What is the recommended treatment for managing disorders of copper metabolism, such as Wilson's disease?

Treatment of Wilson's Disease

The first-line treatment for Wilson's disease should be a chelating agent (D-penicillamine or trientine) for symptomatic patients, while zinc therapy is appropriate for presymptomatic patients or as maintenance therapy after initial chelation. 1

Treatment Algorithm Based on Clinical Presentation

1. Symptomatic Patients (Hepatic or Neurological Symptoms)

Initial Treatment Options:

• D-penicillamine:

  • Dosage: Start with 250-500 mg/day and gradually increase to 1000-1500 mg/day in 2-4 divided doses 1
  • Administration: Take on empty stomach, at least 1 hour before meals or 2 hours after meals 2
  • Monitoring: Complete blood count, urinalysis, and 24-hour urinary copper (target: 200-500 μg/day or 3-8 μmol/day) 1

• Trientine (especially for patients with neurological symptoms or those intolerant to D-penicillamine):

  • Dosage: 1000-2000 mg/day in 2-3 divided doses 3
  • Administration: Same as D-penicillamine, on empty stomach
  • Monitoring: Same as D-penicillamine

Cautions:

• Neurological deterioration occurs in 10-50% of patients treated with D-penicillamine and less frequently with trientine 1
• D-penicillamine has more adverse effects (30% requiring discontinuation) including early sensitivity reactions, bone marrow toxicity, and nephrotoxicity 1

2. Presymptomatic Patients (Identified through Family Screening)

• Zinc therapy:
  • Dosage: 150 mg elemental zinc daily in three divided doses for adults and children >50 kg; 75 mg daily for smaller children 1
  • Administration: 30 minutes before meals 1
  • Monitoring: 24-hour urinary copper excretion (target: <75 μg/day or <1.2 μmol/day) 1

3. Maintenance Therapy

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

• Switch to zinc therapy for long-term maintenance 1
• Continue lower dose of chelating agent as an alternative 1

Monitoring Treatment Efficacy

• Clinical improvement of symptoms
• Liver biochemistries (transaminases, bilirubin, alkaline phosphatase)
• 24-hour urinary copper excretion
• Non-ceruloplasmin bound copper levels
• For zinc therapy: urinary zinc excretion to check compliance 1

Dietary Management

• Avoid foods high in copper: shellfish, nuts, chocolate, mushrooms, organ meats 1
• Limit copper content to <1 mg/day in early treatment stages 4
• Check copper content in drinking water, especially if using copper pipes 1
• Flush water systems before using water for consumption 1
• Avoid using copper cookware 1
• Consider dietitian consultation, especially for vegetarians 1

Experimental Therapies

• Ammonium Tetrathiomolybdate (TM): Not commercially available in the US, but shows promise for neurological Wilson's disease with potentially less risk of neurological deterioration 1

Common Pitfalls and Caveats

1. Delayed diagnosis: Wilson's disease is often fatal if untreated, so early diagnosis and treatment are critical 5

2. Medication timing: Taking chelating agents or zinc with food significantly reduces their effectiveness 1

3. Monitoring compliance: Poor compliance leads to disease progression within 1-12 months; regular monitoring of 24-hour urinary copper excretion is essential 1

4. Neurological worsening: Initial neurological deterioration may occur with chelation therapy, particularly with D-penicillamine; consider starting with lower doses and gradually increasing 1

5. Lifelong treatment: Treatment must be continued for life; discontinuation leads to copper reaccumulation and disease progression 1

6. Combination therapy: If using both chelator and zinc, administer at widely spaced intervals during the day to prevent neutralization of zinc's effectiveness 1

Wilson's disease treatment is lifelong, and with proper medication and monitoring, most patients can achieve normal life expectancy and quality of life 6.