GeneHealth - Your precision medicine

Wilson Disease

Disease Details

Family Health Simplified

Buy Membership

Description: Wilson disease is a genetic disorder that leads to excessive accumulation of copper in the liver, brain, and other vital organs, causing neurological and hepatic symptoms.
Type: Wilson disease is an autosomal recessive disorder.
Signs And Symptoms: The main sites of copper accumulation are the liver and the brain, and consequently liver disease and neuropsychiatric symptoms are the main features that lead to diagnosis. People with liver problems tend to come for medical attention earlier, generally as children or teenagers, than those with neurological and psychiatric symptoms, who tend to be in their 20s or older. Some are identified only because relatives have been diagnosed with Wilson's disease; many of these, when tested, turn out to have been experiencing symptoms of the condition, but have not received a diagnosis.
Prognosis: Left untreated, Wilson's disease tends to become progressively worse and is eventually fatal. Serious complications include liver cirrhosis, acute kidney failure, and psychosis. Liver cancer and cholangiocarcinoma may occur, but at a lower incidence than other chronic liver diseases, and the risk is greatly reduced with treatment. With early detection and treatment, most of those affected can live relatively normal lives and have a life expectancy close to that of the general population. Liver and neurologic damage that occurs prior to treatment may improve, but it is often permanent. Fertility is usually normal and pregnancy complications are not increased in those with Wilson's disease that is treated.
Onset: Wilson disease typically has an onset in late childhood or early adulthood, usually between the ages of 5 and 35. Symptoms can vary widely, but they often include liver disease, neurological symptoms, and psychiatric disturbances. Early diagnosis and treatment are crucial to managing the symptoms and preventing serious complications.
Prevalence: Wilson disease is a rare genetic disorder. The prevalence is estimated to be about 1 in 30,000 to 1 in 40,000 individuals worldwide.
Epidemiology: Wilson disease is a rare inherited disorder characterized by excessive accumulation of copper in the body. Its epidemiology reveals the following key points:

- Prevalence: The disease occurs in approximately 1 in 30,000 to 1 in 100,000 people worldwide.
- Genetics: It is an autosomal recessive disorder caused by mutations in the ATP7B gene.
- Demographics: Both males and females are equally affected, and it manifests typically between the ages of 5 and 35, although it can occur at any age.
- Geographic Distribution: The disease has been documented globally, with certain populations, such as those of Eastern European, Sicilian, and Sardinian descent, showing higher carrier rates.

Specific statistics and detailed population studies can further elaborate on the nuanced epidemiological characteristics within different regions and demographics.
Intractability: Wilson disease is not intractable. With early diagnosis and proper treatment, individuals can manage the condition effectively. The mainstay treatments include chelation therapy to remove excess copper and zinc therapy to prevent copper absorption. Lifelong adherence to treatment and dietary modifications can help manage symptoms and prevent significant complications.
Disease Severity: Wilson disease is a genetic disorder characterized by excessive accumulation of copper in the body, particularly in the liver, brain, and other vital organs. The severity of the disease can vary widely among individuals. Some may remain asymptomatic for years, while others can experience severe symptoms including liver dysfunction, neurological issues, and psychiatric disturbances. Early diagnosis and treatment are crucial to managing the disease effectively and preventing serious complications.
Healthcare Professionals: Disease Ontology ID - DOID:893
Pathophysiology: Copper is needed by the body for a number of functions, predominantly as a cofactor for a number of enzymes such as ceruloplasmin, cytochrome c oxidase, dopamine β-hydroxylase, superoxide dismutase, and tyrosinase.Copper enters the body through the digestive tract. A transporter protein on the cells of the small bowel, copper membrane transporter 1 (Ctr1; SLC31A1), carries copper inside the cells, where some is bound to metallothionein and part is carried by ATOX1 to an organelle known as the trans-Golgi network. Here, in response to rising concentrations of copper, an enzyme called ATP7A (Menkes' protein) releases copper into the portal vein to the liver. Liver cells also carry the CMT1 protein, and metallothionein and ATOX1 bind it inside the cell, but here, ATP7B links copper to ceruloplasmin and releases it into the bloodstream, as well as removing excess copper by secreting it into bile. Both functions of ATP7B are impaired in Wilson's disease. Copper accumulates in the liver tissue; ceruloplasmin is still secreted, but in a form that lacks copper (termed apo-ceruloplasmin) and is rapidly degraded in the bloodstream.When the amount of copper in the liver overwhelms the proteins that normally bind it, it causes oxidative damage through a process known as Fenton chemistry; this damage eventually leads to chronic active hepatitis, fibrosis (deposition of connective tissue), and cirrhosis. The liver also releases copper into the bloodstream that is not bound to ceruloplasmin. This free copper precipitates throughout the body, but particularly in the kidneys, eyes, and brain. In the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus (together called the lenticular nucleus); these areas normally participate in the coordination of movement and play a significant role in neurocognitive processes such as the processing of stimuli and mood regulation. Damage to these areas, again by Fenton chemistry, produces the neuropsychiatric symptoms seen in Wilson's disease.Why Wilson's disease causes hemolysis is unclear, but various lines of evidence suggest that a high level of free (nonceruloplasmin-bound) copper has a direct effect on either oxidation of hemoglobin, inhibition of energy-supplying enzymes in the red blood cell, or direct damage to cell membranes.
Carrier Status: In Wilson disease, carrier status refers to individuals who possess one mutated copy of the ATP7B gene and one normal copy. These carriers generally do not exhibit symptoms of the disease. Wilson disease is inherited in an autosomal recessive manner, meaning that a person must inherit two mutated copies of the ATP7B gene (one from each parent) to manifest the disease. Carriers, therefore, have a reduced risk of passing the disease to their offspring but can still pass on the mutated gene.
Mechanism: Wilson disease is a genetic disorder characterized by excessive accumulation of copper in the body, particularly in the liver, brain, and other vital organs. This condition is caused by mutations in the ATP7B gene, which encodes a protein responsible for transporting copper out of cells and into bile for excretion.

**Mechanism:**

- The ATP7B gene is crucial for copper homeostasis.
- Mutations in ATP7B disrupt the normal function of this protein.
- Impaired ATP7B function leads to defective copper transport.
- Consequently, copper accumulates in hepatocytes (liver cells).
- Excess copper in the liver causes cellular damage and, eventually, liver disease.
- Over time, copper is released into the bloodstream and deposited in other organs, including the brain, kidneys, and corneas.

**Molecular Mechanisms:**

1. **Copper Transport Disruption:**
- ATP7B normally binds copper and transports it into the Golgi apparatus for incorporation into copper-dependent enzymes or directs it to the bile for excretion.
- Mutations impede this transport, leading to insufficient copper incorporation into ceruloplasmin and inadequate excretion into bile.

2. **Cellular Damage:**
- The copper accumulation generates reactive oxygen species (ROS), which cause oxidative stress and damage to cellular components like proteins, lipids, and DNA.
- Chronic oxidative stress leads to cell dysfunction, apoptosis, and liver fibrosis.

3. **Neurotoxicity:**
- When copper spills over into the bloodstream, it can cross the blood-brain barrier and accumulate in various brain regions.
- This accumulation interferes with neural function, causing neuropsychiatric and motor symptoms.

Understanding these molecular mechanisms helps in diagnosing and developing treatments for Wilson disease, such as chelating agents that bind copper and promote its excretion.
Treatment: Wilson disease is a genetic disorder that leads to excessive accumulation of copper in the body. Treatment often includes:

1. **Chelating Agents**: Medications such as penicillamine or trientine that help remove excess copper by binding to it and facilitating its excretion through urine.

2. **Zinc Therapy**: Zinc acetate is used to block the absorption of copper from the digestive tract.

3. **Dietary Changes**: Avoiding foods high in copper, such as shellfish, nuts, and chocolate, to help reduce copper intake.

4. **Liver Transplant**: In severe cases where there is significant liver damage or liver failure, a liver transplant may be necessary.

Patients need ongoing monitoring and treatment adjustments to manage copper levels effectively.
Compassionate Use Treatment: Compassionate use treatments for Wilson disease typically refer to providing access to investigational drugs or therapies that have not yet been approved by regulatory agencies. These treatments are often considered when standard treatments are ineffective or not suitable for the patient.

Off-label or experimental treatments for Wilson disease may include:
1. **Tetrathiomolybdate** - This is a copper-chelating agent that has been studied for its effectiveness in Wilson disease but is not yet widely approved for this indication.
2. **Zinc Acetate** - Although zinc salts are FDA-approved for maintenance therapy, some practitioners might use different formulations or dosing regimens off-label.
3. **Liver Transplantation** - In severe cases of Wilson disease where hepatic function is critically compromised and unresponsive to medical therapy, liver transplantation can be considered a life-saving measure.
4. **Investigational Therapies** - Ongoing clinical trials are exploring various new drug candidates and gene therapies aimed at better managing or potentially curing Wilson disease.

Patients should consult their healthcare provider to discuss potential treatment options, including compassionate use and off-label treatments, to determine the best course of action based on their specific condition.
Lifestyle Recommendations: For Wilson disease, lifestyle recommendations include:

1. **Dietary Adjustments**: Reduce copper intake. Avoid foods high in copper, such as shellfish, liver, mushrooms, nuts, chocolate, and certain beans.
2. **Regular Monitoring**: Keep regular check-ups with your healthcare provider to monitor copper levels and liver function.
3. **Medication Adherence**: Take prescribed medications, such as chelating agents (penicillamine, trientine) or zinc, consistently to manage copper levels.
4. **Avoid Alcohol**: Alcohol can exacerbate liver damage, so it is generally advised to avoid it.
5. **Safe Water Sources**: Use distilled or demineralized water if you have high levels of copper in your tap water.
6. **Regular Exercise**: Engage in moderate physical activity to maintain overall health, but avoid excessive or strenuous exercise which can stress the liver.
7. **Family Screening**: Ensure that family members get screened for Wilson disease, as it is a hereditary condition.

Always consult with a healthcare provider for personalized advice.
Medication: Medical treatments are available for Wilson's disease. Some increase the removal of copper from the body, while others prevent the absorption of copper from the diet.
Generally, penicillamine is the first treatment used. This binds copper (chelation) and leads to excretion of copper in the urine. Hence, monitoring of the amount of copper in the urine can be done to ensure a sufficiently high dose is taken. Penicillamine is not without problems; about 20% experience a side effect or complication of penicillamine treatment, such as drug-induced lupus (causing joint pains and a skin rash) or myasthenia (a nerve condition leading to muscle weakness). In those who presented with neurological symptoms, almost half experience a paradoxical worsening in their symptoms. While this phenomenon is observed in other treatments for Wilson's, it is usually taken as an indication for discontinuing penicillamine and commencing second-line treatment. Those intolerant to penicillamine may instead be commenced on trientine hydrochloride, which also has chelating properties. Some recommend trientine as first-line treatment, but experience with penicillamine is more extensive. A further agent, under clinical investigation by Wilson Therapeutics, with known activity in Wilson's disease is tetrathiomolybdate. This is regarded as experimental, though some studies have shown a beneficial effect.Once all results have returned to normal, zinc (usually in the form of a zinc acetate prescription called Galzin) may be used instead of chelators to maintain stable copper levels in the body. Zinc stimulates metallothionein, a protein in gut cells that binds copper and prevents its absorption and transport to the liver. Zinc therapy is continued unless symptoms recur or if the urinary excretion of copper increases.In rare cases where none of the oral treatments is effective, especially in severe neurological disease, dimercaprol (British anti-Lewisite) is occasionally necessary. This treatment is injected intramuscularly (into a muscle) every few weeks and has unpleasant side effects such as pain.People who are asymptomatic (for instance, those diagnosed through family screening or only as a result of abnormal test results) are generally treated, as the copper accumulation may cause long-term damage in the future. Whether these people are best treated with penicillamine or zinc acetate is unclear.
Repurposable Drugs: Wilson disease is a genetic disorder in which excess copper builds up in the body. To manage this condition, certain drugs originally intended for other uses have shown potential. These repurposable drugs include:

1. **Tetrathiomolybdate**: Investigated for its copper-chelating properties.
2. **N-acetylcysteine (NAC)**: Exhibits antioxidant properties that may offer therapeutic benefits.
3. **Trientine analogs**: Originally developed for conditions like rheumatoid arthritis, they have shown promise in copper chelation.

These drugs could offer additional treatment options alongside conventional therapies such as penicillamine and zinc acetate.
Metabolites: Wilson disease is a genetic disorder that results in excessive accumulation of copper in the body. Some key metabolites associated with Wilson disease include:

1. **Copper**: Elevated levels in tissues, primarily in the liver, brain, and eyes.
2. **Ceruloplasmin**: Typically low levels in the blood, as it is a copper-carrying protein.
3. **Free (non-ceruloplasmin-bound) copper**: Elevated in the blood due to poor incorporation into ceruloplasmin.
4. **Urinary Copper**: Increased excretion of copper in urine.

No information was found specifically related to nan for this context. If nan involves a specific biochemical concept or abbreviation, please provide more details.
Nutraceuticals: In the context of Wilson disease, which is a genetic disorder resulting in excessive accumulation of copper in the body, there is limited evidence supporting the use of nutraceuticals (dietary supplements or herbal products) as a primary treatment. Treatment typically involves chelating agents like penicillamine or trientine, which help remove excess copper from the body, and zinc acetate, which prevents copper absorption.

Research into nanotechnology (nan) for Wilson disease is still in its early stages. Potential future applications may involve targeted drug delivery systems to improve the efficiency of copper chelation or develop novel therapies aimed at more precisely targeting the underlying genetic abnormalities. However, these approaches are not yet standard treatment options.
Peptides: Wilson disease is a genetic disorder that leads to excessive accumulation of copper in the body. The context of "peptides" and "nan" in relation to Wilson disease is unclear. Peptides generally refer to short chains of amino acids, which are not directly relevant to the typical discussion of Wilson disease. "Nan" might refer to "nanotechnology," which involves the use of nanomaterials and nanodevices but doesn’t have a direct established application in the treatment or diagnosis of Wilson disease at this time. Research in medical nanotechnology is ongoing and could potentially contribute to innovative diagnostics or treatments in the future.