What is the recommended treatment for Wilson disease in children?

Treatment of Wilson Disease in Children

For children with Wilson disease, the recommended first-line treatment is a chelating agent (D-penicillamine or trientine), with zinc therapy being preferable for presymptomatic children under 3 years of age. 1

Initial Treatment Approach

Symptomatic Patients

• Chelating agents are the mainstay of initial treatment:

  • D-penicillamine: 20 mg/kg/day in 2-3 divided doses
  • Trientine: 20 mg/kg/day in 2-3 divided doses (rounded to nearest 250 mg)

• Administration timing: Take 1 hour before or 2 hours after meals to maximize absorption 1

• Monitoring effectiveness:

  • 24-hour urinary copper excretion (target: 200-500 μg/day on treatment)
  • Normalization of non-ceruloplasmin bound copper
  • Clinical improvement and normalization of liver function tests

Presymptomatic Children

• For children under 3 years: Zinc therapy is preferable 1
• For children over 3 years: Either chelating agents or zinc therapy can be used 1

Zinc Therapy

• Dosing:

  • Children <50 kg: 75 mg/day elemental zinc in three divided doses
  • Children >50 kg: 150 mg/day elemental zinc in three divided doses 1

• Administration: Must be taken at least 2 hours apart from food to ensure effectiveness

• Monitoring:

  • 24-hour urinary copper excretion (should be <75 μg/day on stable treatment)
  • Urinary zinc excretion (to check compliance)

Special Clinical Scenarios

Decompensated Cirrhosis

• Combination therapy with both chelator and zinc:

  • Zinc (25 mg elemental in children) as first and third doses
  • Trientine (10 mg/kg in children) as second and fourth doses
  • Must be given at least 5-6 hours apart to prevent interaction 1

• Referral: Prompt referral to a transplant center is essential as some patients may fail medical therapy

Acute Liver Failure

• Liver transplantation is life-saving and the only effective option 1
• Bridge to transplant: Plasmapheresis, hemofiltration, or exchange transfusion to protect kidneys from copper-mediated damage

Maintenance Therapy

After 1-5 years of successful initial treatment:

• Option 1: Continue chelating agent at lower dose
• Option 2: Transition to zinc therapy
  • Advantages: More selective for copper removal and fewer side effects 1

Important: Treatment must never be terminated indefinitely, as discontinuation risks intractable hepatic decompensation 1

Adjunctive Measures

Diet Modifications

• Avoid high-copper foods in first year of treatment:
  • Shellfish, nuts, chocolate, mushrooms, organ meats
• Dietary management alone is insufficient as sole therapy 1

Antioxidant Therapy

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

Common Pitfalls and Caveats

1. Neurological deterioration: D-penicillamine must be introduced slowly due to risk of neurological worsening, especially in patients with brain changes 2

2. Medication compliance: Critical for successful treatment - non-adherence can lead to disease progression and death

3. Delayed diagnosis: Early diagnosis and treatment are essential for preventing irreversible organ damage 3

4. Medication interactions: Neuroleptics may cause exacerbation and should be used at low doses for the shortest period possible 2

5. Treatment monitoring: Regular assessment of 24-hour urinary copper excretion and clinical status is necessary to ensure adequate copper control

The management of Wilson disease in children requires lifelong treatment with careful monitoring. With appropriate therapy, children can achieve near-normal longevity with generally good health 3.