What causes Wilson’s disease?
Wilson’s disease and copper
People with Wilson’s disease have too much copper in their body. Although we all need some copper, too much is poisonous. It damages the liver and other parts of the body in different ways and causes a range of health problems.
Usually your liver would control copper levels by adding it to bile, a fluid made by your liver which helps you digest food. As part of bile, the extra copper goes through your gut and your body gets rid of it in your poo.
In Wilson’s disease, a faulty gene (ATP7B) means you can’t make the protein responsible for adding copper to bile. So you can’t get rid of all the extra copper. And because you still take in copper from your diet, it builds up in your body.
Copper levels build up from birth, but this usually happens very slowly. It can take years or even decades before any symptoms develop.
How do high copper levels affect the body?
The first place extra copper is stored is in your liver cells. At high levels copper damages these cells and they die. This makes your liver inflamed and swollen, which is called hepatitis. If the inflammation lasts for a long time, your liver can also become scarred (fibrosis). This scarring can get more severe over time and lead to cirrhosis.
Cirrhosis is a very serious stage of liver disease. In compensated cirrhosis the liver can still do its jobs well enough. But if there is more scarring than there is healthy liver, then it can’t work properly. This is known as decompensated cirrhosis. Cirrhosis can lead to liver failure and liver cancer. Read more about cirrhosis and its complications.
If even more copper builds up and your liver can’t store it, it is carried to other parts of your body in your blood. Copper then starts to build up in places that don’t usually store copper, mainly the brain but also the eyes, kidneys, joints and heart.
Wilson’s disease affects more organs than the liver in about half of people with the condition. Depending where the copper builds up, it can cause different problems.
Copper building up in your brain and central nervous system can lead to confusion, physical tremors, and problems with coordination or clumsiness. The effects on the brain can lead to poorer performance at work or school and psychiatric illnesses.
Wilson’s disease can also affect how well your kidneys work. And can lead to weak, brittle bones (osteoporosis). Women may develop irregular periods, have problems with getting pregnant and may be more likely to have a miscarriage.
How is Wilson’s disease inherited?
Wilson’s disease is caused by a faulty gene called ATP7B. Genes are the instructions that tell our body cells how to grow and what to do. They are passed on from parent to child. You have 2 copies of most of your genes, one inherited from each parent.
When genes are copied, mistakes can happen. A bit like making a spelling mistake if you are copying some writing. A lot of the time this doesn’t matter. But sometimes the mistake means the gene doesn’t work properly anymore – it is faulty.
In lots of genetic diseases, including Wilson’s disease, your body can manage with one healthy gene and one faulty one. So people can have a faulty gene and not know about it. These people are called carriers or heterozygotes. People who have either 2 faulty genes or 2 healthy genes are scientifically called homozygotes. Although Wilson’s disease is very rare, up to 1 in 100 people may carry a faulty copy of the gene.
People only develop Wilson’s disease if they have a faulty gene from both their mother and their father. The medical name for this is an autosomal recessive disorder.
Everyone has 2 copies of the gene, so there is a 50% (1 in 2) chance of a child inheriting 1 particular copy of a parent’s 2 genes. So you can work out the probability that 2 people will have a child who has Wilson’s disease, if one or both of them carry the faulty gene.
If both parents are carriers of the faulty gene (they both have one faulty and one healthy copy), on average each child has:
- a 25% (1 in 4) chance of inheriting 2 faulty genes and developing Wilson’s disease
- a 50% (2 in 4, which is the same as 1 in 2) chance of inheriting 1 faulty and 1 healthy gene and being a carrier like their parents
- a 25% (1 in 4) chance of inheriting 2 healthy genes
These chances are the same each time parents who are both carriers have a child. Already having a healthy child or a child with Wilson’s disease doesn’t affect the chances for any more children they have in the future.
Most people with Wilson’s disease have no family history of the disease. This is because it is usually inherited from parents who are carriers of the faulty gene and don’t have the disease themselves.
You will be offered a test for the faulty gene (genetic testing) if your doctor suspects you have Wilson’s disease, for example because of a problem with your copper levels.
There are lots of different ways that this gene can be faulty, so it isn’t possible to check every person in case they have it. Scientists estimate there are at least 600 different mistakes that stop it working properly. If you are diagnosed with Wilson’s disease, you might have testing to pinpoint the mistakes in your genes (molecular diagnosis). Close relatives can then be tested to check for the same mistakes.
Doctors strongly recommend that people closely related to someone who has been diagnosed with Wilson’s disease are checked for the faulty gene (genetic testing). This includes parents, children, and brothers and sisters of the affected person. It is especially important for their brothers and sisters to be checked as they have a 1 in 4 chance of also developing Wilson’s disease.
If someone has a faulty gene they will have tests for Wilson’s disease. Finding the disease before symptoms develop means treatment can be started at an earlier stage when it is even more effective.
It can help to talk to a genetic counsellor to find out more about an inherited disorder in your family. Ask your GP or hospital consultant to refer you to a genetic counsellor if you or someone in your family have been diagnosed with Wilson’s disease.
What are the symptoms of Wilson's disease?
Copper starts to build up from birth, but this usually happens very slowly. Most people don’t notice any signs that something is wrong for many years. Symptoms of Wilson’s disease usually appear between the ages of 6 and 40, most commonly in people’s late teens.
People who are diagnosed with Wilson’s disease after genetic testing may not have any symptoms.
Because symptoms take years to develop, there can already be serious damage so it’s important to tell a doctor immediately if you develop any of the symptoms below.
Liver symptoms often mean you have liver damage or even liver failure. They include:
- yellowing of the skin and whites of the eyes (jaundice), this can be hard to notice if you have black or brown skin
- pain in the tummy (abdomen)
- swelling or bloating of your tummy (ascites)
- vomiting blood from bleeding veins (varices) in your food pipe.
If copper has started to build up elsewhere in your body it can cause a range of different types of symptoms.
The nervous system can also be affected by high copper levels. Symptoms include:
- clumsiness and loss of physical coordination
- loss of muscle control
- contractions (dystonia)
- distorted posture, twisting and repetitive gestures
- slowness of movement (bradykinesia)
- tremors in the hands, arms, legs and head.
Wilson’s disease may cause problems with language and speech. These include:
- a failing voice or slurring your words
- difficulty in swallowing (dysphagia).
Psychological or psychiatric symptoms develop in around a third of people with Wilson’s disease. These changes may be small, particularly in the early stages, but in rare cases they can be extreme. These include:
- personality changes
- uncharacteristic or bizarre behaviour
- worry, anxiety (neurosis) or loss of confidence
- depression and mood swings
- loss of memory or mental confusion
- suicidal or homicidal thoughts
- delusions or hallucinations (psychosis).
How is Wilson’s disease diagnosed?
Wilson’s disease is diagnosed based on a combination of things including abnormal liver tests, clinical features such as signs of psychological or psychiatric illness, evidence of Kayser-Fleischer rings and genetic tests. You might have some or all of these things.
The mix of both psychiatric and physical symptoms can make Wilson’s disease difficult to diagnose. Symptoms are often hard to tell apart from those of other diseases (non-specific), particularly other types of liver disease.
Different symptoms may also develop separately rather than appearing together at once. Personality changes that come on slowly can be especially hard to link to Wilson’s disease.
Liver blood tests (sometime called liver function tests or LFTs) can show if your liver is inflamed, damaged or not working properly. They measure levels of substances in your blood that can change when your liver is damaged.
Doctors will measure levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These liver enzymes give doctors an idea of how much inflammation there is. They leak into the blood stream when the liver cells are damaged. Levels are usually high in hepatitis. Doctors will be looking for signs of acute or chronic hepatitis, or cirrhosis.
You will have a simple blood test to measure copper levels in your blood. Your doctor will also test your blood for levels of the copper-carrying protein, caeruloplasmin. Levels of this protein in the blood are likely to be lower than normal.
Your doctor may also test a sample of your pee (urine) to check how much copper you pass in your pee over 24 hours. This is usually, but not always, higher than normal.
You might have a liver biopsy to measure the amount of copper in your liver (hepatic copper concentration). Most people with Wilson’s disease will have increased amounts of liver copper.
A liver biopsy can also give a very accurate picture of liver damage. Read more about having a liver biopsy.
Genetic testing is much more widely available in the past. You might have testing to check for the faulty gene that causes Wilson’s disease, including an analysis that pinpoints the specific faults in the genes (molecular diagnosis). Very soon everyone with Wilson’s disease will have a genetic analysis available.
Commonly used imaging tests include:
- an MRI or CT scan of the part of the brain known as the basal ganglia, which is responsible for starting and controlling your body’s movements
- MRI, CT, or ultrasound scan of your liver
- a scan using transient elastography such as a Fibroscan to check your liver for scarring (fibrosis).
How is Wilson’s disease treated?
If Wilson’s disease is diagnosed early enough it can be effectively treated. Treatment is helpful at most stages of the disease. With early detection and successful treatment, people with Wilson’s disease can enjoy a full, healthy life.
Treatment for Wilson’s disease is first aimed at removing excess copper from your body, then stopping copper from building up again. When you are first diagnosed it is likely that you will be advised to follow a diet that is low in copper.
Most people are treated with medicines that remove copper called chelating agents. These medicines work by binding to copper and helping it get passed out of your body in your pee.
You usually start taking a copper-chelating medicine as soon as you are diagnosed with Wilson’s disease. It may take at least three months before your doctor notices an improvement in your clinical condition.
Copper-chelating medicines have to be taken for the rest of your life, to keep removing extra copper from your body. It is very important that you do not stop taking this type of medicine or reduce the dose, unless your doctor tells you to. People have died because they stopped taking these medicines or didn’t take enough.
D-penicillamine is the first-choice medicine for Wilson’s disease. It is related to penicillin, but it isn’t an antibiotic. It is generally successful in preventing or repairing the effects of copper overload unless your liver disease is already very advanced. Around 3 in 10 (30%) people are resistant to D-penicillamine.
D-penicillamine is taken as tablets or capsules.
D-penicillamine can cause diarrhoea, loss of appetite or make you feel sick (nausea). More serious side effects happen in around 1 in 10 people, they can include:
- joint pain
- skin rash, or itching (pruritus)
- swelling and/or pain in your glands
- losing your sense of taste
- unusual bleeding (clotting problems) or bruising
- muscle weakness, numbness or tingly feeling
- skin changes such as wrinkling or pimples
- a wound that will not heal
- kidney damage
Your doctor will know what the possible side effects are and will monitor you for signs of them. Tell them if you notice any side effects or if they don’t go away.
In some cases you might need to lower the dose of D-penicillamine for a short period of time, you should only do this on your doctor’s advice. For example, you should take a lower dose if you are having any kind of surgical procedure until the wound has healed. Similarly, the dose should be reduced during the last three months of pregnancy and until wound healing after childbirth. It is important to tell doctors that you have Wilson’s disease and are taking D-penicillamine.
D penicillamine can make your body need more vitamin B6 than usual. So some people need to take a weekly B vitamin supplement.
Trientine usually causes fewer and less serious side-effects than D-penicillamine. You should have regular blood tests to monitor how you respond to trientine.
In the UK trientine is usually given to people who are either intolerant to D-penicillamine, have life-limiting side effects from D-penicillamine, or have a very low platelet count. It is prescribed and dispensed from approved Wilson’s disease specialist centres across the UK.
There are two formulations of trientine available in the UK, these are trientine dihydrochloride (TETA 2HCL) and trientine tetrahydrochloride (TETA 4HCL).
Another therapy uses zinc acetate (Galzin). Zinc is known to stop your gut absorbing copper from your food. Zinc prompts your gut cells to make a protein that binds to copper and traps it there. Your gut regularly sheds these cells, along with the copper, and it all passes out of your body in your poo.
Because zinc reduces the amount of copper your body takes in, rather than getting rid of copper that’s already built up, you need to take a course of chelation therapy first. Zinc is approved mainly for maintenance therapy or for treating people without symptoms. It is generally the third treatment option for adults, after D-penicillamine and trientine.
Zinc acetate is taken by mouth. It has the benefit of having fewer (if any) side effects than chelation therapy. However, it does take considerably longer for zinc to become effective (four to eight weeks).
An international clinical trial for a new copper-chelating medicine is underway, including in the UK. It is testing a once a day tablet therapy, which (unlike D-penicillamine or trientine) would potentially reduce the risk of muscle weakness and numbness (neurological deterioration). There are other clinical trials in progress that compare trientine and D-penicillamine head-to-head.
Future treatments, in particular gene therapy, are being actively studied in Wilson’s disease.
A small number of patients with Wilson’s disease do not respond to copper-chelating treatment. In some cases this is because the disease is already very advanced and in others it may be because there is more than one cause of liver disease.
In these circumstances, a liver transplant may be the only remaining life-saving treatment option. Read detailed information about liver transplants.
It is likely you will be treated either by a specialist in liver disease called a hepatologist or a specialist in digestive disorders called a gastroenterologist.
Where you may have other conditions or problems caused by Wilson’s disease, additional specialists should be involved in your care. These are likely to be a neurologist (brain), nephrologist (kidneys) or haematologist (blood).
You may also see a psychiatrist for additional support.
Diet and Wilson’s disease
After being diagnosed with Wilson’s disease you will probably need to follow a low copper diet for a short time. This gives medicines that lower the amount of copper in your body time to work.
If the medicines are working well and your condition is stable, you probably won’t need to carry on following a strict low copper diet in the long term. Your doctor or dietitian will advise you on this.
In general, eating a well-balanced diet helps you and your liver stay healthy. Read more about what that means and what foods are good for you.
Try to drink distilled or ‘de-mineralised’ water rather than water from a tap that may have flowed through copper pipes. Water from a tap can be filtered – ask your doctor or dietitian about the best ways to do this.
Normally a person absorbs about 4mg of copper a day from their food and drink. But you may need to reduce this to less than 1mg a day. A low copper diet does not mean you have to totally avoid foods that contain copper. Many foods contain copper, so reducing how much you eat certain foods (rather than steering clear of them) is the most realistic way of getting the nutrients you need.
If you develop cirrhosis you may need to follow special diet advice. Read more about diet and cirrhosis.
Foods known to contain higher concentrations of copper include:
- shellfish such as scallops, oysters, crab, clams, prawns and mussels
- offal such as liver and liver pate, kidneys and heart
- cocoa powder and dark chocolate
- all nuts such as cashews, brazil nuts, walnuts and peanuts
- seeds such as sunflower and pumpkin
- candied or dried fruits such as cherries, raisins, dates and prunes
- wholegrain breakfast cereals such as bran and puffed wheat
- beans such as soya (edamame), butter beans, pinto beans and even baked beans
- soya products such as soya milk and tofu
The copper content in foods can also vary depending on things such as where the food was grown, how it was grown, and how it has been processed. Speak to a dietitan if you have any questions about the copper content of the foods you eat. You can also download a guide to the copper content of common foods eaten in the UK from the Wilson’s Disease Support Group UK website.
If you are being treated with D-penicillamine you might need weekly supplements of vitamin B. This is because D-penicillamine can increase your body’s need for vitamin B6 (pyridoxine). Ask your doctor if you need to take vitamin B supplements and if they can be prescribed or if you should buy them from a pharmacy.
Because it has a genetic cause it is not possible to prevent Wilson’s disease.
Close relatives of people who have been diagnosed with Wilson’s disease are recommended to have genetic testing to see if they are at risk.
Anyone with a liver condition should approach alcohol with caution. It is a good idea to reduce your consumption to below recommended levels (no more than 14 units a week) or abstain from drinking if you can.
Drinking alcohol is likely to speed up and worsen the impact of Wilson’s disease. If you have cirrhosis it is sensible to avoid alcohol completely.
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