Also Known As
Hepatolenticular Degeneration
This article was last reviewed on
This article waslast modified on 5 September 2017.
What is it?

Wilson’s disease is an inherited disorder of copper metabolism that leads to the deposition of copper in various tissue and organs, particularly the liver and brain. It is also known as copper storage disease, hepatolenticular degeneration and inherited copper toxicity. Copper is an essential mineral present in our food. It is incorporated into enzymes that play a role in the regulation of iron metabolism, formation of connective tissue, energy production in cells, the production of the skin pigment melanin, and the function of the nerves and brain. Copper is absorbed in the intestines, bound to a carrier protein, transported to the liver, and then stored or used – with the excess removed into the bile and removed from the body in the stool with a little excreted in the urine. Normally 95% of the copper found in the blood is bound to caeruloplasmin, a protein involved with iron metabolism which is produced in the liver.

Wilson's disease is an autosomal recessive disorder which means that two abnormal gene copies (one from each parent) are needed to cause the disease. Those with only one defective copy are carriers and can pass the mutation on to their children but do not have symptoms of the disease themselves. The gene mutations causing Wilson’s disease are in a gene called ATP7B. This gene is needed to attach copper to caeruloplasmin and to excrete copper into the bile. An alteration in both copies of the gene leads to excess copper storage in the liver and to a decrease in the caeruloplasmin level in the blood. As the copper levels increase the liver becomes damaged, and the copper spills into the blood. The free (unbound) copper concentrations in the blood increase and can cause damage other organs such as the brain and kidneys. Affected patients may have signs and symptoms of liver disease, neurological (nerve) damage, or both. The severity of the condition depends partly upon the gene mutations present but will also vary from person to person. About 1 in 30,000 people in the UK population have Wilson’s disease and as many as 1 in 90 are estimated to be carriers. There are currently over 260 known mutations of the ATP7B gene seen in Wilson’s disease patients. Only a few of these mutations are common, and they vary in frequency throughout the world. Affected patients may have two copies of the same genetic mutation or two different mutations. Wilson’s disease patients with liver disease frequently have symptoms starting in early childhood, those with brain involvement may have neurological and psychiatric symptoms beginning in their teens or early twenties, but the age range for both can vary from about three years old to over fifty. Deposits of copper in the liver can lead to acute, chronic, and progressive hepatitis and cirrhosis and cause signs and symptoms such as

  • jaundice
  • tiredness
  • tummy pain
  • nausea
  • ascites (a build-up of fluid in the abdomen)

Patients with brain involvement may have a range of physical symptoms including

  • stiff face muscles
  • tremor
  • abnormal eye movements
  • altered gait (the way a person walks)
  • difficulty with walking, speaking, and swallowing

They may also experience behavioural changes such as depression, paranoia, impulsiveness, obsessive behaviour, aggression, and a shortened attention span. About 50% of those with liver disease and 90% of those with brain involvement will have Kayser-Fleischer rings which are deposits of copper in a ring around the cornea. These can be seen with an eye test called a slit lamp examination. Some patients may also have anaemia, are easily bruised, joint pain and/or kidney problems.

Left untreated, Wilson’s disease tends to become progressively worse and is eventually fatal. With early detection and treatment most of those affected can live relatively normal lives. Liver and neurological damage that occurs prior to treatment may improve but it is often permanent.

 

Accordion Title
About Wilson's Disease
  • Tests

    Various tests are used are to diagnose Wilson’s disease and to evaluate its severity. The tests will also help to distinguish between those who have the disease and those who are carriers, rule out other causes of liver and neurological disease and to monitor the effectiveness of treatment.  Testing is also used to identify family members who are pre-symptomatic or carriers and sometimes for prenatal evaluation.

    Laboratory Tests
    Care must be taken to avoid external copper contamination in sample collection.  Repeat testing of abnormal results may be recommended.  Test results of people who are carriers may overlap with those who have Wilson’s disease but are pre-symptomatic.  Other liver diseases may also result in excess copper storage and increased copper in the blood.  Acute cases of Wilson’s disease may be difficult to distinguish from other forms of liver disease.  Testing may include:

    • Caeruloplasmin– requested to help diagnose Wilson’s disease. Its level is usually decreased but about 5% of patients with Wilson’s disease who have neurological symptoms will have normal caeruloplasmin levels as will up to 40% of those with liver symptoms.
    • Total serum copper – may be requested to help diagnosis, but it is of limited use. Its level is usually decreased in Wilson’s disease.
    • Free serum copper (non-caeruloplasmin-bound) – used to diagnose and monitor, usually increased in Wilson’s disease.
    • 24-hour urine copper – used to diagnose and monitor, usually increased in Wilson’s disease.
    • Liver copper – a liver tissue biopsy collected to help diagnosis.  Its level is usually increased in Wilson’s disease but deposits of copper may not be evenly distributed in the liver and so the test may occasionally be negative in patients with the disease.
    • Molecular genetic testing – This is specialised testing that is available from a limited number of reference or research laboratories.  It is used to diagnose Wilson’s disease and identify mutations and carriers.  Some prediction of disease severity can be established based upon the mutations present but testing cannot determine the severity, complications, or organ involvement that will be experienced by a specific individual.  The severity and course of the disease can vary significantly, even between family members with the same mutations. The ATP7B gene mutations most prevalent in a region or ethnic population may be found.  If the mutations have been identified in a patient with Wilson’s disease then the family members can be tested for these. Gene sequencing can be performed to examine the entire gene for mutations. This is the most thorough test. Linkage analysis can also be carried out. This requires blood from parents, siblings, and an affected family member.

    Other tests may be performed to evaluate organ function and blood cell status, including:

    • FBC (Full Blood Count)
    • Liver function tests (LFTs) 

    Non-Laboratory Tests

    • Eye exam – slit lamp examination for Kayser-Fleischer rings in the cornea
    • MRI (magnetic resonance imaging) scan
    • CT (computerised tomography) scan

     

  • Treatment

    There is no way to prevent or cure Wilson’s disease but it can be successfully managed.  Symptoms, complications and response to treatment will vary from person to person, even within families who have the same genetic mutations.

    In patients with symptoms of Wilson’s disease the goals of treatment are to decrease excess copper stores, prevent their recurrence, preserve liver, neurological, and kidney function, and to minimise complications associated with the condition and with the medications used to treat it. 

    Patients who do not have symptoms but have been diagnosed as having Wilson’s disease, such as siblings of affected patients, will usually be treated to decrease any excess copper that is present and to prevent its build-up.  Those who are carriers of Wilson’s disease should receive genetic counselling but do not usually require any treatment. 

    Affected patients are put on a low copper diet.  Most are treated first with one of two chelating agents, D-penicillamine or trientine (triethylene tetramine dihydochloride), to increase urinary excretion of copper and decrease copper stores.  Patients must be monitored for side effects as the medications can decrease red blood cell, white blood cell and platelet counts and can cause nausea, fever, and skin conditions.  Some patients must take these medications long term. Others can switch to zinc therapy once copper stores have normalised.  High doses of zinc inhibit the absorption of copper. Antioxidants such as vitamin E may be recommended to help prevent liver and other tissue damage.

    Copper dietary restriction and treatment must be continued throughout the patient’s life.  Treatments may be changed but should never be discontinued.  In some severe cases liver transplantation may be necessary.