What is the recommended initial treatment for Wilson disease in children based on European Association for the Study of the Liver (EASL) or American Association for the Study of Liver Diseases (AASLD) guidelines?

Initial Treatment for Wilson Disease in Children

For children with symptomatic hepatic Wilson disease, initiate treatment with a chelating agent (D-penicillamine or trientine), NOT zinc monotherapy, as zinc alone has led to hepatic deterioration and fatal outcomes in this population. 1

Treatment Selection Based on Clinical Presentation

Symptomatic Hepatic Disease (Most Common in Children)

• Start with chelating agents as first-line therapy 2, 1
• D-penicillamine: 20 mg/kg/day rounded to nearest 250 mg, divided into 2-3 doses, taken 1 hour before meals 2
• Trientine (alternative): 10 mg/kg/day in divided doses 1
• Add pyridoxine supplementation 25-50 mg/day when using D-penicillamine, as it interferes with pyridoxine action 2
• Zinc monotherapy is contraindicated in symptomatic hepatic disease due to documented fatal outcomes 1

Symptomatic Neurological Disease

• Zinc may be considered as first-line therapy to avoid neurological worsening 1
• D-penicillamine carries a 10-50% risk of worsening neurological symptoms during initial treatment 1
• If chelator is chosen and neurological symptoms worsen, switch to zinc immediately 1

Presymptomatic Children (Identified Through Family Screening)

• Either chelating agent OR zinc monotherapy is acceptable 2, 1
• Zinc monotherapy has proven highly effective and safe in presymptomatic pediatric patients, including very young children 3, 4
• For children under 6 years: 50 mg elemental zinc daily in divided doses 4
• For children 6-10 years or <50 kg: 75 mg elemental zinc daily in 3 divided doses 1
• For children >50 kg: 150 mg elemental zinc daily in 3 divided doses 1

Specific Dosing Regimens

D-Penicillamine

• 20 mg/kg/day rounded to nearest 250 mg 2
• Divide into 2-3 doses taken 1 hour before meals 2
• Mandatory pyridoxine 25-50 mg/day to prevent deficiency 2

Trientine

• 10 mg/kg/day in divided doses 1
• Alternative when D-penicillamine is not tolerated 2

Zinc (When Appropriate)

• Children <50 kg: 75 mg elemental zinc daily in 3 divided doses 1
• Children >50 kg: 150 mg elemental zinc daily in 3 divided doses 1
• Take 30 minutes before meals for optimal absorption 1

Monitoring During Initial Treatment

First Year: Every 3 Months 1

• Liver function tests (ALT, AST, bilirubin, albumin, PT/INR) 1
• 24-hour urinary copper excretion 2, 1
  • On chelator therapy: Target 200-500 μg/day (3-8 μmol/day) 2, 1
  • On zinc therapy: Target <75 μg/day (1.2 μmol/day) 2, 1
• Non-ceruloplasmin-bound copper concentration 2

After Stabilization: At Least Twice Yearly 1

• Continue same laboratory parameters 1
• Monitor for treatment adherence and side effects 2

Dietary Modifications

First Year of Treatment (Mandatory)

• Avoid high-copper foods: shellfish, nuts, chocolate, mushrooms, organ meats 2, 1
• Dietary management alone is never sufficient as sole therapy 2, 1
• Check well water or copper pipe water for copper content 2

Adjunctive Treatment

• Consider vitamin E supplementation as levels are often low in Wilson disease 2, 1

Critical Pitfalls to Avoid

Never Discontinue Treatment

• Treatment must be lifelong—even brief interruptions can cause intractable hepatic decompensation 2, 1
• This is the most common cause of treatment failure 2

Zinc Monotherapy Contraindications

• Never use zinc alone in symptomatic hepatic disease 1
• Risk of inadequate copper removal outweighs safety advantages 1
• Fatal outcomes have been documented 1

D-Penicillamine Risks

• 10-50% risk of neurological worsening in patients with neurological symptoms 1
• Monitor closely during first weeks of treatment 1
• Switch to zinc if neurological deterioration occurs 1

Transition to Maintenance Therapy

Timing: After 1-5 Years of Successful Chelator Therapy 2, 1

Criteria for Transition 2, 1

• Clinically well with stable symptoms 2
• Normal liver enzymes and synthetic function 1
• Normal non-ceruloplasmin-bound copper 1
• Urinary copper 200-500 μg/day on chelator therapy 2, 1

Maintenance Options 2, 1

• Transition to zinc monotherapy (preferred for long-term safety) 2
• Continue reduced-dose chelator 1
• Zinc is more selective for copper removal with fewer side effects 2

Acute Liver Failure Presentation

• Liver transplantation is the only life-saving treatment 1
• Do not delay transplant evaluation in fulminant hepatic failure 1