- Clinical science
Wilson disease (hepatolenticular degeneration) is an autosomal recessive metabolic disorder in which impaired copper excretion causes copper to accumulate in the body. In its initial stages, Wilson disease leads to copper deposits in the liver. As the disease progresses, copper also accumulates in other organs, most importantly in the brain and cornea. The disease often goes undiagnosed until the typical combination of hepatitis (or even cirrhosis), dementia, and parkinsonism raises clinical suspicion. Kayser-Fleischer rings, brownish copper deposits visible around the iris, are a further indication of Wilson disease. Low serum ceruloplasmin (copper transport protein) concentrations and increased urinary copper excretion confirm the diagnosis. Genetic testing or liver biopsies with quantitative copper assays can provide further information if the diagnosis is indeterminate. Primary management consists of maintaining a low-copper diet and the administering a chelating agent such as penicillamine. The prognosis is good if the condition is diagnosed and treated early.
- Age of onset: 5–35 years; (mean age 12–23 years)
- Prevalence: ∼ 1/30,000
Epidemiological data refers to the US, unless otherwise specified.
- Autosomal recessive mutations in the ATP7B gene (Wilson gene) on chromosome 13, which encodes for a membrane-bound, copper-transporting ATPase → defective ATP7B protein
- Results in ↑ free serum copper → accumulation in the liver, cornea, CNS (basal ganglia, brain stem, cerebellum), and enterocytes
- Liver: different degrees of liver disease possible, including acute liver failure, acute or chronic hepatitis, and cirrhosis
- Kayser-Fleischer rings: Copper accumulation in Descemet membrane of the cornea results in 1–2 mm wide, green-brown rings in the periphery of the iris.; While the rings are characteristic for Wilson disease and occur in ∼ 98% of patients who also have neurological symptoms, their absence does not rule out the condition.
- Neurological symptoms: extrapyramidal motor disturbances, but no sensory changes
Wilson disease should be suspected in cases of nonspecific, noninfectious liver disease and nonspecific extrapyramidal movement disorders appearing before the age of 35!
- Slit lamp examination: Kayser-Fleischer rings (best initial test)
- Blood tests
- ↑ Urine copper excretion (over 24 hours)
- Liver biopsy: if other tests are inconclusive
- Screen family members for mutation if diagnosis is confirmed.
- Low-copper diet: avoid foods such as organs, shellfish, nuts, and chocolate
- Regular check-ups: liver biochemical tests every 6 months if disease is stable
- Liver transplantation in cases of fulminant liver failure
Initial therapy: chelating agents
- : side effects in ∼ 30% of cases (e.g., sensitivity reactions)
- Alternatives: trientine or zinc salts
- Maintenance therapy: zinc salts; or low dose chelating agents
Treatment with a chelating agent should be administered gradually over the course of 3 to 6 months, as mobilizing the copper stored in tissues too rapidly may exacerbate neurological symptoms!