Wilson's Disease

Wilson's Disease (Hepatolenticular Degeneration)

What is Wilson's disease?

Wilson's disease is a condition where too much copper is seen to build up in the body. It is a rare inherited disorder that can affect around 1 in 30,000 people.

In a person with Wilson's disease, one cannot get rid of the excess copper and it then builds up in the body mainly in the liver, the brain, the layer at the front of the eye (called the cornea) and the kidneys.

Wilson's disease is also sometimes called Hepatolenticular degeneration. In the majority of people diagnosed with Wilson's disease, they are diagnosed between the ages of 5 and 35 years but it can also be diagnosed in a younger person and even up to a person whom is in their 70s.

Symptoms of Wilson's disease

The symptoms of Wilson's disease typically start to develop between the ages of six and 20 years. However, one can start developing symptoms even in middle age.

There are different areas of the body that are affected and these can include:

• Liver
  The symptoms of liver problems often develop first. The toxic effect on the liver cells can cause inflammation of the liver (hepatitis) which can present as: jaundice (yellowing of the skin and the whites of the eyes), abdominal pain and vomiting. If left untreated, however, it can lead to damage of the liver cells which results in scarring of the liver (cirrhosis) and also liver failure.
• Brain
  As copper deposits in the brain it can cause various symptoms which include:
  • Physical symptoms which occur earlier on such as tremor, slow movements, difficulty with speech, excess salivation and difficulty with swallowing.
  • Psychological/Psychiatric symptoms such as depression, inability to concentrate and mood swings.

If these brain symptoms are left untreated, the copper accumulation can lead to dementia, rigidity and muscle weakness.

• Other
  Copper may build up in the layer at the front of the eye (called the cornea) and can cause a characteristic feature called Kayser-Fleischer rings (which is a brownish pigmentation in the cornea part of the eye). Other features that can develop include: anaemia, kidney damage, premature 'thinning' of the bones (osteoporosis) and inflammation of the pancreas (pancreatitis).

Causes of Wilson's disease
In Wilson's disease, there is a particular gene on chromosome 13 which does not work and this gene is called ATP7B. This gene will normally control the way the liver cells get rid of excess copper and the liver cells will normally pass out excess copper into the bile. 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 will then spill into the bloodstream and deposits in other areas of the body, such as the brain.

Diagnosis of Wilson's disease
If Wilson's disease is suspected, it can be diagnosed by a variety of tests including:

• Blood tests: A blood test to measure caeruloplasmin (which is a protein that binds to copper in the bloodstream and is low in nearly all people with Wilson's disease) can be done as well as copper, liver function and kidney function tests and a full blood count(to look for any anaemia).
• Urine test: This is done to measure the amount of copper in the urine (This is usually testing urine that one produces over a 24-hour period).
• Eye examination: An eye examination by an optician (optometrist) or an eye specialist (ophthalmologist) can include looking at the layer at the front of the eye (called the cornea) and in Wilson's disease, one can find Kayser-Fleischer rings(brownish pigmentation in the cornea part of the eye) if they have developed. These are however not present in all cases in Wilson's disease.
• Liver biopsy (sample of liver tissue): A small sample (biopsy) of the liver could be taken to look at under the microscope. This can show excess copper in the liver and the extent of any scarring that has occurred of the liver
• Scans: Other tests may also be considered such as an MRI scan of your brain and your kidneys.
• Genetic tests can also be considered to be done to see if any family such as siblings may also have Wilson's disease, if it has already been diagnosed in a close family member.

General Information

Treatment
With regards to the treatment of Wilson's disease, it is very important to start treatment earlier for a better chance of prevention of a long-term, permanent damage to the liver or brain.

• Medications used include:
  • Penicillamine, which is used to remove copper from the body. It passes out the excess copper from the body to urine. The dose can be reduced to a maintenance dose after about a year when the initial build-up of copper has been seen to clear.
  • Trientine is an alternative to Penicillamine. It removes copper from the body.
  • Zinc is an option in certain circumstances. It works by blocking the gut from absorbing copper from food, will not clear excess copper from the body, but prevents any further build-up of copper. Zinc is less likely to cause side-effects than Penicillamine or Trientine. It can be an option for people who are diagnosed at the very early stages of the disease and who show no symptoms. Switching 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.
• If there has been no response to treatment with medications, or one is diagnosed in the late stage of the disease with severe scarring of the liver (cirrhosis) or liver failure, a liver transplant can be an option and this can be life-saving. The long-term outlook after having a liver transplant is usually very good.
• Foods with a high concentration of copper should be avoided, at least in the first year of treatment when the excess copper is being cleared from the body. These foods include liver, nuts, chocolate, mushrooms and shellfish.

Prognosis
If treatment is begun in the early stages of the disease and works very well, one can expect a normal length and quality of life. However without any treatment, Wilson's disease can be fatal before the age of 40. If symptoms develop before treatment has started, some of the symptoms can improve with treatment, but some may remain permanently.

Lifestyle Management
During the initial phase of treatment for Wilson's disease, patients should be advised to avoid the consumption of foods with a high copper content, which are in particular nuts, chocolate, mushrooms, and shellfish and organ meats.  Once therapy is ongoing and the patient is seen to be doing well, a moderate intake of copper is considered to be acceptable. It is also mentioned that, where possible, one should test drinking water obtained from wells for copper content, or use appropriate filters that remove trace elements.  Municipal water supplies do not reportedly usually require analysis. However, patients who have copper pipes in the homes should be advised to flush the system before using water for cooking or when consuming water.

References

1. MEDSCAPE (Emedicine). Wilson disease. Website: http://emedicine.medscape.com
2. PATIENT. Wilson's disease. Website: http://www.patient.co.uk/health/wilsons-disease-leaflet
3. UPTODATE. Wilson disease. Website: https://www.uptodate.com