What is the treatment for Wilson disease in children?

Treatment of Wilson Disease in Children

The treatment of Wilson disease in children requires lifelong medication with chelating agents or zinc, with the specific regimen depending on disease presentation and severity. 1

Initial Treatment Approach

For Presymptomatic Children

• Zinc therapy is preferable for presymptomatic children under 3 years of age 1
  • Dosage: 25 mg elemental zinc twice daily 1
  • Advantages: More selective for copper removal with fewer side effects

For Symptomatic Children

• Chelating agents are the first-line treatment:

  1. D-penicillamine:

     • Dosage: 20 mg/kg/day divided into 2-3 doses 1
     • Administer 1 hour before meals (food inhibits absorption)
     • Add pyridoxine supplementation (25-50 mg/day) to prevent deficiency 1

  2. Trientine:

     • Dosage: 10 mg/kg/day divided into 2-4 doses 1
     • Better tolerated than D-penicillamine with fewer adverse effects 2

For Decompensated Liver Disease

• Combination therapy with both chelator and zinc:
  • Zinc (25 mg elemental in children) as first and third doses
  • Trientine (10 mg/kg) as second and fourth doses
  • Must separate doses by 5-6 hours to prevent binding between agents 1
  • After 3-6 months, transition to monotherapy if patient responds 1

For Acute Liver Failure

• Liver transplantation is life-saving and the only effective option 1
• While awaiting transplantation:
  • Plasmapheresis, hemofiltration, or exchange transfusion to protect kidneys 1
  • Albumin dialysis may temporarily stabilize the patient 1

Monitoring Treatment

• Monitor patients at least twice yearly, more frequently during initial treatment 1
• Assessment should include:
  • Physical examination for liver disease and neurological symptoms
  • 24-hour urinary copper excretion (target: 200-500 μg/day during maintenance) 1
  • Liver function tests
  • Complete blood count (to monitor for side effects)

Treatment Considerations and Pitfalls

Medication-Specific Considerations

1. D-penicillamine:

   • Most effective but highest rate of adverse effects in children 2
   • Common side effects: hypersensitivity reactions, bone marrow suppression, proteinuria
   • Approximately 5% treatment ineffectiveness rate in children 2

2. Trientine:

   • Better tolerated than D-penicillamine with fewer adverse effects
   • Higher treatment ineffectiveness rate (44%) compared to D-penicillamine 2

3. Zinc:

   • Good option for maintenance therapy and presymptomatic children
   • Moderate effectiveness (25% ineffectiveness rate) 2
   • Works by inducing metallothionein and blocking intestinal copper absorption 3

Important Cautions

• Treatment must never be discontinued - interruption can lead to intractable hepatic decompensation 1
• Dietary restrictions: avoid foods high in copper (shellfish, nuts, chocolate, mushrooms, organ meats) especially during first year of treatment 1
• Avoid using copper containers or cookware 1
• Check copper content of water if using well water or copper pipes 1

Special Situations

Very Young Children

• WD can present as early as 2 years of age 4
• Diagnosis may be challenging as biochemical tests are less sensitive in very young children 4
• Liver copper quantification (>250 μg/g dry weight) may be required for diagnosis 4

Family Screening

• Essential to screen siblings of affected children (25% chance of being homozygous) 1
• Genetic testing is the most reliable method to identify affected siblings 1
• Begin treatment for all affected children over 3 years old, even if asymptomatic 1

The goal of therapy is to normalize free copper in serum, which leads to significant improvement in hepatic injury and neurologic manifestations, allowing for normal life expectancy with consistent treatment 3.