What is Wilson Disease?
Wilson disease, also known as hepatolenticular degeneration, is a genetic disorder that causes too much copper to build up in the person’s body. This disease mainly affects the liver and a part of the brain called the basal ganglia, but it can also impact other body systems.
The symptoms of Wilson disease are often linked to the liver and brain. Some liver-related symptoms include vomiting, feeling weak, fluid build-up in the abdomen (ascites), swollen legs, yellowish skin, and itchiness. Brain or neurological symptoms can range from shaking (tremors), muscle stiffness, and difficulty speaking to changes in personality, feelings of anxiety, and hearing or seeing things that aren’t there (auditory or visual hallucinations).
Wilson disease is passed down from parents to their children through genes. Specifically, it’s caused by a mutation in a gene called ATP7B, which is involved in managing copper levels in the body. A person will have the disease if they inherit a copy of this faulty gene from each of their parents.
Diagnosing Wilson disease can be challenging, typically involving a combination of blood tests, urine tests, and a liver biopsy (where a small sample of liver is taken for testing), along with a clinical evaluation of symptoms. Genetic testing might be used to check if family members of a patient have the disease.
The genetic fault in Wilson disease is located on an area of chromosome 13. This mutation affects a gene involved in moving copper in the liver. Most people with Wilson disease start showing liver problems within the first ten years of life. Symptoms related to mental health or behaviour – the “neuropsychiatric features” – usually appear later, around the third or fourth decade of life. Although Wilson disease is rare, it’s important to recognise and treat it, as it can be fatal if not managed.
What Causes Wilson Disease?
Wilson disease is a genetic disorder that results from mutations—specific changes—in a gene known as ATP7B. It sits on chromosome 13, which houses the blueprint for a protein transporter that helps remove excess copper from your body. This transporter is predominantly found in the liver and brain.
Most of the surplus copper in our body (around 95%) gets expelled through the liver. However, if you have Wilson disease, this excretion process doesn’t work properly. As a result, copper starts to gather in the liver and over time, it spills over into the blood. From there, it starts spreading to other parts of the body.
Too much copper in the body can be harmful because it generates harmful substances called free radicals. These free radicals can lead to oxidation—similar to the process that causes metal to rust—of essential proteins and fats within cells. Mitochondria (the cell’s powerhouses), nuclei (the cell’s ‘control room’), and peroxisomes (small parts within a cell that help break down fats and get rid of harmful substances) can be particularly affected by these changes.
Risk Factors and Frequency for Wilson Disease
Wilson disease is a condition that affects 1 out of every 30,000 people, and 1 in every 90 people carry it. Certain communities experience higher rates of Wilson disease due to a higher occurrence of marriages between relatives. The condition affects both men and women equally. Most people get diagnosed between the ages of 4 and 40, but it has been found in children as young as 3 and adults as old as 70.
Signs and Symptoms of Wilson Disease
Wilson disease is a condition that is passed down through families, and some patients might have a family member who also has the disease. It can cause a variety of symptoms such as stomach pain, yellowing of the skin (jaundice), feelings of weakness, shifts in personality, depression, headaches, sleeping difficulties, seizures, and unusual body movements (chorea and hemiballismus).
Between 30% to 50% of patients may also experience symptoms related to mental health and movement, such as unsteady shaking (asymmetrical tremor), drooling, difficulty with coordination (ataxia), a mask-like expression, or clumsiness.
During a physical exam, doctors may notice an enlarged liver or spleen, which are signs of Wilson disease. If the disease has advanced to cirrhosis, signs of long-term liver disease may be more noticeable. Eye examinations might show yellowing of the eyes (icterus) or copper-coloured rings on the cornea known as Kayser-Fleischer rings. Other signs of Wilson disease include difficulty speaking, stiffness in muscles, and a bluish color at the base of the fingernails (lunulae ceruleae).
Bone problems are also quite common and it can look like early-onset osteoarthritis, often affecting the central skeleton and spine. Also, about 10-15% of patients experience a type of anemia due to the breakdown of red blood cells caused by high copper concentration.
Lastly, patients may also have kidney symptoms, similar to Fanconi syndrome or formation of stones in the urinary tract (urolithiasis).
Here’s a simplified list of potential symptoms:
- Stomach pain
- Yellowing of the skin (jaundice)
- Feelings of weakness
- Changes in personality
- Depression
- Headaches
- Sleeping difficulties
- Seizures
- Unusual body movements (chorea and hemiballismus)
- Unsteady shaking (asymmetrical tremor)
- Drooling
- Difficulty with coordination (ataxia)
- A mask-like expression
- Clumsiness
- Enlarged liver or spleen
- Signs of long-term liver disease (if the disease has advanced to cirrhosis)
- Yellow eyes (icterus) or copper-coloured rings on the cornea (Kayser-Fleischer rings)
- Difficulty speaking and stiffness in muscles
- Bluish color at the base of the fingernails (lunulae ceruleae)
- Bone problems resembling early-onset osteoarthritis
- Anemia caused by breakdown of red blood cells (seen in 10-15% of patients)
- Kidney problems, similar to Fanconi syndrome or urolithiasis
Testing for Wilson Disease
If you’re experiencing symptoms consistent with a condition known as Wilson’s disease, or have a family member previously diagnosed with the condition, your doctor may order a series of tests to confirm a diagnosis. A key indication of Wilson’s disease is unusually low levels of a protein called ceruloplasmin, usually less than 20 mg/dL, which is found in your blood. Normally, the levels of this protein range between 20 to 40 mg/dL.
Another sign of Wilson’s disease is high levels of copper in your urine, often exceeding 100 mcg/dL. Coupling these two lab findings with a physical examination result referred to as Kayser-Fleischer rings (copper-colored rings around your eyes), can usually confirm the diagnosis.
However, if your doctor is uncertain or suspects another underlying condition, they may order a liver biopsy. This is the most accurate test to determine whether or not you have Wilson’s disease. A positive result here would be a copper level greater than 250 mcg/g in the liver tissue.
In addition, your doctor may order an MRI scan to check for any possible impact of the disease on your brain. Normal functioning of your liver might also be disturbed, indicated by elevated levels of AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) enzymes in your blood.
If Wilson’s disease has caused significant liver damage, certain other signs will be present. For example, your albumin levels might be low, because damaged liver cells can’t produce this protein properly. Your prothrombin time, which is a measure of how quickly your blood clots, could be longer than normal due to lack of clotting factors produced by your liver. Also, alkaline phosphatase levels might be low in cases of Wilson-related acute liver failure.
If you’re experiencing neurological symptoms, an MRI of the brain might reveal certain patterns that suggest the presence of Wilson’s disease. An electrocardiogram (ECG) might also be performed to check for certain anomalies, such as an enlarged heart (ventricular hypertrophy), abnormal heart rhythms (arrhythmias), and changes in your heart’s electrical activity.
While there is no completely foolproof test for Wilson’s disease, tests measuring ceruloplasmin, copper levels in your blood, and urinary copper excretion in a 24-hour window can provide a good estimate of the amount of copper in your body. Throughout this process, it’s paramount that your immediate family members also get screened for the disease.
Treatment Options for Wilson Disease
The primary treatment for Wilson disease involves using medication that helps remove excess copper from the body, a process known as chelation therapy. Preferred medicines include penicillamine and trientine, with trientine often preferred due to fewer side effects. Another treatment option includes oral zinc supplements, which help reduce copper absorption in the body.
It’s important to understand that long-term chelation therapy can sometimes worsen symptoms. However, the use of D-penicillamine is considered safe during pregnancy, and it does not harm the fetus.
If Wilson disease progresses to the point where it causes liver cirrhosis (severe scarring of the liver) and related complications, specific procedures can be performed. One is called a Transjugular Intrahepatic Portosystemic Shunt (TIPS), which can help manage recurrent variceal bleeding (bleeding from enlarged veins in the esophagus or stomach). In some cases, a liver transplant may be needed, which can actually cure Wilson disease.
For muscle stiffness, spasms, and symptoms similar to Parkinson’s disease, medications such as baclofen, anticholinergics (like trihexyphenidyl), GABA antagonists, and levodopa can be beneficial.
It’s also been noticed that a liver transplant has been helpful in improving neurological dysfunction in some patients who were not responding well enough to medical therapy.
In terms of diet, it’s suggested to eat foods low in copper. This means avoiding foods like mushrooms, chocolate, nuts, dried fruit, liver, and shellfish, which are known to contain high levels of copper.
Physiotherapy and occupational therapy can also be beneficial especially for those with neurological symptoms due to the disease. These therapies can be useful in managing symptoms like ataxia (loss of control of body movements), dystonia (involuntary muscle contractions), and tremors. They can prevent contractures (permanent shortening of a muscle or joint) that can occur as a result of dystonia. The copper-removal treatment can take up to six months to start working, so these therapies can assist in coping with symptoms during this period.
What else can Wilson Disease be?
When doctors are trying to identify a particular health issue, they have to consider other conditions that might be causing similar symptoms. This process is called differential diagnosis. The diseases that might possibly lead to similar symptoms include:
- Chronic active hepatitis (a long-term liver disease),
- Hemolytic anemias (a group of conditions in which red blood cells are destroyed faster than the body can replace them).
Similarly, certain neuropsychiatric disorders can show up with similar symptoms and may be mistaken for other conditions. These include:
- Various types of Parkinsonian syndromes (neurological disorders that cause movement problems),
- Pantothenate kinase deficiency associated neurodegeneration (a disorder characterized by iron accumulation in the brain),
- Neuroacanthocytosis syndromes (rare disorders that affect brain and muscle functions),
- Huntington’s disease (a genetic disorder that causes progressive brain damage).
All mentioned conditions might present with personality changes, stiff muscles, abnormal, often painfully sustained, body postures and movement disorders.
What to expect with Wilson Disease
Different rating methods have been developed to predict the outcome of certain health conditions. These methods often take into consideration various factors like the amount of AST (an enzyme found in high amounts in the liver), bilirubin (a waste product in your blood), and prothrombin time (a test that measures how long it takes for your blood to clot).
Patients who have a score of 7 or above in this rating system should be considered for a liver transplant. Without treatment, people in this category are generally not expected to live more than 8 weeks. However, after undergoing a liver transplant, the chances of a good outcome are quite high. For instance, studies have shown a survival rate of 87% 15 years after the transplant.
Possible Complications When Diagnosed with Wilson Disease
Possible Consequences:
- Damage of Liver
- Mental conditions caused by brain damage
- Enlarged spleen
- Accumulation of fluids in the abdomen
- Bleeding of enlarged veins
- Kidney failure due to severe liver disease
- Mental and behavioral changes due to liver failure
- Severe complications with a potential risk of death
Recovery from Wilson Disease
It’s important to keep a close eye on your health when you have high levels of copper in your urine or blood. Doctors will often conduct regular checks every 4-8 weeks to measure the levels of copper in your urine, as well as run tests to monitor your blood, kidney, and liver health. They’ll also look at your eyes during these check-ups. Most people in this situation will need ongoing treatment to remove the excess copper from their bodies, a therapy known as chelation therapy. Furthermore, they should avoid alcohol and any medicines that can harm the liver.
