What is the management of Wilson's disease?

Management of Wilson Disease

Initial treatment for symptomatic patients with Wilson disease should include a chelating agent (penicillamine or trientine), while presymptomatic patients or maintenance therapy can be accomplished with either chelating agents or zinc. 1

Initial Treatment Approach

Symptomatic Patients

• Chelating agents are first-line therapy for symptomatic patients to promote copper excretion 1
  • D-Penicillamine: 20 mg/kg/day in 2-4 divided doses, taken 1 hour before or 2 hours after meals 1, 2
  • Trientine: Alternative for patients who cannot tolerate D-penicillamine, administered 1 hour before or 2 hours after meals 1
• Worsening of neurologic symptoms occurs in 10-50% of patients during initial treatment with chelating agents, particularly D-penicillamine 1, 3
• For patients with decompensated liver disease but no encephalopathy, a combination of chelator plus zinc may be used (temporally dispersed throughout the day) 1

Presymptomatic Patients

• Either D-penicillamine, trientine, or zinc is effective in preventing disease progression 1
• Zinc appears preferable for presymptomatic children under age 3 years 1
• Zinc works by inducing enterocyte metallothionein, which binds copper and prevents its absorption 1, 4

Maintenance Therapy

• After adequate treatment with a chelator (typically 1-5 years), stable patients may transition to zinc maintenance therapy 1
• Patients suitable for transition to zinc maintenance should be:
  • Clinically well with normal liver function tests
  • Normal non-ceruloplasmin bound copper concentration
  • 24-hour urinary copper in range of 200-500 μg/day on treatment 1
• Zinc is more selective for removing copper than chelating agents and has fewer side effects 1
• Zinc dosage: 150 mg/day elemental zinc in three divided doses for adults and larger children; 75 mg/day for children <50 kg 1

Monitoring Treatment

• Adequacy of chelation therapy is monitored by:
  • 24-hour urinary copper excretion (target: 200-500 μg/day on treatment) 1
  • Non-ceruloplasmin bound copper concentration (should normalize) 1
• Adequacy of zinc therapy is monitored by:
  • 24-hour urinary copper excretion (should be <75 μg/day on stable treatment) 1
  • Clinical and biochemical improvement 1
  • Urinary zinc excretion (to check compliance) 1

Special Situations

Fulminant Hepatic Failure

• Liver transplantation is life-saving and the only effective option 1
• While awaiting transplantation, plasmapheresis, exchange transfusion, or albumin dialysis may protect kidneys from copper-mediated damage 1

Pregnancy

• Treatment must be maintained throughout pregnancy 1
• Chelating agent dosage should be reduced by 25-50% during the last trimester 1
• Zinc dosage remains unchanged throughout pregnancy 1

Adjunctive Measures

Diet

• Foods with high copper content should be avoided, especially in the first year of treatment:
  • Shellfish, nuts, chocolate, mushrooms, organ meats 1
• Dietary management alone is not recommended as sole therapy 1
• Check copper content of drinking water if using well water or copper pipes 1

Antioxidants

• Vitamin E supplementation may be beneficial as an adjunctive treatment 1
• Serum and hepatic vitamin E levels are often low in Wilson disease 1

Important Considerations

• Treatment should never be terminated indefinitely, even if the patient appears well 1
• Discontinuation of treatment risks development of intractable hepatic decompensation 1
• Experimental agent tetrathiomolybdate shows promise for patients with neurologic symptoms as it appears less likely to cause neurological deterioration 1, 3
• The goal of therapy is to normalize free copper in serum, not necessarily to remove all copper from the liver 5