Wilson's disease

In the human body, copper plays an important role in the development of healthy bones, nerves, collagen and the skin pigment melanin. Copper is normally absorbed from food and excess copper is excreted through bile. Bile is produced by the liver and carries toxins and waste away from the body, through the digestive system.

In people with Wilson's disease, there is a defective enzyme that results in excess copper not being removed. Instead, it leaves the bloodstream and accumulates in various organs and structures including the liver, brain, spinal cord, eyes and kidneys. About 50% of people diagnosed with Wilson's disease have symptoms that are localized to just their liver.

Copper is toxic in large amounts. As tissues become damaged by the build-up of copper, the healthy tissue is replaced by scar tissue, which cannot perform the normal functions of the organ involved and the organ ceases to work properly.

Wilson's disease affects around one in every 30,000 people. It cannot be cured, but can be very well managed if diagnosed early. The copper accumulation starts from birth, but symptoms can take many years to become apparent. It is typically diagnosed in people between 5-35 years of age and affects men and women equally.

Causes

People have two copies of most genes and inherit one copy from each parent. A genetic disease occurs when one or both parents pass on a mutated gene to a child at conception. In Wilson's disease, a child inherits a copy of the genetic mutation from both their parents.

The gene responsible for Wilson's disease is called ATP7B. When this gene is mutated, excess copper cannot be moved from the liver effectively.

About one in 100 people are carriers of the ATP7B gene. Carriers of the gene do not become ill and do not need medical treatment. When both parents of a child carry it, there is a:

• One in four chance the child will develop Wilson's disease (by inheriting both mutated genes);
• Two in four chance the child will not develop Wilson's disease, but will be a carrier, and;
• One in four chance the child will not have Wilson's disease and not be a carrier.

 

Signs and symptoms

The symptoms experienced by people with Wilson's disease may vary, depending on which organs are affected by the copper accumulation.

Although the condition is present at birth, the symptoms do not become apparent until the copper has accumulated in the organs. Some people diagnosed with Wilson's disease may not even have any symptoms; instead, their condition is discovered during routine physical examinations or laboratory tests.

Liver-related signs and symptoms

Liver symptoms are typically the first to develop. The toxic effects of the copper on the liver cells may cause:

• Nausea;
• Vomiting;
• Loss of appetite;
• Jaundice;
• Weakness;
• Itching;
• Edema - swelling that is usually noticed in the ankles, legs or feet;
• Weight loss;
• Fatigue, and;
• Muscle cramps.

Some people with Wilson's disease may not develop any symptoms until their condition has reached the stage of acute liver failure, which can develop very suddenly.

Central nervous system-related signs and symptoms

Symptoms that affect the central nervous system and mental health often appear once the liver has accumulated a lot of copper.

These symptoms are more often apparent in adults, but can occur in children and include:

• Muscle stiffness;
• Tremors;
• Speech problems;
• Excessive salivation due to problems with swallowing;
• Confusion;
• Dementia;
• Personality changes;
• Depression;
• Anxiety;
• Clumsiness with hands, and;
• Psychosis.

Other signs and symptoms

• Kayser-Fleischer rings - a golden-brown discoloring in the eyes. These result from the build-up of copper in the eyes. People with central nervous system symptoms commonly have these rings, but they are only found in around half the people with liver damage;
• Anemia;
• Arthritis, and;
• Osteoporosis.

 

Methods for diagnosis

Your doctor will ask about your medical history and symptoms and will perform a thorough physical examination.

Genetic testing

When there is an established family history of Wilson's disease, early diagnosis can prevent symptoms and potential organ damage. If a relative has previously been diagnosed with Wilson's disease, genetic testing may be an option, but as there are many mutations that can cause the condition, there is no single test that is appropriate for everyone.

Blood tests

Liver function and full blood counts

Blood tests are used to assess the function of the liver and to measure the levels of red blood cells, white blood cells and platelets. People with Wilson's disease will typically have an abnormal liver function test result and low blood count levels.

Copper levels

Since the copper is deposited into the organs and not circulating in the blood, most people with Wilson's disease actually have a lower-than-normal level of copper in their blood.

Ceruloplasmin levels

Ceruloplasmin is a protein that carries copper in the bloodstream. Most people with Wilson's disease have a lower-than-normal level of this protein in their blood.

Urine test

People with Wilson's disease have abnormally high levels of copper in their urine.

Eye examination

A doctor will use a microscope with a high-intensity light source to check eyes for Kayser-Fleischer rings. Wilson's disease is also associated with a specific type of cataract, called a sunflower cataract, which may also be apparent on examination.

Imaging

To exclude other possible conditions that may be causing neurological symptoms, diagnosis may include imaging scans of the head such as magnetic resonance imaging (MRI) or computerized tomography (CT).

Liver biopsy

To assess damage to the liver and measure the amount of copper that has accumulated, a small sample of liver tissue may be removed (biopsied) for further testing.

Types of treatment

The aim of treatment is to reduce the amount of copper in the body and to control any symptoms. Treatment is lifelong and delays in starting treatment can potentially cause irreversible damage.

Medications

Zinc acetate

Zinc increases the levels of an intestinal protein called metallothionein, which has a high affinity for copper. The metallothionein reduces the absorption of copper and increases its excretion. Zinc can cause an upset stomach for some people.

D-penicillamine and trientine

Copper chelation therapy prompts organs to release copper into the bloodstream, which is then filtered by the kidneys and released into urine.

D-penicillamine is often the primary medication for copper chelation, but it commonly causes side effects such as skin problems, bone marrow suppression and worsening of neurological symptoms.

Trientine works similarly to D-penicillamine, but has fewer associated side effects.

Vitamin B6

Vitamin B6 supplements may help ease nervous system symptoms.

Potassium

Potassium supplements can reduce absorption of dietary copper.

Dietary changes

People with Wilson's disease may be advised to follow a diet that is low in copper, which may include avoiding chocolate, dried beans, dried fruits, mushrooms, nuts, offal, peas, shellfish and wholewheat products. People with poor liver function may be advised to avoid excess alcohol consumption.

Liver transplantation

A liver transplantation may be considered when there is severe liver damage, acute liver failure, or when no other treatment options have proved effective.

Potential complications

Without medical treatment, complications of Wilson's disease can include:

• Liver disease such as hepatitis or cirrhosis;
• Increased susceptibility to infections;
• Disorders of the spleen;
• Anemia;
• Muscle wasting;
• Intellectual and/or physical disability, and;
• Death.

Prognosis

Wilson's disease cannot be cured, but with proper management, a person with Wilson's disease can usually live a normal life. However, people who have advanced Wilson's disease, or rapidly progressive liver failure, can expect serious health consequences.

Prevention

Wilson's disease cannot be prevented, but those with a family history may benefit from being tested for the disease before symptoms appear, as an early diagnosis can reduce or prevent organ damage.