Wilson Disease
Wilson disease is a rare genetic disorder that prevents the body from properly eliminating excess copper, leading to toxic accumulations that damage the liver, brain, and eyes.
Overview
Wilson disease is an inherited disorder in which excessive amounts of copper accumulate in the body, particularly in the liver, brain, and eyes. The signs and symptoms of the condition usually first appear between the ages of 6 and 45, most frequently beginning during the teenage years. The disorder is characterized by a combination of liver disease alongside neurological and psychiatric problems.
Symptoms and Characteristics
The clinical presentation of Wilson disease varies depending on the organs affected and the age of onset:
Liver Disease
Liver disease is typically the initial feature of Wilson disease in affected children and young adults. Individuals diagnosed at an older age usually do not show symptoms of liver problems, though they may have very mild liver disease. Symptoms include:
- Yellowing of the skin or the whites of the eyes (jaundice)
- Fatigue
- Loss of appetite
- Abdominal swelling
Neurological and Psychiatric Problems
Nervous system or psychiatric issues are often the initial features in individuals diagnosed in adulthood and commonly occur in young adults. These symptoms can include:
- Clumsiness and tremors
- Difficulty walking
- Speech problems
- Impaired thinking ability
- Depression, anxiety, and mood swings
Ocular Features
In many individuals with Wilson disease, copper deposits in the front surface of the eye form a green-to-brownish ring called the Kayser-Fleischer ring, which surrounds the colored part of the eye. Abnormalities in eye movements, such as a restricted ability to gaze upwards, may also occur.
Frequency
Wilson disease is a rare disorder that affects approximately 1 in 30,000 individuals.
Causes
Wilson disease is caused by variants (mutations) in the ATP7B gene. This gene provides instructions for making a protein called copper-transporting ATPase 2, which transports copper from the liver to other parts of the body. While copper is necessary for many cellular functions, it is toxic in excessive amounts. The copper-transporting ATPase 2 protein is crucial for eliminating excess copper from the body.
Variants in the ATP7B gene prevent this transport protein from functioning properly. Without a sufficient shortage of functional protein, excess copper cannot be removed and accumulates to toxic levels, damaging tissues and organs, particularly the liver and brain.
Genetic Modifiers
Research indicates that a normal variation in the PRNP gene may modify the course of Wilson disease. The PRNP gene provides instructions for making prion protein, which is active in the brain and other tissues and appears to be involved in copper transport.
Studies have focused on a PRNP gene variation at position 129 of the prion protein, where individuals can have either the amino acid methionine or valine. Among people with ATP7B gene variants, having methionine instead of valine at this position is associated with a delayed onset of symptoms and an increased occurrence of neurological symptoms, particularly tremors. However, larger studies are needed to firmly establish these effects.
Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.