What is the treatment for Wilson disease?

Treatment of Wilson Disease

Trientine is the first-line treatment for symptomatic Wilson disease patients due to its better safety profile compared to D-penicillamine, at a dose of 750-1500 mg/day in 2-3 divided doses for adults. 1

Initial Treatment Approach

For Symptomatic Patients:

• Chelating agent therapy:
  • Trientine: 750-1500 mg/day in 2-3 divided doses, administered 1 hour before or 2 hours after meals 2, 1
  • D-penicillamine (alternative): 750-1500 mg/day in 2-3 divided doses, with pyridoxine 25-50 mg daily supplementation 2, 3
    • Note: D-penicillamine has higher adverse effects (30% of patients) and neurological worsening occurs in 10-50% of patients during initial treatment 2, 1

For Presymptomatic/Asymptomatic Patients:

• Zinc therapy: 150 mg elemental zinc/day in three divided doses, taken 30 minutes before meals 1
• Alternatively, a chelating agent (trientine or D-penicillamine) can be used 2

For Fulminant Hepatic Failure:

• Liver transplantation is life-saving and the definitive treatment 2, 1
• While awaiting transplant: plasmapheresis, hemofiltration, or albumin dialysis to protect kidneys from copper damage 2, 1

Combination Therapy

For severe cases, consider combination therapy with both chelator and zinc (separated by 5-6 hours to prevent binding):

• Typical regimen: zinc (50 mg elemental) as first and third doses, and trientine (500 mg) as second and fourth doses 1
• This intensive induction regimen may be transitioned to monotherapy after 3-6 months if responding well 1

Maintenance Therapy

After adequate initial treatment (typically 1-5 years):

• Transition to zinc therapy for long-term maintenance 2, 1
• Criteria for transition: clinically well patient with normal liver function tests, normal non-ceruloplasmin bound copper, and 24-hour urinary copper in the range of 200-500 μg/day on treatment 2

Dietary Management

• Avoid foods with high copper content: shellfish, nuts, chocolate, mushrooms, and organ meats 2, 1
• Check copper content of water if using copper pipes; flush stagnant water before use 2, 1
• Avoid copper containers or cookware 1
• Note: Dietary management alone is insufficient and must be used with medical treatment 2, 1

Monitoring Treatment

Laboratory Parameters:

• For chelation therapy: 24-hour urinary copper excretion (target: 200-500 μg/day) 2, 1
• For zinc therapy: 24-hour urinary copper excretion (target: <75 μg/day) 1
• Non-ceruloplasmin bound copper concentration 2, 1
• Liver function tests every 3-6 months 1, 3
• Complete blood count for patients on chelators 1

Clinical Monitoring:

• Neurological symptoms and liver function 1
• Monitor for proteinuria and hematuria (potential signs of membranous glomerulopathy) 3
• Annual x-ray for renal stones in cystinuria patients 3

Special Considerations

Pregnancy:

• Treatment must be maintained throughout pregnancy 2, 1
• For Wilson disease patients, limit D-penicillamine to 750 mg/day during pregnancy 3
• Consider reducing dose of chelators by 25-50% in the last trimester 1
• D-penicillamine should be avoided during breastfeeding 1

Treatment Challenges:

• Neurological symptoms may worsen initially with chelation therapy, especially D-penicillamine 2, 1
• Treatment should never be discontinued indefinitely, as this can lead to hepatic decompensation within 1-12 months 2, 1
• Medication interactions: avoid iron supplements with trientine (forms toxic complex) 1

Emerging Therapies

• Tetrathiomolybdate: Currently experimental in the US, shows promise for initial treatment of patients with neurologic symptoms with less risk of neurological worsening 2, 4, 5
• Gene therapy: Potential future treatment approach 6

Remember that Wilson disease requires lifelong treatment, and interruption of therapy can lead to serious complications including fulminant hepatic failure 2, 1. Early recognition and prompt initiation of appropriate therapy are critical for preventing permanent damage to the liver and brain 7.