Wilson's Disease

What is Wilson's disease?

Wilson's disease is a condition where too much copper builds up in the body. It is a rare inherited disorder that affects about 1 in 30,000 people. It is named after Dr Samual Wilson who first described the disorder in 1912.

If you inherit the genetic fault in Wilson's disease, your body is not able to get rid of copper. Copper is a 'trace metal' which is in many foods. You need tiny amounts of copper to remain healthy. Normally, the body gets rid of any excess copper. People with Wilson's disease cannot get rid of excess copper and so it builds up in the body, mainly in the liver, the brain, the cornea and kidneys.

Too much copper in the liver cells (the hepatocytes) is harmful and leads to liver damage. Damage to brain tissue mainly occurs in an area called the lenticular nucleus. Hence, Wilson's disease is also called 'Hepatolenticular Degeneration'. If left untreated, the damage becomes severe and eventually fatal.

What causes Wilson's disease?

In Wilson's disease, a particular gene on chromosome 13 does not work. The gene is called ATP7B. This gene normally controls the way the liver cells get rid of excess copper. Normally, the liver cells pass out excess copper into the bile. But, if this process does not work, the copper builds up in liver cells. When the copper storage capacity of the liver cells is exhausted, the copper 'spills' into the bloodstream and deposits in other parts of the body, mainly the brain.

How is Wilson's disease inherited?

Wilson's disease is an autosomal recessive disorder. This means that in order to develop Wilson's disease you need to inherit two abnormal ATP7B genes, one from your mother and one from your father.

• 1 in 4 chance that the child will have Wilson's disease by inheriting the abnormal ATP7B gene from both parents)
• 2 in 4 chance that the child will not have Wilson's disease, but will be a carrier by inheriting the abnormal ATP7B gene from one parent but the normal gene form the other parent.
• 1 in 4 chance that the child will not have Wilson's disease, and will not be a carrier by inheriting the normal gene from both parents.

What are the symptoms and problems of Wilson's disease?

Although the genetic defect is present at birth, it takes years for copper to build up to the level where it is damaging. Symptoms typically start to develop between the ages of 6 and 20, most commonly in the teenage years. However, you can first develop symptoms in middle age.

Liver problems

Symptoms of liver problems often develop first. The toxic effect on the liver cells can cause hepatitis (inflammation of the liver) which may cause jaundice, abdominal pain and vomiting. If left untreated, damage to liver cells caused scarring of the liver (cirrhosis). Eventually severe cirrhosis and liver failure develop in untreated cases causing severe problems. (Note: there are various causes of cirrhosis. Wilson's disease is a rare cause of cirrhosis.)

Brain problems

As copper deposits in the brain it can cause various symptoms:

• Physical symptoms such as an odd type of tremor in the arms, slowness of movement, difficulty with speech, writing problems, difficulty swallowing, an unsteady walk, headaches, seizures.
• Psychological symptoms such as depression, mood swings, inability to concentrate. Affected people may become very argumentative and emotional and may seem to have a 'change in personality'.

Left untreated, the accumulation of copper in the brain can lead to severe problems such as severe muscular weakness, severe rigidity, and dementia.

Other problems

Copper may build up in the cornea of the eye. This causes a characteristic feature called Kayser-Fleischer rings - a brownish pigmentation of the cornea. Other features that may develop include anaemia, kidney damage, heart problems, pancreatitis (inflamed pancreas), menstrual problems and repeated miscarriage in women, and premature osteoporosis ('thinnning of the bones').

How is Wilson's disease diagnosed?

If Wilson's disease is suspected, it can be diagnosed by tests.

• A blood test to measure ceruloplasmin. This is a protein that binds copper in the bloodstream. The level is low in nearly all people with Wilson's disease.
• A urine test to measure the amount of copper in the urine. The amount is typically higher than normal.
• An examination of the cornea by an optometrist or eye specialist may show the Kayser-Fleischer rings if they have developed (not present in all cases).
• A biopsy (small sample) of the liver may be taken to look at under the microscope. This can show the excess copper in the liver and the extent of any cirrhosis. See separate leaflet called 'Liver Biopsy'.

If Wilson's disease is confirmed then brothers and sisters should be checked to see if they have the condition. Brothers and sisters of a person with Wilson's disease have a 1 in 4 chance of also having the condition.

How is Wilson's disease treated?

It is essential to treat Wilson's disease. The earlier treatment is started, the better the chance of preventing long-term permanent damage to the liver or brain.

• Penicillamine is a drug used to remove copper from the body (it is called a chelating agent). The penicillamine causes the excess copper from the body to be passed out in the urine. The dose may be reduced to a 'maintenence dose' after about a year when the initial build-up of copper has been cleared.
• Trientine is an alternative to penicillamine. It too is a chelating agent and removes copper from the body.
• Zinc is an option in certain circumstances. Zinc works by blocking the gut from absorbing copper from food. Therefore it does not clear excess copper from the body, but prevents any further build up of copper. Zinc is much less likely to cause side-effects than penicillamine or trientine. It may be an option for people who are diagnosed at the very early stages of the disease and have no symptoms. Also, a switch to zinc may be an option for people who have been initially treated with penicillamine or trientine once the initial build up of copper has been cleared from the body.

Diet

Foods with a high concentration of copper generally should be avoided, at least in the first year of treatment when the excess copper is being cleared from the body. These include: shellfish, nuts, chocolate, mushrooms and organ meats.

What is the outlook prognosis?

• If treatment is begun in the early stages of the disease, it usually works well. You can expect a normal length and quality of life.
• Without treatment, Wilson's disease is usually fatal, usually before the age of 40.
• If symptoms have developed before treatment is started, some of the symptoms improve with treatment, but some may remain permanently. For example, some of the brain symptoms are permanent once they develop. Your specialist will be able advise about which symptoms may go and which may be permanent once treatment is started.

Further help and information

Wilson's Disease Support Group

36 Audley Drive, Lenton Abbey, Nottingham, NG9 2SF
Web: www.wilsonsdisease.org.uk

British Liver Trust

2 Southampton Road, Ringwood, BH24 1HY
Tel: 0870 770 8028 Web: www.britishlivertrust.org.uk