What is the treatment for Wilson disease?

Treatment of Wilson Disease

Initial treatment for symptomatic Wilson disease patients should include a chelating agent (penicillamine or trientine), with trientine being preferred due to its better safety profile. 1

Treatment Algorithm Based on Clinical Presentation

Symptomatic Patients

1. Initial Treatment:

   • First-line: Trientine 750-1500 mg/day in 2-3 divided doses for adults 1
   • Alternative: D-penicillamine (if trientine unavailable) 2, 3
   • Take medication 1 hour before or 2 hours after meals for optimal absorption 2

2. Monitoring During Initial Treatment:

   • 24-hour urinary copper excretion (target: 200-500 μg/day on treatment) 2
   • Non-ceruloplasmin bound copper (should normalize with effective treatment) 2
   • Liver function tests and neurological status 2
   • Complete blood count to monitor for bone marrow depression 2

3. Special Clinical Scenarios:

   • Neurological symptoms: Risk of worsening with chelation therapy (10-50% with D-penicillamine) 1
   • Decompensated cirrhosis: Combined therapy with chelator and zinc (temporally dispersed) 2
   • Acute liver failure: Liver transplantation is life-saving 2

Maintenance Therapy

After 1-5 years of successful chelation therapy (clinical improvement, normal liver function, normalized non-ceruloplasmin bound copper):

• Option 1: Continue lower-dose chelation therapy 2
• Option 2: Transition to zinc therapy (150 mg/day in three divided doses) 2, 1
• Zinc is more selective for removing copper than chelators and has fewer side effects 2

Asymptomatic/Presymptomatic Patients

• Adults: Either chelation therapy or zinc is effective 2
• Children under 3 years: Zinc appears preferable due to better safety profile 2, 1

Dietary Management (Adjunctive)

• Avoid foods with high copper content: shellfish, nuts, chocolate, mushrooms, organ meats 2
• Check copper content of water if using copper pipes; flush stagnant water before use 2
• Avoid copper containers or cookware 2
• Dietary management alone is not sufficient therapy 2

Monitoring Treatment Efficacy

• For chelation therapy: 24-hour urinary copper excretion (200-500 μg/day) 2, 1
• For zinc therapy: 24-hour urinary copper excretion (<75 μg/day) 2
• For both: Non-ceruloplasmin bound copper should normalize 2
• Compliance monitoring: Urinary zinc excretion (~2 mg/24 hours) for patients on zinc 2

Important Precautions and Pitfalls

• Never discontinue treatment: Discontinuation can lead to intractable hepatic decompensation 2

• Pregnancy considerations:

  • Wilson's disease: Limit penicillamine to 750 mg/day; reduce to 250 mg/day for last 6 weeks if cesarean planned 3
  • Zinc may be safer during pregnancy 4

• Medication interactions:

  • Avoid iron supplements with trientine (forms toxic complex) 1
  • Separate zinc and chelator administration by 5-6 hours to prevent binding 2

• Side effect monitoring:

  • D-penicillamine: High rate of adverse effects (~30%), including proteinuria, rash, bone marrow depression 3
  • Trientine: Generally better tolerated than penicillamine 1
  • Zinc: Primarily gastric irritation, generally well-tolerated 5

• Experimental therapy: Tetrathiomolybdate shows promise for neurological Wilson disease but remains experimental in the US 2

Wilson disease treatment is lifelong, and regular monitoring is essential to prevent disease progression and manage potential medication side effects. Early diagnosis and appropriate treatment can lead to normal life expectancy and significant improvement in both hepatic injury and neurologic manifestations 6.