Wilson's Disease Diagnosis and Treatment
The diagnosis of Wilson's disease requires a high level of clinical suspicion and relies on a combination of laboratory tests including serum ceruloplasmin, 24-hour urinary copper excretion, and liver biopsy with hepatic copper quantification, while treatment should be initiated with chelating agents (D-penicillamine or trientine) for symptomatic liver disease and zinc for neurological presentations or maintenance therapy. 1, 2
Diagnostic Criteria
Key Laboratory Tests
- Serum ceruloplasmin is typically decreased (<20 mg/dL), with sensitivity of 98.2% and specificity of 92.3% 3
- 24-hour urinary copper excretion is elevated (>40 μg/day or 0.6 μmol/day), with sensitivity of 100% but lower specificity of 63% 3
- Serum copper may be elevated in acute liver failure due to Wilson's disease, typically 200 μg/dL or 31.5 μmol/L 1
- Hepatic copper concentration >250 μg/g dry weight on liver biopsy is confirmatory 1
Clinical Features to Consider
- Kayser-Fleischer rings (copper deposits in the cornea) support the diagnosis but may be absent in up to 50% of patients with acute liver failure due to Wilson's disease 1
- Low serum alkaline phosphatase and ratio of alkaline phosphatase to total bilirubin <2 is characteristic in acute liver failure due to Wilson's disease 1
- AST may be higher than ALT, potentially reflecting mitochondrial damage 1
- Modest elevations in serum aminotransferases (typically <2000 IU/L) compared to other causes of acute liver failure 1
Special Clinical Scenarios
- Wilson's disease should be considered in:
- Pediatric patients with autoimmune hepatitis-like presentation 1
- Adults with atypical autoimmune hepatitis or poor response to corticosteroid therapy 1
- Patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis 1, 4
- Patients with acute liver failure with Coombs-negative intravascular hemolysis 1
Family Screening
- First-degree relatives of patients with Wilson's disease must be screened 1
- Screening should include:
Treatment Options
Initial Treatment Based on Presentation
Symptomatic Liver Disease
- D-penicillamine or trientine is recommended as first-line therapy for patients with hepatic symptoms 2, 6
- Zinc monotherapy is not recommended for symptomatic liver disease due to risk of hepatic deterioration 2
- Dosing for D-penicillamine: typically starts at lower doses and increases gradually to avoid hypersensitivity reactions 6
Neurological Presentation
- Zinc may be used as first-line therapy for patients with neurological symptoms 2
- Neurological deterioration is uncommon with zinc therapy compared to chelating agents 2
- Zinc dosage: 150 mg elemental zinc daily in three divided doses for adults and larger children; 75 mg/day in three divided doses for smaller children (<50 kg) 2
Acute Liver Failure
- Liver transplantation is the only effective treatment option for acute liver failure due to Wilson's disease 1, 2
- These patients receive highest priority for transplantation by the United Network for Organ Sharing 1
Asymptomatic/Presymptomatic Patients
- Treatment should be initiated for all individuals greater than 3 years old identified through family screening 1
- Either zinc or a chelating agent is effective in preventing disease progression 2
- Zinc appears preferable for presymptomatic children under the age of 3 years 2
Monitoring Treatment
- Patients should be monitored at least twice yearly, more frequently during initial treatment phase 1, 2
- Laboratory testing should include:
- Target values:
- For patients on chelators: 24-hour urinary copper excretion of 200-500 μg/day (3-8 μmol/day) 1, 2
- For patients on zinc: urinary copper excretion no more than 75 μg/day (1.2 μmol/day) 1, 2
- Recent evidence suggests that clinically stable patients often have values outside these ranges without signs of overtreatment 7
Common Pitfalls and Caveats
- No single test can reliably diagnose or exclude Wilson's disease; a combination of tests is required 8
- Serum ceruloplasmin may be decreased in other conditions such as protein-losing enteropathy, malnutrition, and severe hepatic insufficiency 1, 8
- Interruption of treatment, even for a few days, can lead to sensitivity reactions upon resumption of therapy 6
- Combination treatment with chelator plus zinc requires careful timing (5-6 hours between doses) to avoid having the chelator bind to zinc 2
- Overtreatment can lead to copper deficiency, resulting in neutropenia, anemia, and hyperferritinemia 1, 2
- Treatment must be maintained throughout pregnancy; interruption during pregnancy has resulted in acute liver failure 2
- Regular monitoring for side effects of medications is essential: