What is the diagnosis and treatment for a patient with suspected Wilson disease?

Wilson Disease: Diagnosis and Treatment

Diagnostic Approach

Wilson disease must be suspected in any patient aged 3-45 years presenting with unexplained liver abnormalities, neurologic symptoms, or psychiatric manifestations, though cases can occur from age 5 to the eighth decade. 1

Essential Diagnostic Tests

No single test confirms or excludes Wilson disease—diagnosis requires multiple complementary evaluations 1:

• Slit-lamp examination for Kayser-Fleischer rings (must be performed by experienced observer): Present in 50-62% of hepatic presentations and nearly all neurologic cases 1
• Serum ceruloplasmin: Values <20 mg/dL support diagnosis 2
• 24-hour urinary copper excretion: Elevated levels indicate excess copper 1
• Liver biopsy with hepatic copper quantification: Diagnostic if >250 μg/g dry weight; normal values (<40-50 μg/g) essentially exclude Wilson disease 1
• ATP7B mutation analysis: Detects mutations in 84.4% of alleles when diagnosis remains uncertain 1
• Brain MRI: Shows basal ganglia abnormalities in 77.7% of patients, even before symptom onset 1

Acute Liver Failure Pattern

Wilson disease presenting as acute liver failure has distinctive features 1:

• Coombs-negative hemolytic anemia
• Modest aminotransferase elevations
• Markedly low or normal alkaline phosphatase
• Coagulopathy unresponsive to vitamin K
• Rapid progression to renal failure

Critical Diagnostic Pitfall

All children with apparent autoimmune hepatitis and any adult failing to respond rapidly to corticosteroids must be carefully evaluated for Wilson disease before continuing immunosuppression, as autoimmune hepatitis mimicry is common. 1

Treatment Strategy

Fundamental Principle

Lifelong treatment is mandatory and must never be discontinued, as interruption risks intractable hepatic decompensation or acute liver failure. 1

Acute Liver Failure

Liver transplantation is the only effective life-saving option for acute liver failure and should be pursued immediately, with one-year survival of 79-87% and excellent long-term survival thereafter. 1

Initial Treatment for Symptomatic Patients

Chelating agents are standard initial treatment for symptomatic patients, with trientine preferred when D-penicillamine causes adverse reactions. 1

• D-penicillamine is FDA-approved for Wilson disease and produces marked neurologic improvement, fading of Kayser-Fleischer rings, and gradual amelioration of hepatic dysfunction 2
• Noticeable improvement may not occur for 1-3 months 2
• Warning: Neurologic symptoms occasionally worsen during initiation of penicillamine therapy—despite this, the drug should not be withdrawn, as temporary interruption increases risk of sensitivity reactions upon resumption 2
• If neurological symptoms continue worsening for a month after initiating penicillamine, consider several short courses of 2,3-dimercaprol (BAL) while continuing penicillamine 2

Decompensated Cirrhosis

Combination therapy with chelator plus zinc, temporally separated by 5-6 hours, is recommended for decompensated cirrhosis: zinc 50 mg elemental and trientine 500 mg as doses 1 and 2, respectively. 1

Presymptomatic/Asymptomatic Patients

Treatment prevents disease progression indefinitely in presymptomatic/asymptomatic patients, with zinc preferable for children under age 3 years and either zinc or chelators effective for older individuals. 1

• Zinc acetate at 25 mg three times daily or 50 mg three times daily maintains adequate copper balance 3
• Once-daily dosing does not give satisfactory control in many cases and would be inadequate in patients with poor compliance 3
• Treatment of asymptomatic patients for over 30 years demonstrates that symptoms and signs appear to be prevented indefinitely with continued daily therapy 2

Maintenance Therapy

After 1-5 years of chelation with clinical stability (normal aminotransferases and hepatic synthetic function), transition to zinc monotherapy or continue reduced-dose chelator. 1

Pregnancy Management

Treatment must be maintained throughout pregnancy without interruption, as discontinuation has resulted in acute liver failure. 1

• Zinc dosage continued unchanged 1
• Chelator dosage reduced by 25-50% during pregnancy 1
• In 19 women with 26 live births who continued zinc acetate therapy, no adverse effects on liver or neurological functions were reported, though limited data shows 7.7% birth defect rate versus 4% in general population 3

Dietary Copper Restriction

Daily diet should contain no more than 1-2 mg copper 2:

• Exclude chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and copper-enriched cereals/supplements 2
• Use distilled or demineralized water if drinking water contains >0.1 mg/L copper 2

Family Screening

All first-degree relatives must be screened, as presymptomatic treatment prevents disease progression. 1

Screening includes 1:

• History and physical examination
• Serum ceruloplasmin and copper
• Liver function tests
• Slit-lamp examination
• ATP7B haplotype analysis or mutation testing