blood and urine tests to check how the treatment is working.

Chelating agents

Penicillamine (Cupramine, Depen) and trientine (Syprine) are two chelating agents used to treat Wilson disease. These medicines remove copper from the body.

Penicillamine is more likely to cause side effects than trientine. Side effects of penicillamine may include fever, rash, kidney problems, or bone marrow problems. Penicillamine may also reduce the activity of vitamin B6, and doctors may recommend taking a vitamin B6 supplement along with penicillamine. In some cases, when people with nervous system symptoms begin taking chelating agents, their symptoms get worse.

When treatment begins, doctors gradually increase the dose of chelating agents. People take higher doses of chelating agents until the extra copper in the body has been removed. When Wilson disease symptoms have improved and tests show that copper is at safe levels, doctors may prescribe lower doses of chelating agents as maintenance treatment. Lifelong maintenance treatment prevents copper from building up again.

Chelating agents may interfere with wound healing, and doctors may prescribe a lower dose of chelating agents for people who are planning to have surgery.

Zinc

Zinc prevents the intestines from absorbing copper. Doctors may prescribe zinc as a maintenance treatment, after chelating agents have removed extra copper from the body. Doctors may also prescribe zinc for people who have Wilson disease but do not yet have symptoms. The most common side effect of zinc is stomach upset.

Pregnant women should continue treatment for Wilson disease throughout pregnancy. Doctors may prescribe a lower dose of chelating agents for women who are pregnant. Since the fetus needs a small amount of copper, lowering the dose may keep copper at safe levels without removing too much copper.

In most cases, doctors recommend that women continue to take the full dose of zinc during pregnancy. Experts recommend that women with Wilson disease do not breastfeed if they are taking chelating agents. Penicillamine is present in breast milk and can be harmful to a baby. Experts have little information about the safety of trientine and zinc in breast milk.

If Wilson disease leads to cirrhosis, doctors can treat health problems and complications related to cirrhosis with medicines, surgery, and other medical procedures.

If Wilson disease causes acute liver failure or liver failure due to cirrhosis, you may need a liver transplant. A liver transplant cures Wilson disease in most cases.

When you start treatment for Wilson disease, your doctor may recommend avoiding foods that are high in copper, such as

• chocolate
• liver
• mushrooms
• nuts
• shellfish

After treatments have lowered your copper levels and you begin maintenance treatment, talk with your doctor about whether you can safely eat moderate amounts of these foods.

If your tap water comes from a well or runs through copper pipes, have the copper levels in your water checked. Water sitting in copper pipes may pick up copper. Run the water to flush the pipes before you drink the water or use it for cooking. You may need to use a water filter to remove copper from your tap water.

For safety reasons, talk with your doctor before using dietary supplements, such as vitamins, or any complementary or alternative medicines or medical practices. Some dietary supplements may contain copper.

You can’t prevent Wilson disease. If you have a first-degree relative—a parent, sibling, or child—with Wilson disease, talk with your doctor about testing you and other family members for the disease. A doctor may be able to diagnose and begin treating Wilson disease before symptoms appear. Early diagnosis and treatment can reduce or prevent organ damage.