Wilson's disease is a rare inherited disorder that is characterized by the accumulation of copper in the body. It is caused by mutations in the ATP7B gene which encodes a protein that plays an important role in the transport of copper from the liver to the rest of the body. It also helps remove excess copper from the body.
Although the accumulation of copper begins at birth, symptoms of the disorder do not appear until later in life, between the ages of 6 and 40. Liver disease is the most common manifestation of Wilson’s disease. Involvement of the nervous system or psychiatric changes result in symptoms like tremor, muscle stiffness, drooling, difficulty with speech, physical coordination, abrupt personality change, inexplicable deterioration at school or other work, neurosis, and psychosis.
For diagnosis, healthcare professionals typically look at a person’s medical history, symptoms, physical exam, characteristic features like Kayser-Fleischer ring(a deep copper-colored ring around the edge of the cornea that represents copper deposits in the eye) and laboratory tests.
Prognosis for patients with Wilson disease is usually good, unless disease is advanced before treatment begins. Affected people require lifelong treatment, which may include certain medications and dietary modifications. If treatment is begun early enough, symptomatic recovery is usually complete, and a life of normal length and quality can be expected.
Wilson's disease is present at birth, but signs and symptoms don't appear until the copper builds up in the brain, liver, or another organ. A few signs and symptoms depend on the parts of the body affected by the disease. These include
In Wilson's disease, the majority of patient’s present with hepatic symptoms at diagnosis, and almost all have signs of liver damage over the course of the disease.
In some cases, people develop these symptoms when they have acute liver failure. These symptoms may include:
Nausea and vomiting
Poor appetite
Darkened color of urine
Yellowish tint to the whites of the eyes and skin, called jaundice
Pain in the upper part of the abdomen
In some people the symptoms of the disease develop in case of chronic liver disease and complications from cirrhosis. The clinical features of cirrhosis include spider naevi, splenomegaly, portal hypertension, and ascites.
It has been recommended that all young patients with unexplained chronic liver disease, with or without cirrhosis, should be screened for Wilson’s disease if the following symptoms are visible in them:
Swelling of the lower legs, ankles, or feet, called edema
Itchy skin
Feeling tired
Neurological and neuropsychiatric signs are present in 40–50% of patients with Wilson’s disease. A few signs may appear before the characteristic neurological features, including changes in behavior, deterioration of school work, or an inability to carry out activities that need good hand-eye coordination. Common neurological symptoms may include:
Tremors (unintentional and uncontrollable rhythmic movement of one part or one limb of your body)
Lack of motor coordination
Drooling of saliva
Slurred or slow speech
Dystonia (contraction of muscles involuntarily, causing repetitive or twisting movements)
Seizures
Along with behavioral changes, other psychiatric manifestations include
Hallucinations and delusions
Suicidal tendencies
It is a severe mental disorder in which thought and emotions are impaired and contact is lost with external reality. Psychosis is majorly seen in patients with a neurological Wilson’s disease manifestation.
The main ophthalmic findings of Wilson’s disease include:
K-F (Kayser-Fleischer rings) - usually greenish, gold, or brownish rings around the edge of the corneas
Sunflower cataracts - brilliantly multicolored and are visible only by slit-lamp examination)
Other less common symptoms include
Night blindness
Exotropic strabismus - a form of eye misalignment in which one or both of the eyes turn outward
Optic neuritis - characterized by inflammation of the optic nerve, which carries visual information from the eye to the brain. This inflammation usually causes temporary vision loss.
Optic disc pallor - refers to an abnormal pale yellow coloration of the optic disc
Pathological changes of bone have been recorded to account for osteomalacia, osteoporosis, spontaneous fractures, adult rickets, and osteoarthritis.
Copper accumulation in heart tissues can cause cardiomyopathy and arrhythmias.
Other rare manifestations include hypoparathyroidism, infertility, repeated miscarriages, and kidney abnormalities.
Wilson's disease is caused by changes (mutations) in the ATP7B gene. This gene encodes a protein that plays an important role in the transport of copper from the liver to the rest of the body. Mutations in the ATP7B gene prevent this protein from working properly, which can lead to an accumulation of copper in the body.
The ATP7B mutations that cause Wilson's disease are inherited, ie. they are passed from parent to child. These mutations are autosomal recessive, meaning that a person must inherit two ATP7B genes with mutations, one from each parent, to have Wilson disease.
People who have one ATP7B gene without a mutation and one ATP7B gene with a mutation do not have Wilson disease, but they are carriers of the disease.
The risk of Wilson’s disease is genetic ie. it is inherited and the risk increases if your parents or siblings have the condition. A genetic test can be performed if a child shows symptoms of Wilson’s and has one or both parents who have the disease.
There is no one test for the diagnosis of Wilson’s disease. The diagnostic challenge is that the symptoms are often nonspecific and the disease affects many different organ systems, which results in confusion with other disorders. Many symptoms may evolve over time rather than appear all at once.
In a few cases, the diagnosis is easy to establish in individuals with neurological symptoms, K-F rings, and a low ceruloplasmin concentration. Doctors diagnose Wilson's disease based on your medical and family history, a physical exam, an eye exam, and tests.
A doctor will ask about the family and personal medical history of Wilson's disease and other conditions that could be causing the symptoms.
During a physical exam, the doctor will look for physical signs related to Wilson’s disease.
Using a microscope with a high-intensity light source (slit lamp), an ophthalmologist checks the eye for Kayser-Fleischer rings, which are caused by excess copper in the eyes. Wilson's disease also is associated with a sunflower cataract, that can be seen on an eye exam.
The doctor may order one or more blood tests, including tests that check amounts of:
Liver biochemistry: People with Wilson's disease may have abnormal alanine transaminase (ALT) and aspartate transaminase (AST) levels.
Ceruloplasmin: This protein is the major carrier of copper in the blood circulation carrying six copper atoms per molecule of ceruloplasmin. A ceruloplasmin concentration of less than 0·2 g/L (normal laboratory range 0·2 to 0·5 g/L), is regarded to be consistent with Wilson’s disease.
Infants should not be tested until after age 1 year because ceruloplasmin levels are low during the first few months of life. Children < 6 years with normal test results should be retested 5 to 10 years later.
Copper levels: The normal copper content of the liver is less than 55 μg/g. The hepatic copper content ⩾of 250 μg/g dry weight is considered the hallmark of Wilson’s disease. It is the method of choice for confirming the diagnosis of the disease. Hepatic copper concentration should be obtained in cases where the diagnosis is not straightforward and in younger patients.
A 24-hour urinary copper excretion is increased in Wilson’s disease, which reflects the amount of serum-free copper in circulation.
In people symptomatic of Wilson’s disease, a urinary copper excretion in a 24-hour period of >1.6 μmol (>100 μg/24 h) is considered diagnostic of the disease.
The reference limits for normal 24-h excretion of copper vary between laboratories, with many taking 40 μg per 24 h (0·6 μmol/24 h) as the upper limit of normal.
Liver biopsy is an important tool for the evaluation of patients with the hepatic disease if the results of blood and urine tests don’t confirm or rule out a diagnosis of Wilson disease. During a liver biopsy, the doctor evaluates small pieces of tissue from your liver. A pathologist will examine the tissue under a microscope to look for features of specific liver diseases, such as Wilson's disease, and check for liver damage and cirrhosis.
All first-degree relatives of a patient with newly diagnosed Wilson’s disease must be screened for Wilson’s disease. Molecular genetic analysis can be useful for families where both mutations have been identified in the index patient, enabling molecular analysis for the same mutation in the family members.
Neurologic evaluation and radiologic imaging of the brain, should be considered prior to treatment in all patients with neurologic Wilson’s disease and should be part of the evaluation of any patient presenting with neurological symptoms:
Magnetic resonance imaging (MRI): MRI is a non-invasive imaging technology that produces three dimensional detailed anatomical images. MRI of the brain appears to be more sensitive than CT (Computed Tomography) scanning in detecting early lesions of Wilson disease.
Computed tomography (CT): A CT scan of the head is an imaging scan that uses X-rays to develop a 3D image of the skull, brain, and other related areas of the head.
Wilson’s disease is a genetic disorder. People with a family history of Wilson’s disease should always go for genetic counseling as a part of pregnancy planning. Genetic counseling is a way to estimate personal genetic risk information and translate it into practical information for families. Genetic counseling helps families understand information about genetic disorders and explain the patterns of inheritance. Therefore, people will get a better insight into the future.
A general practitioner can evaluate the symptoms, and start the treatment. They can further refer to other doctors for assessment depending upon the organ affected.
Hepatologists: They specialize in the diagnosis and treatment of diseases related to the liver, the biliary duct, the gallbladder, and the pancreas.
Gastroenterologists: They specialize in the digestive system and its disorders.
If you are facing any health issue, consult our healthcare professionals.
Successful treatment of Wilson’s disease depends upon timing more than medication. Treatment often happens in stages and should last a lifetime. If a person stops taking the required medications, copper can build back up again. Compliance is a problem for patients because they find it difficult to take life-long treatment when they feel healthy. The various treatment modalities are discussed in detail:
The first treatment is to remove excess copper from the body through chelation. Penicillamine and trientine are chelating agents used to treat Wilson's disease. These medicines work by binding excess copper in body tissues, carrying it to the kidneys where it is finally removed via urine.
Penicillamine: Penicillamine is the most commonly used chelating medication but while taking this medication, it is advisable to have regular monitoring of full blood count and urinary protein because of possible adverse effects. The early side effects in the first 1–3 weeks include sensitivity reactions with fever, rash, swelling of lymph nodes, thrombocytopenia, and increased levels of protein in urine. These side effects of penicillamine can be severe, requiring discontinuation in many patients.
Trientine hydrochloride: It is regarded as an accepted alternative to penicillamine for the initial treatment of Wilson’s disease. Trientine has few side effects and although they are similar to penicillamine, the frequency is much lower.
The second stage is to maintain normal levels of copper after removal. The doctor may prescribe zinc or ammonium tetrathiomolybdate as it prevents the intestines from absorbing copper.
Ammonium tetrathiomolybdate: this medication forms a complex with copper and protein. When it is taken with meals, the drug forms complexes with copper in the food and that is secreted into the intestine, thus preventing absorption.
Zinc acetate: Zinc was first used in the 1960s to treat Wilson’s disease. Its mode of action is through inhibition of copper absorption in the intestine. Zinc monotherapy appears to be effective and safe in neurologic Wilson’s disease and consequently may have a role as first-line therapy in this setting.
NOTE: Penicillamine or trientine must not be taken at the same time as zinc because either drug can bind with zinc, forming a compound with no therapeutic effect.
After the symptoms improve and the copper levels are normal, doctors usually focus on long-term maintenance therapy. This includes continuing zinc or chelating therapy and regularly monitoring your copper levels. Even avoiding foods having a high level of copper in them such as dried fruits, mushrooms, nuts, chocolate, shellfish, and multivitamin.
Toxic concentrations of copper in the liver produce oxidant damage to mitochondria with lipid peroxidation, which can be reduced experimentally by vitamin E administration. Vitamin E concentrations may be low in patients with Wilson’s disease.
Liver transplantation may be lifesaving for patients with severe Wilson’s disease or severe hepatic insufficiency non responsive to drugs. Liver transplantation is a curative therapy, with neurologic and psychiatric disease stabilizing or improving, and Kayser-Fleischer rings disappearing over time.
Milk thistle: It is a natural remedy that can help reduce the risk of liver failure if a person has Wilson’s disease. This strong antioxidant has been found to help regenerate injured liver cells and halt the development of cirrhosis in those who have inflammatory liver conditions. It may even improve liver function and survival in those who do have cirrhosis.
Turmeric: Turmeric contains a compound called curcumin which has potent antioxidant properties, it also works as a copper chelating agent.
Vitamin E: It can be useful as an adjunctive treatment for those with Wilson’s disease. Oxidative stress has been found to play a critical role in Wilson’s disease and vitamin E may be able to counter this.
Zinc supplements: Zinc salts can hamper the absorption of copper in your digestive tract and help reduce the buildup of copper in the body.
Follow a low copper diet: A low copper diet is an important part of managing this condition. Avoid foods with a high copper content such as mushrooms, chocolate, nuts, dried fruits like prunes, dates, and raisins, soy products, shellfish, and organ meat initially.
Ayurvedic regimen: The ancient science of Ayurveda classifies Wilson’s disease as a liver disease dominated by pitta. Treatment, therefore, focuses on regulating pitta, expelling toxins (ama) from the body, boosting the digestive fire (Agni), and detoxifying and protecting the liver.
Medicines that expel copper: This is the first line of treatment for Wilson’s disease, aimed at controlling the amount of copper that builds up in the body. The medicines that release copper from the organs into your bloodstream.
Self-care is an integral part of daily life. It means you take responsibility for your health and well-being, with support from people involved in your care. Self-care involves things to stay fit, maintain good mental and physical health and effectively deal with other minor ailments.
Foods with a high concentration of copper generally should be avoided, at least in the first year of treatment when the excess copper is being cleared from the body. These include liver, cashews, black-eyed peas, vegetable juice, shellfish, mushrooms, chocolate and cocoa.
Poor long-term adherence to drug therapy for Wilson’s disease is common. But, continual, lifelong treatment of Wilson disease is mandatory regardless of whether symptoms are present. Regular follow-up care with an expert in liver disease is highly recommended.
Cirrhosis of the liver is one of the potential complications that may develop from Wilson's disease. As the patient's body attempts to clear the buildup of excess copper from the liver, scar tissue is formed in the area, compromising normal liver function.
During the early stages of cirrhosis, patients may be asymptomatic, with symptoms appearing only in the most advanced stages. In the later stages, the symptoms of cirrhosis include jaundice, itchy skin, fatigue, swelling in the legs, and loss of appetite. For patients with Wilson's disease, liver abnormalities can begin as early as six years of age.
Patients with Wilson's disease have an increased risk of developing kidney stones, which are formed from tiny deposits of the salts and minerals that are normally filtered by the kidneys.
Due to their increased risk for kidney stones, it is recommended that patients with Wilson's disease have an annual x-ray to check for any stones. If small stones are found, these can often be passed with the help of pain relievers, alpha-blockers, and plenty of fluids. Larger stones may require other surgical interventions.
It is characterized by the abnormal destruction of red blood cells, and it is a potential complication for patients with Wilson's disease. This condition causes patients to feel fatigued, and they may also have an increased heart rate and an enlarged spleen or liver. Patients may feel weak, and they could become dizzy or confused.
Patients with Wilson's disease may experience a variety of neurological issues. For example, lack of coordination, gait abnormalities, tremors, and slurred speech could occur. Some individuals might experience involuntary muscle movements or twitching, and speech difficulties have been observed.
For some patients, neurological issues could be accompanied by psychological changes such as depression, irritability, mood swings, and changes in personality. Bipolar disorder and episodes of psychosis may develop.
All Wilson's disease patients need to take some type of medication therapy to remove excess dietary copper every day, for life. In some cases, Wilson’s disease patients may benefit from additional forms of therapy to help control emotional or physical symptoms or regain lost movement or speech.
These other forms of therapy maybe
Physical therapy restores function for individuals who have neuromuscular or skeletal problems like arthritis, osteoporosis, joint and muscle pain, and coordination issues. The physical therapy will include
Exercise and programs to increase muscle function, coordination, balance, and endurance
Training in mobility, gait stability, posture, and positioning
Occupational therapy assists individuals with adapting to their social and physical environment.
Therapists help improve function through:
Activities that help in maintaining memory, orientation, and cognitive integration
Adaptive techniques or equipment to overcome physical disabilities
Education and training in areas such as dressing, bathing, eating, and grooming
People with Wilson’s disease may experience a range of psychological disorders over their lifetimes. Depression is the most common and may happen at a rate that’s more than double that of the general population. The feelings that the person experience are:
Persistent sad, anxious, or empty mood
Feelings of guilt, worthlessness, or helplessness
Thoughts of death or suicide, or suicide attempts
Difficulty sleeping, early-morning awakening, or oversleeping
Difficulty in concentrating, remembering, or making decisions
If any of these are suspected, get in touch with your personal physician or mental health professional for an evaluation.
