What is the treatment for Wilson's disease?

Treatment of Wilson's Disease

Symptomatic patients with Wilson's disease should receive a chelating agent (D-penicillamine or trientine) as first-line therapy, while zinc may be used as first-line therapy in neurological patients or for maintenance treatment. 1

Initial Treatment Based on Presentation

Symptomatic Hepatic Disease

• D-penicillamine or trientine is recommended as first-line therapy for patients with hepatic symptoms 1
• Zinc monotherapy is not recommended for symptomatic liver disease due to reports of hepatic deterioration and even fatal outcomes 1
• For patients with acute liver failure due to Wilson's disease, liver transplantation is the only effective treatment option 1

Neurological Disease

• Zinc may have a role as first-line therapy in patients with neurological symptoms 1
• If using chelating agents in neurological disease, trientine may be preferred over D-penicillamine as it has a lower risk of neurological deterioration 2
• Neurological deterioration is uncommon with zinc therapy 1

Asymptomatic/Presymptomatic Patients

• Treatment with either zinc or a chelating agent is effective in preventing disease symptoms or progression 1
• Zinc appears preferable for presymptomatic children under the age of 3 years 1

Specific Medications and Dosing

D-Penicillamine

• FDA-approved for Wilson's disease 3
• Dosage: 15-25 mg/kg daily in the early stages of treatment 4
• Should be given at least 2 hours before meals 4
• Side effects occur in 20-25% of patients and may include serious reactions like systemic lupus erythematosus and nephrotic syndrome 4
• Temporary interruption carries an increased risk of developing sensitivity reactions upon resumption 3

Trientine

• Alternative chelating agent for patients who cannot tolerate D-penicillamine 4
• Dosage: 40-50 mg/kg daily, administered similarly to D-penicillamine 4
• Better tolerated than D-penicillamine with fewer adverse events 2

Zinc

• FDA-approved for maintenance treatment of Wilson's disease in patients initially treated with a chelating agent 5
• Mechanism: Induces enterocyte metallothionein which binds copper and prevents its absorption 1
• Dosage for adults and larger children: 150 mg elemental zinc daily in three divided doses 1
• Dosage for smaller children (<50 kg): 75 mg/day in three divided doses 1
• Should be taken at least twice daily to be effective 1
• Taking zinc with food interferes with absorption and effectiveness 1
• Side effects are minimal, with gastric irritation being the most common 1

Monitoring Treatment

• Patients should be monitored at least twice yearly, more frequently during initial treatment phase 1
• Laboratory testing should include liver function tests and indices of copper metabolism 1
• For patients on chelators, 24-hour urinary copper excretion should be 200-500 μg/day (3-8 μmol/day) 1
• For patients on zinc, urinary copper excretion should be no more than 75 μg/day (1.2 μmol/day) 1
• Compliance with zinc therapy can be checked by measuring serum zinc or 24-hour urinary zinc excretion 1

Adjunctive Treatments

Dietary Management

• Avoid foods with high copper concentrations (shellfish, nuts, chocolate, mushrooms, organ meats) 1
• Diet should contain no more than 1-2 mg of copper daily 3
• Dietary management alone is not recommended as sole therapy 1
• Use distilled or demineralized water if drinking water contains more than 0.1 mg/L of copper 3

Antioxidants

• Vitamin E may have a role as adjunctive treatment 1
• Serum and hepatic vitamin E levels are often low in Wilson's disease 1
• Some reports of symptomatic improvement with vitamin E supplementation, though no rigorous studies have been conducted 1

Special Situations

Pregnancy

• Treatment must be maintained throughout pregnancy 1
• Interruption of treatment during pregnancy has resulted in acute liver failure 1
• Zinc dosage is maintained without change during pregnancy 1
• Dosages of chelating agents should be reduced by 25-50% during the last trimester 1

Liver Transplantation

• Indicated for acute liver failure and decompensated cirrhosis unresponsive to medical therapy 1
• One-year survival following liver transplantation ranges from 79-87% 1
• Corrects the hepatic metabolic defects of Wilson's disease 1

Treatment Challenges and Pitfalls

• Neurological symptoms may worsen during initial therapy with D-penicillamine; despite this, the drug should not be withdrawn 3
• Combination treatment with chelator plus zinc requires careful timing (5-6 hours between doses) to avoid having the chelator bind to zinc 1
• Non-compliance with treatment can lead to hepatic deterioration 1
• Overtreatment can lead to copper deficiency, resulting in neutropenia, anemia, and hyperferritinemia 1