Wilson’s disease is a rare but serious genetic disorder that disrupts the body’s ability to process copper properly. This essential trace mineral is vital for various physiological processes, including energy production, connective tissue formation, and nervous system function. However, in individuals with Wilson’s disease, copper builds up to toxic levels, primarily affecting the liver and brain. If left untreated, this accumulation can lead to life-threatening complications. This article explores how Wilson’s disease interferes with copper metabolism in the liver and the broader impact on the body.
What Is Wilson’s Disease?
Wilson’s disease, also known as hepatolenticular degeneration, is an autosomal recessive disorder caused by mutations in the ATP7B gene. This gene codes for a protein that helps transport excess copper from the liver into bile, which is then excreted from the body. In individuals with Wilson’s disease, this process is impaired, causing copper to accumulate in the liver over time.
The disease typically manifests between the ages of 5 and 35 but can appear earlier or later. Because the symptoms are highly variable and mimic those of other liver and neurological disorders, Wilson’s disease is often misdiagnosed. Without proper treatment, accumulated copper can spill into the bloodstream, damaging the brain, kidneys, and other organs.
The Role of Copper in the Body
Copper is a trace element necessary for health in small amounts. It plays an essential role in several enzymatic reactions, including:
- Iron metabolism – Copper helps in the absorption and transport of iron.
- Antioxidant defense – It is a cofactor for enzymes like superoxide dismutase, which protect cells from oxidative damage.
- Neurotransmitter synthesis – Copper is involved in dopamine and norepinephrine production.
Normally, dietary copper is absorbed in the small intestine and transported to the liver, where it binds to proteins such as ceruloplasmin. Excess copper is excreted into bile and eliminated via the digestive tract. In Wilson’s disease, this final step—excretion into bile—is disrupted, leading to copper buildup primarily in the liver, followed by secondary deposition in the brain and other organs.
Copper Metabolism and Liver Dysfunction
The liver is the body’s primary site for copper regulation. In Wilson’s disease, the defective ATP7B protein results in copper becoming trapped within liver cells (hepatocytes). Over time, the accumulated copper causes oxidative stress and cell damage, leading to inflammation, fibrosis, and eventually cirrhosis.
Common liver-related symptoms of Wilson’s disease include:
- Hepatitis-like symptoms (fatigue, jaundice, abdominal swelling)
- Hepatomegaly (enlarged liver)
- Elevated liver enzymes (ALT and AST)
- Portal hypertension
- Acute liver failure, especially in young individuals
As hepatocytes become damaged, they can no longer store excess copper effectively. This leads to copper spilling into the bloodstream and being deposited in other tissues, including the brain, eyes, and kidneys. The liver’s declining function exacerbates copper toxicity, creating a vicious cycle of systemic damage.
Neurological and Psychiatric Manifestations
One of the most serious consequences of untreated Wilson’s disease is copper accumulation in the central nervous system. The basal ganglias, a group of nuclei in the brain involved in movement and coordination, are particularly susceptible to copper toxicity.
Neurological symptoms include:
- Tremors and muscle stiffness
- Poor coordination and balance (ataxia)
- Dystonia (involuntary muscle contractions)
- Dysarthria (slurred speech)
In many cases, these symptoms may be mistaken for Parkinson’s disease or other movement disorders, especially in young adults. Psychiatric manifestations are also common and can precede or accompany physical symptoms. These include:
- Depression
- Personality changes
- Irritability
- Cognitive decline
- Psychosis in severe cases
The psychological symptoms can be mistaken for mood disorders, often leading to delays in accurate diagnosis and appropriate treatment.
Diagnosis and Treatment of Wilson’s Disease
Early diagnosis of Wilson’s disease is critical to preventing irreversible damage. A combination of clinical, biochemical, and genetic tests is used to confirm the condition:
- Serum ceruloplasmin – Often low in Wilson’s disease.
- 24-hour urinary copper test – Elevated copper excretion is a key marker.
- Liver biopsy – Direct measurement of hepatic copper concentration.
- Ophthalmologic exam – Detection of Kayser-Fleischer rings, copper deposits in the cornea.
- Genetic testing – Identification of mutations in the ATP7B gene.
Treatment aims to reduce copper accumulation and prevent further damage. The main therapeutic strategies include:
- Medications like penicillamine or trientine bind excess copper and help eliminate it through the urine. These are typically the first-line treatments in symptomatic patients.
With early and consistent treatment, individuals with Wilson’s disease can lead normal, healthy lives. However, lifelong adherence to therapy and regular monitoring are essential.
Prognosis and Long-Term Outlook
The prognosis of Wilson’s disease largely depends on the timing of diagnosis and the effectiveness of treatment. When diagnosed early—before the onset of irreversible liver or brain damage—most patients respond well to therapy and experience significant improvements. However, if left untreated, the disease can be fatal due to liver failure or severe neurological deterioration.
Regular follow-up with a hepatologist or metabolic specialist is crucial for managing the disease. Monitoring includes:
- Liver function tests
- Neurological assessments
- Copper levels in blood and urine
- Adherence to medication and dietary recommendations
Family screening is also recommended, as Wilson’s disease is inherited. Siblings of affected individuals have a 25% chance of having the disease and should be tested, even if asymptomatic.
