Wilson's Disease
Wilson’s disease is an inherited condition associated with abnormal copper metabolism that results in excess storage of copper, primarily in the liver and brain. Copper is an essential mineral that is absorbed into the body through diet. It is incorporated into enzymes that play a role in the regulation of iron metabolism, formation of connective tissue, energy production at the cellular level, the production of melanin, and the function of the nervous system 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 excreted into the into the bile and removed from the body in the stool. Normally, about 95% of the copper found in the blood is contained in caeruloplasmin. This enzyme, which plays a role in iron metabolism in the body, is formed in the liver.
Wilson's disease is an autosomal recessive disorder ie it takes two altered gene copies, one from each parent, to cause the disorder. Those with only one copy are carriers and can pass the mutation on to their children but do not have symptoms of the disease. The gene mutation in Wilson’s disease is in a gene called ATP7B. This gene is needed both to attach copper to the developing caeruloplasmin molecule and to excrete copper. 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 build-up becomes toxic, copper begins to damage the cells and tissues in the liver, spills into the blood, and forms deposits in other organs such as the brain and kidneys. Free (unbound) copper concentrations in the blood increase and can cause oxidative damage to cells. Affected patients may have signs and symptoms associated with the liver dysfunction, neurological damage, or both. The severity of the condition depends partly upon the gene mutations present.
About 1 in 30,000 people in the population have Wilson’s disease and as many as 1 in 90 are estimated to be carriers. There are currently over 40 known mutations of the ATP7B gene that have been associated with Wilson’s disease. Only a few of these mutations are common, however, with their prevalence varying with ethnicity throughout the world. Affected patients may have two copies of the same genetic mutation or two different mutations.
Wilson’s disease patients with liver involvement typically 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
- dystonia
- 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.
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.
