Wilson 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 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 disease are in a gene called ATP7B. The protein made by this gene is needed in the liver to attach copper to caeruloplasmin and to excrete copper into the bile. If both copies of the gene are faulty, copper builds up in the liver as it can’t be attached to caeruloplasmin or excreted in bile. This leads to a decrease in the caeruloplasmin level in the blood. As the copper levels continue to increase, the liver becomes damaged and the copper spills into the blood. The free (not bound to caeruloplasmin) 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 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 people with Wilson disease. 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 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
Patients with brain involvement may have a range of physical symptoms including
- stiff face muscles
- 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 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.