Nutrition
|
August 30, 2024

Wilson Disease Care: Key Supplements and Effective Treatment Approaches

Medically Reviewed by
Updated On
September 19, 2024

Wilson disease, also called Wilson’s Disease (WD), first described in 1912 by Kinnear Wilson, is an autosomal recessive genetic disorder of copper metabolism caused by a mutation in the ATP7B gene. This mutation alters the function of the protein transporter responsible for excreting excess copper into bile and out of the body, leading to its accumulation in various organs. 

Basically, it’s when there is a gene mutation that prevents the body from getting rid of extra copper properly. In this article, we will present a comprehensive overview of WD, focusing on the management of the disease and the role of supplements. 

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Why is Too Much Copper Dangerous?

While copper is essential for many physiological processes, its excess can result in systemic manifestations, including liver disease and central nervous system dysfunction. 

WD affects ~1 in 30,000 people worldwide, with around 8,300-11,000 cases in the United States of America, and is classified as a rare disease. It typically presents between the ages of four to 40 years. Diagnosis is based on clinical presentation, various biomarker tests, and genetic tests.

Understanding Wilson’s Disease and Its Management

Wilson’s Disease (WD) is a genetic disorder caused by mutations in the ATP7B gene on chromosome 13. For the disease to appear, a person must inherit two mutated genes, one from each parent.

Screening close relatives of people with WD can help identify those who may be asymptomatic. Individuals with only one mutated gene will not develop the disease but can pass the gene to their children. About one in 90 people are carriers.

Inheritance of Wilson’s Disease. Image from Mayo Clinic. 

Wilson’s Disease (WD) affects how the body manages copper. Normally, a protein called ATP7B helps attach copper to ceruloplasmin in the liver, which then moves copper into the bloodstream and gets rid of the extra through bile. In people with WD, ATP7B doesn’t work properly, leading to copper buildup in the liver. This causes low levels of copper-bound ceruloplasmin in the blood and prevents the body from excreting excess copper.

Over time, copper collects in different organs, which may lead to liver damage, movement issues, mood changes, and a ring of copper in the eyes (Kayser-Fleischer rings).

Symptoms of Wilson’s Disease

Here are the common symptoms often seen in patients with WD. 

Hepatic Symptoms

  • Asymptomatic enlarged liver (hepatomegaly)
  • Elevated liver enzymes (AST, ALT)
  • Fatty liver disease
  • Acute hepatitis
  • Cirrhosis (compensated or decompensated)
  • Acute liver failure
  • Isolated enlarged spleen (splenomegaly)

Neurological Symptoms

  • Slurred speech (dysarthria)
  • Tremors and involuntary movements
  • Difficulty swallowing (dysphagia)
  • Drooling
  • Muscle stiffness (rigid dystonia)
  • Nerve function issues (dysautonomia)
  • Seizures
  • Sleep disorders
  • Pseudobulbar palsy
  • Migraine headaches

Psychiatric Symptoms

  • Depression
  • Bipolar disorder
  • Anxiety
  • Personality changes
  • Psychosis
  • Neurotic behavior

Other Systemic Symptoms

Ocular

Renal

  • Kidney stones (nephrolithiasis)
  • Aminoaciduria

Musculoskeletal

Cardiac

  • Irregular heart rhythms (dysrhythmias)
  • Cardiomyopathy
  • Enlarged heart (left ventricular hypertrophy)

Reproductive

  • Recurrent miscarriages
  • Infertility
  • Irregular menstrual cycles

Endocrine

  • Hypoparathyroidism

Pancreatic

  • Pancreatitis

Dermatologic

How Practitioners Diagnose Wilson’s Disease

Early diagnosis of WD is important to prevent severe liver damage. Diagnosis is based on symptom presentation and various clinical tests. Key diagnostic tests include: 

  • Genetic testing and family screening for the ATP7B gene mutations 
  • Serum ceruloplasmin level
  • 24-hour urine copper test 
  • Slit lamp ophthalmology exam for Kayser-Fleischer rings 
  • Liver biopsy 

How to Treat and Manage Wilson’s Disease (WD)

Treatment for WD falls into three different steps depending on the presentation and symptoms. The treatment approach varies for symptomatic and asymptomatic patients with active disease based on biomarker testing. 

Step 1: Using Copper Chelating Agents

Copper chelating agents are the primary treatment for WD. While D-Penicillamine is the first-line option, about 30% of patients discontinue it due to side effects. To improve tolerability, a "start low and go slow" approach is recommended.

For patients who cannot tolerate D-Penicillamine, trientine hydrochloride is an effective alternative, particularly for those with conditions like thrombocytopenia or neutropenia. Trientine generally has fewer neurological side effects than D-Penicillamine, though direct comparisons are limited.

In 2022, the FDA approved trientine tetrahydrochloride for maintenance therapy in adult patients who tolerate D-Penicillamine. This new option offers twice-daily dosing and does not require refrigeration, potentially improving adherence.

Both D-Penicillamine and trientine hydrochloride are approved for pediatric use, but trientine tetrahydrochloride is not yet approved for children.

Step 2: Using Zinc Supplements for Maintenance

Zinc is a key supplement in WD, helping to reduce copper absorption in the gut and manage copper levels. It is often used for long-term maintenance, especially in asymptomatic patients and those with neurological symptoms. Zinc can also potentially reduce oxidative liver injury from excess copper.

Dosing Recommendations:

  • Adults and children over 50 kg: 150 mg/day in 3 divided doses
  • Children under 50 kg (5 years and older): 75 mg/day in 3 divided doses
  • Children under 50 kg (under 5 years): 50 mg/day in 3 divided doses

Zinc should be taken on an empty stomach, as food can interfere with its absorption. The most common side effect is mild stomach irritation, but in rare cases, early neurological symptoms may worsen.

Forms of Zinc: 

Zinc is available in different forms, such as zinc acetate, sulfate, gluconate, and picolinate. Numerous clinical studies, case reviews, and meta-analyses have shown the effectiveness of zinc salts. Although various forms have been shown to help manage copper levels, only zinc acetate is FDA-approved for maintenance in WD. 

A pooled analysis of 16 studies suggests that zinc can be as effective as D-penicillamine for liver-related WD and may be more effective for neurological symptoms, with fewer side effects. 

Another systematic review of 23 studies indicated similar efficacy with fewer side effects with zinc compared to D-penicillamine. However, further research is needed to compare zinc to copper chelating agents directly in terms of safety and efficacy.

Step 3: Long Term Management

Continued use of supplements helps prevent copper buildup and related symptoms. Regular monitoring of copper levels, free copper (not bound to ceruloplasmin), liver function, and other markers is important. For asymptomatic patients, lower-dose zinc therapy is often used to prevent future issues.

Additional Considerations:

  • Duration: It may take 6 to 18 months of consistent treatment to see symptom improvement and stabilize copper levels.
  • Liver Transplant: This may be considered for patients who do not respond well to chelating agents and zinc, or in cases of severe liver failure.
  • Symptom-Specific Care: Treatment of neurological, psychiatric, and other symptoms should involve a multidisciplinary team for comprehensive care.
  • Vaccinations: Hepatitis A and B vaccines are recommended to help protect the liver from further damage.

Additional Supplements for Managing Wilson’s Disease (WD)

In addition to zinc supplements, the following supplements can be an important part of managing Wilson’s Disease (WD):

Antioxidant Supplements

Vitamin E, a key antioxidant, is considered a helpful supplement for WD due to low levels found in patients. A study showed that WD patients with neurological symptoms saw more improvement when taking 400 mg of vitamin E and 500 mg of vitamin C daily, compared to those without antioxidants. Benefits were observed after six months, suggesting these supplements may support better outcomes.

A study published in 2012 showed a lower antioxidant capacity associated with neurological symptoms in WD. A more recent study reported significantly decreased serum glutathione level in patients with neurological WD. These cases highlight the potential benefits of antioxidants in WD.

Additional supplements like N-acetylcysteine and curcumin may offer further antioxidant support, but should be used with medical supervision.

Selenium Supplements

Low selenium levels are sometimes observed in WD patients with neuropsychiatric symptoms. Copper accumulation in the liver leads to low copper levels in the blood, which is linked with low levels of selenoprotein P. Since selenoprotein P plays a key role in selenium metabolism and has antioxidant properties, selenium supplementation may potentially benefit patients, though further research is needed.

Multivitamins and Minerals

Multivitamins without copper can help address potential deficiencies due to dietary restrictions or treatment. Pregnant women with WD, or those trying to conceive, should consult with a doctor before taking any multivitamins or prenatal vitamins, as some may contain copper.

Other Specific Nutrient Supplements

  • Vitamin B6 supplements at 25-50mg daily may be needed for patients taking D-penicillamine, since this medication may interfere with how the body utilizes vitamin B6.
  • Iron supplements can help prevent anemia in patients on trientine tetrahydrochloride.
  • Certain neurological symptoms of WD, such as tremors and rigidity, are worsened by hypocalcemia (low calcium). Adding a calcium supplement to a patient's daily regimen may help alleviate these symptoms. 
  • Vitamin D deficiency may be associated with bone disease in WD patients. Supplementation may be recommended 

The information provided here is for educational purposes only and is not intended to replace professional medical advice. Always consult with a healthcare provider before starting any new supplements, especially if you have Wilson’s Disease or any other medical condition. Supplements should be used under the supervision of your healthcare team to ensure safety and effectiveness.

Importance of a Balanced Diet and Other Household Considerations  

A balanced diet is important for managing Wilson’s Disease (WD) to ensure proper nutrition and support overall health. Patients should work with a registered dietitian to create a personalized nutrition plan, especially if they are vegetarian, vegan, or have food allergies or digestive issues.

Individuals with Wilson’s Disease should aim to avoid foods high in copper, such as nuts, chocolate, shellfish, soy products, mushrooms, and organ meats, especially during the first year of treatment

For those using well water or water from copper pipes, it’s important to test the water for copper. Levels above 100 μg/L are high for WD and may require treatment. Running the tap for 30 seconds before use and using a water filter can help reduce copper.

Patients should also avoid copper or bronze cookware, especially when cooking acidic foods like tomatoes, as copper can leach into food. Unlined copper utensils should also be avoided.

Practical Considerations for Doctors and Patients

The treatment plan for Wilson’s Disease (WD) should be tailored to each patient, focusing on their specific symptoms. A multidisciplinary team, including specialists and pharmacists, is important for managing the disease and ensuring medication safety. Regular check-ins with this team can improve long-term outcomes and quality of life.

Treatment for WD is lifelong. When started early in patients with liver symptoms, it may help prevent neurological issues. Studies suggest that proper treatment can allow patients to live a normal lifespan. Effective treatment means it works well, is tolerated, and the patient follows it consistently, which is critical for managing WD. However, non-adherence is common, especially in patients without symptoms, as they may not see immediate benefits.

Several factors contribute to non-adherence, including the burden of lifelong therapy, side effects, and frequent follow-ups. A small prospective study from France suggests that a comprehensive care approach can help improve adherence. The WD association offers guidelines on overcoming barriers to treatment, emphasizing the need for supportive, non-judgmental patient education.

Finally, supplements can support WD treatment, but their quality and purity are crucial. Patients should choose medical-grade supplements from reputable manufacturers. Healthcare providers, including pharmacists, can help patients check the copper content of supplements to avoid worsening WD symptoms.

Future Directions in Research and Treatment 

While current treatments for Wilson’s Disease (WD) are effective, they cannot fully correct copper imbalance or cure the condition. Life-long treatment, multiple daily doses, and side effects often lead to poor adherence.

New treatments are being studied in humans with promising results, while others, like cell therapy with liver or stem cell transplants, are being explored in animal models and require more research in humans.

Potential New Treatments and Supplements for Wilson’s Disease 

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Key Takeaways

  • Wilson’s Disease (WD) is a rare genetic disorder caused by mutations in the ATP7B gene, affecting how the body manages copper.
  • Symptoms often include liver, neurological, or psychiatric issues, but some patients may show no symptoms and are diagnosed through genetic screening.
  • First-line treatment involves copper-chelating agents, which are effective in reducing copper buildup. Life-long management is necessary to maintain safe copper levels.
  • Zinc supplements are essential for long-term management of WD, while liver transplantation is an option for patients with severe liver failure or those who do not respond to treatment.
  • Antioxidants and other supplements may help manage symptoms, but should be used under medical supervision.
  • A multidisciplinary care team and patient education are key to improving treatment adherence, quality of life, and long-term outcomes in WD management.
The information in this article is designed for educational purposes only and is not intended to be a substitute for informed medical advice or care. This information should not be used to diagnose or treat any health problems or illnesses without consulting a doctor. Consult with a health care practitioner before relying on any information in this article or on this website.

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The American Journal of Clinical Nutrition
Peer Reviewed Journal
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The Journal of Bone and Joint Surgery
Peer Reviewed Journal
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Kidney International
Peer Reviewed Journal
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The Journal of Allergy and Clinical Immunology
Peer Reviewed Journal
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Annals of Surgery
Peer Reviewed Journal
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Chest
Peer Reviewed Journal
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The Journal of Neurology, Neurosurgery & Psychiatry
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Blood
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Gastroenterology
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The American Journal of Respiratory and Critical Care Medicine
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The American Journal of Psychiatry
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Diabetes Care
Peer Reviewed Journal
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The Journal of the American College of Cardiology (JACC)
Peer Reviewed Journal
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The Journal of Clinical Oncology (JCO)
Peer Reviewed Journal
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Journal of Clinical Investigation (JCI)
Peer Reviewed Journal
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Circulation
Peer Reviewed Journal
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JAMA Internal Medicine
Peer Reviewed Journal
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PLOS Medicine
Peer Reviewed Journal
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Annals of Internal Medicine
Peer Reviewed Journal
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Nature Medicine
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The BMJ (British Medical Journal)
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The Lancet
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Journal of the American Medical Association (JAMA)
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Pubmed
Comprehensive biomedical database
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Harvard
Educational/Medical Institution
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Cleveland Clinic
Educational/Medical Institution
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Mayo Clinic
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The New England Journal of Medicine (NEJM)
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Johns Hopkins
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