Wilson’s Disease

General Information:

  • Typically, we ingest more copper in the diet than necessary – most is excreted through the biliary system (some through the urine)
  • Normally, ingested copper is stored in plasma as ceruloplasmin.
  • Patients with Wilson’s disease, have a decreased rate of copper incorporation into ceruloplasmin and a decreased rate of biliary excretion

Clinical Manifestations:

  • Typically considered a disease that presents in young people, but can present at any age
  • The most common presentations are with liver disease or neuropsychiatric disturbances
  • Wilson’s disease can manifest with an impressive spectrum of neurological, behavioral or psychiatric disorders, which may be its first clinical manifestation, appearing simultaneously with hepatic signs, or some years later.
  • System-specific
    • Liver: cirrhosis; increased bilirubin out of proportion to alkaline phosphatase, which may be abnormally low; AST>>ALT
    • Heme: hemolytic anemia, caused by release of copper into the circulation
    • Neurologic: movement disorder (tremor, poor coordination) or rigid dystonia, including bulbar sx
    • Psych: highly variable—from OCD to psychosis to depression
    • Ocular: Kayser-Fleischer rings caused by copper deposition (not required for dx, nor are they specific for Wilson’s—may be found in other types of chronic liver disease)
    • Renal: Fanconi’s syndrome (proximal tubular dysfunction resulting in Type 2 RTA, glucosuria with normal serum glucose, hypouricemia and hypophosphatemia)
    • Also: arthritis, cardiomyopathy, rhabdo, pancreatitis

Diagnostic Tests: 

  • Serum ceruloplasmin: classically, this is low. May be normal in up to 5% of patients; can also be low in other forms of chronic liver disease
  • 24 hour urinary copper: elevated; good confirmatory test
  • Slit-lamp exam for Kayser-Fleischer ring
  • Liver biopsy

Management:

  • Copper chelation: penicillamine, trientene, or zinc
  • Fulminant hepatic failure generally requires transplant
  • Family screening is key for siblings of those affected, as early treatment can greatly improve prognosis