Wilson's Disease

What is Wilson’s disease?

Wilson’s disease is an inherited disease in which excess copper cannot be sufficiently excreted from the body, leading to a build-up of copper particularly in the liver, the brain and the eyes.

Copper is a mineral the body needs. Normally, copper in excess of what we need is removed from the body by the liver through the bile. In Wilson’s disease this system does not work as it should.

The result is:

excretion of copper falls → copper builds up in the liver → over time it passes into the blood and other organs → damage can develop in various organs, the liver and the nervous system chief among them.

The most important characteristic of Wilson’s disease is that it can be treated effectively when it is caught early. Untreated, it can lead to serious liver and neurological problems.

Why does Wilson’s disease occur?

Wilson’s disease arises from changes in a gene called ATP7B.

The disease comes about through genes passed on from both parents and is inherited in an autosomal recessive way. This means that for the disease to appear, the person must receive the faulty gene from their mother and from their father.

If both parents are carriers, then for each pregnancy the chances for the child are:

• 25% of developing Wilson’s disease,
• 50% of being a carrier,
• 25% of being unaffected.

For this reason it is very important that the siblings and first-degree relatives of a person diagnosed with Wilson’s disease are assessed.

Is Wilson’s disease common?

Wilson’s disease is a rare disease. Traditional estimates put it at about one in 30,000 people.

But genetic research shows that the gene changes that can cause the disease may be commoner than that. In some people the diagnosis may not have been made because the disease runs a very mild course or gives no symptoms for a long time.

At what ages does it appear?

Because Wilson’s disease is genetic it is present from birth, but the symptoms appear after copper has built up over time.

Most patients are diagnosed in childhood, adolescence or young adulthood. Even so, Wilson’s disease is not a disease of the young alone; it can also appear later in life.

For this reason Wilson’s disease should not be excluded entirely on the grounds of the patient’s age alone in unexplained liver disease.

Which organs does Wilson’s disease affect?

The organs most often affected are:

the liver – the brain and nervous system – the eyes.

But other organs can also be affected, such as the kidneys, the blood cells, the bones, the joints and, less often, the heart.

What symptoms may be seen in the liver?

Wilson’s disease sometimes comes to light only through raised liver enzymes on routine blood tests.

In some patients there may be:

• Weakness,
• Loss of appetite,
• Nausea,
• Abdominal pain,
• Jaundice,
• Enlargement of the liver and spleen,
• Fluid collecting in the abdomen (ascites),
• Swelling of the legs.

Over time the disease can lead to chronic hepatitis, fibrosis of the liver and cirrhosis.

Rarely, Wilson’s disease can present for the first time as sudden, severe liver failure. This requires emergency treatment.

What are the neurological and psychiatric symptoms?

When copper builds up in the brain, different symptoms can appear.

These may include:

• Tremor in the hands or the body,
• Disturbance of speech,
• Slowing of movement,
• Stiffness of the muscles,
• Involuntary movements,
• Disturbance of balance and coordination,
• Difficulty swallowing.

In some patients the first symptoms may be changes in behaviour or mood:

• Changes in personality,
• Irritability,
• Depression,
• Anxiety,
• An unexplained fall in performance at school or work,
• Changes in behaviour.

In a young person in particular, unexplained liver disease together with neurological or behavioural changes should raise the possibility of Wilson’s disease.

What is the Kayser-Fleischer ring?

This is one of the best known findings of Wilson’s disease.

Copper can build up around the transparent layer of the eye called the cornea and form a brown, gold or greenish-brown ring. This is called the Kayser-Fleischer ring.

The ring cannot always be seen with the naked eye. It is looked for by an ophthalmologist with a slit-lamp examination.

It is seen often in patients with Wilson’s disease who have neurological symptoms in particular.

But there is an important point:

Not seeing a Kayser-Fleischer ring does not definitely exclude Wilson’s disease.

How is Wilson’s disease diagnosed?

The diagnosis of Wilson’s disease is generally not made with a single test.

The patient’s symptoms, family history, eye examination and various laboratory tests are assessed together.

Caeruloplasmin

Caeruloplasmin is a protein that carries copper in the blood.

The caeruloplasmin level is low in a substantial proportion of patients with Wilson’s disease.

But:

a low caeruloplasmin = definitely Wilson’s disease

does not hold.

Caeruloplasmin can be normal in some patients with Wilson’s disease, while low values can be seen in people who do not have it.

The result must therefore be assessed together with the other tests.

Copper in a 24-hour urine collection

The amount of copper is measured in urine the patient has collected over 24 hours.

The amount of copper excreted in the urine is generally increased in Wilson’s disease.

It is one of the important tests both in making the diagnosis and later in monitoring treatment.

Blood tests

Depending on the patient’s situation, the following are assessed:

• ALT and AST,
• Bilirubin,
• Albumin,
• INR,
• A full blood count,
• Caeruloplasmin,
• Other tests of copper metabolism.

In patients with Wilson’s disease who develop sudden liver failure in particular, haemolytic anaemia — the rapid breakdown of red blood cells — may be seen.

Is a liver biopsy needed?

It is not needed in every patient.

A liver biopsy may be done where the blood tests, urine, eye examination and genetic investigations are not enough to establish the diagnosis with certainty.

A biopsy can assess:

• The amount of copper in the liver,
• The degree of liver damage,
• Fibrosis or cirrhosis.

Is genetic testing done?

Yes.

Examination of the ATP7B gene can be important particularly where the diagnosis is uncertain, and in screening members of the family.

Assessing the siblings and other at-risk relatives of a person diagnosed with Wilson’s disease can allow the disease to be caught before it has given any symptoms.

May a brain MRI be needed?

A brain MRI may be done in patients with neurological symptoms.

In Wilson’s disease, changes due to the build-up of copper may be seen in certain regions of the brain, particularly those involved in the control of movement.

Is there a treatment for Wilson’s disease?

Yes. Wilson’s disease is a treatable disease.

The aim of treatment is to remove the excess copper that has built up in the body and to prevent it building up again.

With early diagnosis and regular treatment, many patients can lead a normal or near-normal life.

But there is a very important point:

Treatment of Wilson’s disease generally continues for life.

Even if the patient feels entirely well, they should not stop their medicines without consulting their doctor.

Which medicines are used?

There are two main approaches in treatment.

Medicines that remove copper from the body. These are called chelating drugs. The chief ones are:

• D-penicillamine,
• Trientine.

These medicines help to remove the excess copper from the body.

In marked liver disease in particular, chelating treatments that remove copper occupy an important place in the current approach.

Zinc. Zinc reduces the absorption of copper from the bowel.

In some patients it may be used in maintenance treatment after the initial treatment, or at particular stages of the disease.

Which treatment is suitable is decided according to the patient’s liver and neurological state.

Is monitoring needed during treatment?

Yes. Regular follow-up is an inseparable part of the treatment of Wilson’s disease.

At follow-up, the following may be assessed:

• The patient’s symptoms,
• Liver tests,
• Blood count,
• Kidney function,
• Copper in the urine,
• Other tests of copper metabolism.

The aim is not only to see whether the treatment is working. Over-treatment or under-treatment and the possible side effects of the medicines also have to be identified.

Does diet matter in Wilson’s disease?

At the start of treatment in particular, the doctor may advise reducing foods very high in copper.

Foods rich in copper may include:

• Liver and certain offal,
• Shellfish,
• Certain nuts,
• Chocolate and cocoa,
• Certain mushrooms.

But the main treatment of Wilson’s disease is not diet alone.

Following a low-copper diet in place of drug treatment is not correct.

Needlessly strict diets should also be avoided.

May a liver transplant be needed?

Most patients with Wilson’s disease do not need a liver transplant, given early diagnosis and appropriate drug treatment.

But where Wilson’s disease has led to:

• Acute liver failure,
• Advanced and irreversible liver failure,

a liver transplant can be life-saving.

The 2025 EASL-ERN guideline states that liver transplantation may also be considered under selected conditions in certain patients with very severe, treatment-resistant neurological Wilson’s disease.

Why does screening family members matter?

Because Wilson’s disease is inherited, the following relatives of a person diagnosed with it should be assessed for risk:

• Their siblings,
• Their children,
• Their parents.

The disease may be present even where these people appear entirely healthy.

Making the diagnosis before symptoms appear can allow treatment to be started early and permanent damage to the liver or the brain to be prevented.

The important message

Wilson’s disease is a rare inherited disease of copper metabolism which, caught early, can be treated effectively.

Wilson’s disease should come to mind particularly where there are unexplained raised liver enzymes, chronic liver disease, cirrhosis or neurological symptoms in children and young adults. But the disease can also appear later in life.

The diagnosis does not rest on a single laboratory result. Caeruloplasmin, copper in a 24-hour urine collection, eye examination, assessment of the liver and, where needed, genetic investigation are all assessed together.

The most important point is that, once the diagnosis is made, treatment is continued regularly and generally for life.

This content has been prepared for general information. The diagnosis, treatment and follow-up of Wilson’s disease should be planned by a doctor according to the patient’s clinical features.