What is Wilson's disease?
Wilson’s disease is a disorder in which you have a higher than normal amount of copper in your body. An overload of copper is poisonous (toxic) and can damage your liver, brain and other organs.The overload is caused by a genetic defect that prevents your liver from being able to metabolise and remove unnecessary amounts of copper from the body as it normally does.
If Wilson’s disease is diagnosed early enough it can be effectively treated. When it is not treated, the disease is always fatal.
The disease is estimated to affect one person in 30,000 worldwide and occurs with about the same frequency in both men and women. Named after the scientist Samuel Kinnear Wilson who identified it in 1912, Wilson’s disease is also known as ‘hepatolenticular degeneration’.
Copper taken in from your diet is absorbed by the small intestine. From here it is bound to a protein that circulates in your blood (albumin) and transported to your liver to be stored. Normally, any copper your body doesn’t use is carried away by bile – a fluid produced by the liver to aid digestion – and excreted from the body. Biliary excretion is the only means of removing copper. When this ‘pathway’ is not working properly an accumulation (build-up) of copper in the body will follow.
This accumulation of copper will lead to serious and possibly irreversible damage to your liver if not treated. When the copper storage capacity of your liver cells (hepatocytes) is exhausted, the copper ‘spills’ into the bloodstream and deposits in other parts of your body, primarily the brain but also the eyes, kidneys and joints.
The liver is the first organ affected by copper accumulation and for around half of the people who have the disease it is the only affected organ. The toxic effect on the liver cells can cause a condition called hepatitis in which the liver becomes inflamed and swollen. With intense, ongoing inflammation a build-up of scar tissue may form in your liver leading to Cirrhosis.
The effects of the build-up of copper on the brain and spinal cord (central nervous system) can lead to mental confusion and physical symptoms such as tremors and clumsiness.
Copper accumulation begins at birth but it may take several decades or more before the liver is overwhelmed and the symptoms of liver disease begin to appear. Symptoms usually appear between the ages of 6 and 40, most commonly in late adolescence or teens.
Symptoms can range from jaundice (a yellowing of the skin and whites of the eyes) to acute liver failure and may include:
- abdominal pain (in the ‘tummy’ or ‘belly’ area between the chest and pelvis)
- swelling caused by fluid in the abdomen (ascites)
- vomiting blood (from bleeding varices).
The toxic effects of copper accumulation on the nervous system can lead to a range of disabling physical symptoms, most obviously:
- clumsiness and loss of physical coordination
- loss of muscle control
- distorted posture, twisting and repetitive gestures
- slowness of movement (bradykinesia)
- tremors in the arms, legs and head.
The disease may cause problems with language and speech including:
a failing voice, slurring, drooling
difficulty in swallowing
loss of memory and mental confusion.
Around a third of people with Wilson’s disease may experience psychiatric symptoms such as:
- personality change
- uncharacteristic, possibly bizarre behaviour
- worry or anxiety (neurosis)
- depression and mood swings
- suicidal or homicidal thoughts
- delusions or hallucinations (psychosis).
A characteristic clinical sign of Wilson’s disease is a rusty or coppery brown ring around the cornea of your eye, known as the Kayser-Fleischer ring. These rings are not always visible to the naked eye and are only present in around 50% of people with the disease.
Because it has a genetic cause it is not possible to prevent Wilson’s disease.
The large number of possible mutations so far detected in the ATP7B gene (approaching 300) prevents screening for Wilson’s disease in the general population. However, in people with abnormal copper levels that raises suspicion of the disorder, doctors will test for the mutation.
A DNA profile for close family members of a person with Wilson’s disease is recommended, particularly for brothers and sisters as they have a one in four chance of developing the disease. You may wish to talk to a genetic counsellor to find out more about an inherited disorder in your family. You can be referred for counselling by a GP or hospital consultant following diagnosis.
Carriers of Wilson’s disease may have only small abnormalities in their copper metabolism and are very unlikely to become ill. Most people with Wilson’s disease have no family history of the disease.
Diagnosis of Wilson’s disease is based on abnormal liver tests, signs of psychiatric illness and evidence of Kayser-Fleischer rings (a rusty or coppery brown ring around the cornea of your eye).
In terms of psychiatric or neurological signs of Wilson’s disease, unexplained symptoms such as tremors and clumsiness together with a dramatic personality change will raise suspicion of the disorder.
If Wilson’s disease is suspected, an ophthalmologist (a doctor who specialises in the diagnosis and treatment of eye disorders) will carry out a slit-lamp eye examination to confirm the presence of Kayser- Fleischer rings. The slit-lamp is a type of microscope with a high-intensity light beam attached to provide a highly magnified view of your cornea.
Liver function tests (LFTs)
Liver function tests are used to indicate whether your liver is inflamed (hepatitis), damaged or not working properly. They measure levels of certain enzyme and protein substances in your blood that may alter when liver damage is present.
Doctors will measure levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These are liver enzymes which indicate the degree as well as the possible causes of inflammation. 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.
Further blood tests
A simple blood test will be carried out to measure copper in your blood. There may also be a urine test, measuring copper excretion passed into urine over 24 hours. An increase of copper is usually found in urine, but not always.A caeruloplasmin concentration test is performed to measure levels of another copper-carrying protein, caeruloplasmin. Levels of this protein in the blood are likely to be lower than normal.
A liver biopsy may be used to measure the amount of copper (hepatic copper concentration) in your liver. All people with Wilson’s disease will have increased amounts.
Imaging equipment such as magnetic resonant imagery (MRI) or computerised tomography (CT) may be used to examine a specific area of the brain known as the basal ganglia, which is responsible for starting and controlling your body’s movements. The same equipment may also be used to scan your abdomen.
Treatment for Wilson’s disease is aimed at removing the excess copper from your body and preventing it from building up again. This is primarily therapy with de-coppering (‘chelating’) agents.
With early detection and successful treatment it is possible for you to enjoy a healthy life. This type of treatment is known as maintenance therapy and is lifelong.
In the UK, copper-chelation therapy is most commonly used and is begun as soon as diagnosis is made. In chelation therapy the drugs D-penicillamine (cuprimine or depen) or trientine dihydrochloride (syprine) are given to remove copper from your body.
Penicillamine is a drug related to penicillin (but without the antibiotic properties) and is the first choice medication. It is generally successful in preventing or repairing the effects of copper overload unless your liver disease has become very severe. However, around 30% of people are resistant to penicillamine and therefore trientine may be used instead.
Taken in tablet or capsule form, these drugs work by binding with the copper which is then passed from your body in urine.
Medication with penicillamine may have common side effects such as diarrhoea, loss of appetite and nausea. If these persist, you must alert medical staff. Penicillamine can, however, have more serious side effects such as:
- 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.
These side effects occur in around one in ten people. Penicillamine is also used to treat rheumatoid arthritis, kidney stones and other conditions. Potential side effects should be known to medical staff who will closely monitor you. If necessary, dosage of the drug may be lowered. Trientine is likely to have fewer side effects but should also be monitored. A new chelating drug called tetrathiomolybdate is being trialled for future treatment.
It may take up to three months before you notice any improvement in your condition from chelation therapy.
Another therapy uses zinc acetate (galzin). Zinc is known to block the absorption of copper by inducing a protein that binds copper in your intestinal cells. The copper is then lost in the faeces (stools) as the intestinal cells are shed into the gut. Because zinc does not remove copper from the body but blocks the absorption of copper from the diet a course of chelation therapy is used to first lower copper levels.
This medication is also taken orally. It has the benefi t of having fewer (if any) side effects than chelation therapy and is becoming more common. However, it does take considerably longer for the zinc to become effective (four to eight weeks).
It is likely you will be advised to follow a diet that is low in copper. Normally a person absorbs about 4mg of copper daily. This may mean reducing your intake to less than 1mg a day.
Who will be looking after me?
In hospital it is likely you will be treated either by a specialist in liver disease called a hepatologist, a specialist in digestive disorders called a gastroenterologist or a specialist in blood disorders called a haematologist.
Where you may have other conditions or problems caused by Wilson’s disease, additional specialists may be involved in your care. These are likely to be a neurologist (brain) or nephrologist (kidneys).
Looking after yourself
A low copper diet does not mean you have to avoid copper completely. As many foods contain copper, reducing and balancing your intake of certain foods (rather than steering clear of them) is the most realistic way of getting the nutrients you need. Your doctor or a dietician can advise you on managing your diet to achieve this.
The following foods are commonly known to contain a very high concentration of copper:
- dried fruits such as raisins, dates and prunes
- dried beans such as soy, lima, pinto and even baked beans
- dried peas and lentils
- grains such as whole wheat, barley and millet
- soya products such as soya milk and tofu
- offal such as liver, heart and kidneys
- shellfish such as oysters, mussels, shrimps and prawns.
This list is by no means exhaustive. The copper content in foods can also vary depending on a number of factors such as the location of the soil in which the food was grown (copper-containing compounds may be used in farming or agriculture) or the method or utensils used to process the food.
It is also recommended that you try to drink distilled or ‘de-mineralised’ water rather than water from a tap that may have flowed through copper pipes.
If you are being treated with penicillamine you may require further supplements of vitamin B. This is because penicillamine can increase your body’s need for pyridoxine (vitamin B6). It is useful to ask your doctor if you require supplements and if these should be prescribed or bought from a pharmacy.
Anyone with a liver condition should approach alcohol with caution. It is a good idea to reduce your consumption to below recommended levels 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.
Please visit the support section of our website for information on Support groups in your area.
New clinical trial
The British Liver Trust is helping recruit patients for a new research study to evaluate the efficacy and safety of a new therapy against Wilson's disease. If you are a newly diagnosed Wilson Disease patient you may be eligible to join the trial that is currently underway, if you meet the following criteria:
- Male or female, aged 18 years or older
- Have normal or elevated blood free copper levels
- Treated with chelation or zinc therapy for 24 months or less
- In otherwise general good health
For further information about this study, please go to https://clinicaltrials.gov/ct2/show/NCT02273596?term=WTx101&rank=1
If you would like to discuss possible participation at any of the UK centres please contact: Professor Aftab Ala, Consultant Hepatologist, Royal Surrey County Hospital NHS Foundation Trust, Email: firstname.lastname@example.org
The Trust has been donated the use of the following video discussing the physiology of Wilson's Disease – it is aimed at medical students but after asking for feedback, some patients have also said they find it useful. It can be quite technical, so please discuss any content that you are unsure about with your medical team.