What is Wilson's disease?

Wilson's disease is a rare genetic disorder caused by the accumulation of copper throughout the body.

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 localised 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.

Bile

A fluid made in the liver and stored in the gall bladder.

Bloodstream

The flow of blood within the blood vessels of the circulatory system.

Collagen

A protein that is the main component of various connective tissues.

Digestive system

The series of organs within the body that contribute to the digestion of food. It begins at the mouth and ends at the anus, and includes the stomach, small and large intestines as well as the pancreas, gallbladder and liver.

Enzyme

Molecules (mainly proteins) produced by cells that can drive specific chemical reactions.

Genetic

Related to genes, the body's units of inheritance or origin.

Kidneys

A pair of organs responsible primarily for regulating the water balance in the body and filtering the blood.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Melanin

The pigment responsible for the colour of the skin, hair and the iris of the eye.

Nerves

One or more fibres that transmit signals of sensation and motion between the brain or spinal cord and other parts of the body.

Spinal cord

A bundle of nerve tissue that runs from the brain through the spinal column and connects the brain to the body, transmitting sensory and motor signals.

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.

 

Genes

A unit of inheritance (heredity) of a living organism. A segment of genetic material, typically DNA, that specifies the structure of a protein or related molecules. Genes are passed on to offspring so that traits are inherited, making you who you are and what you look like.

Genetic

Related to genes, the body's units of inheritance or origin.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Mutation

An inheritable change in the base sequence of the genome of an organism.

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;
  • Oedema - 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:

Other signs and symptoms

  • Kayser-Fleischer rings - a golden-brown discolouring 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;
  • Anaemia;
  • Arthritis, and;
  • Osteoporosis.

 

Anaemia

A deficiency in red blood cells or haemoglobin in the body.

Anxiety

A feeling of tension, nervousness and dread about future events. It can trigger physical symptoms such as a rapid pulse or breathing difficulties.

Central nervous system

The part of the body's nervous system that includes the brain and the spinal cord.

Fatigue

A state of exhaustion and weakness.

Jaundice

A yellowing of the skin, the whites of the eyes and the mucous membranes, due to an accumulation of bilirubin in the blood. Often a symptom of liver problems.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Nausea

A sensation of sickness and unease, typically felt in the stomach, often accompanied by the urge to vomit. Nausea is a common symptom with many possible causes.

Psychosis

An abnormal mental state characterised by a loss of contact with reality.

Vomiting

Ejecting the contents of the stomach through the mouth.

Tremors

Unintentional trembling in one or more parts of the body.

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 computerised 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.

Blood tests

During a blood test, blood can be drawn using a needle or by a finger prick. Your blood can then be analysed to help diagnose and monitor a wide range of health conditions.

Bloodstream

The flow of blood within the blood vessels of the circulatory system.

Cataract

A clouding of the lens of the eye.

Computerised tomography

A scan that uses X-rays to create a 3D image of the body. This can detect abnormalities more effectively than a simple X-ray can.

Genetic

Related to genes, the body's units of inheritance or origin.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Magnetic resonance imaging

A type of imaging that uses a magnetic field and low-energy radio waves, instead of X-rays, to obtain images of organs.

Mutations

An inheritable change in the base sequence of the genome of an organism.

Neurological

Of the nervous system, including the brain.

Platelets

Small blood cells found in the blood that are essential for clotting to occur.

Protein

1. One of the three macronutrients in foods that supply the body with energy. Food rich in proteins include meats, legumes and dairy foods. 2. Large molecules, such as antibodies and albumin, that are found in the blood.

Red blood cells

Cells in the blood that transport oxygen from the lungs throughout the body and carbon dioxide from the body to the lungs.

Urine

The yellowish fluid made by the kidneys and moved via the urinary tract out of the body. It contains waste products, excess water and electrolytes.

White blood cells

Cells of the immune system that participate in immune and inflammatory reactions.

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.

Bloodstream

The flow of blood within the blood vessels of the circulatory system.

Bone marrow

The spongy, vascular or fatty tissue found inside bones, responsible for producing blood cells.

Kidneys

A pair of organs responsible primarily for regulating the water balance in the body and filtering the blood.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Neurological

Of the nervous system, including the brain.

Protein

1. One of the three macronutrients in foods that supply the body with energy. Food rich in proteins include meats, legumes and dairy foods. 2. Large molecules, such as antibodies and albumin, that are found in the blood.

Urine

The yellowish fluid made by the kidneys and moved via the urinary tract out of the body. It contains waste products, excess water and electrolytes.

Potassium

A water-soluble compound and major mineral that is essential for maintaining contractions of muscles, including the heart.

Potential complications

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

Anaemia

A deficiency in red blood cells or haemoglobin in the body.

Cirrhosis

Scarring of liver tissue, which the irreversible replacement of normal liver cells by fibrous cells. Cirrhosis is the result of chronic liver damage.

Infections

Entry into the body of microorganisms that can reproduce and cause disease.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Spleen

An organ in the abdominal cavity that is involved in filtering out old blood cells and fighting infection.

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.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

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.