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

Critical Diagnostic Patterns

Acute liver failure from Wilson disease has a distinctive constellation: Coombs-negative hemolytic anemia, modest aminotransferase elevations, markedly low or normal alkaline phosphatase, coagulopathy unresponsive to vitamin K, and rapid progression to renal failure 1

Autoimmune hepatitis mimicry is common—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 1

Treatment Strategy

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

Symptomatic Patients

Initial treatment with chelating agents is standard for symptomatic patients 1:

• Trientine is preferred when D-penicillamine causes adverse reactions 1
• Penicillamine is FDA-approved for Wilson disease treatment, though neurologic symptoms may worsen during initiation—the drug should not be withdrawn despite this 2
• Noticeable improvement may not occur for 1-3 months 2
• If neurological symptoms worsen for a month after initiating penicillamine, consider 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: 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 patients 1:

• Zinc is preferable for children under age 3 years 1
• Either zinc or chelators are 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 provide satisfactory control in many cases 3

Maintenance Therapy

After 1-5 years of chelation with clinical stability, transition to zinc monotherapy or continue reduced-dose chelator 1:

• Stable patients demonstrate normal aminotransferases and hepatic synthetic function 1
• Clinical parameters including neuropsychiatric status, speech, and liver function tests should remain stable or improve 3

Pregnancy Management

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

• Zinc dosage continues unchanged 1
• Chelator dosage reduced by 25-50% 1
• 19 women in clinical trials delivered 26 live births while continuing zinc acetate therapy with adequate copper control 3

Dietary Modifications

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

• Exclude chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and copper-enriched cereals 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:

• History and physical examination 1
• Serum ceruloplasmin and copper 1
• Liver function tests 1
• Slit-lamp examination 1
• ATP7B haplotype analysis or mutation testing 1