Wilson's disease

Background

  • Autosomal recessive
  • Impairment of biliary cellular copper excretion with accumulation in organs (mostly liver, brain, cornea)
  • Liver becomes cirrhotic with ~5% developing liver failure

Clinical Features

  • Hepatic
    • Kayser-Fleischer rings
    • Asymptomatic (steatosis, chronic hepatitis, compensated cirrhosis)
    • Abdominal pain (acute liver failure/hepatitis)
    • Jaundice, hepatomegaly, splenomegaly, ascites
    • Upper GI bleeding sequela of cirrhosis with varices
  • Neurologic symptoms
    • Dysarthria
    • Gait abnormalities
    • Dystonia
    • Tremor
    • Parkinsonism
  • Psychiatric symptoms
    • Depression, personality changes, impulsiveness, psychosis

Differential Diagnosis

  • Viral hepatitis
  • Toxins
  • Alcohol
  • Ischemia
  • Autoimmune hepatitis
  • Essential tremor
  • Parkinson disease
  • Generalized dystonia
  • Depression
  • Bipolar disorder
  • Schizophrenia
  • Dementia
  • Drug abuse


Evaluation

  • LFTs to assess ALT/AST
  • CBC to assess for anemia (followed by testing for Coombs-negative hemolytic anemia)
  • Ocular slit-lamp to assess for Kayser-Flesicher rings
  • Outpatient ceruloplasmin concentration, serums copper concentration, 24-hour urinary copper excretion


Management

  • Potent chelators: D-penicillamine (first-line), trientine (second-line), oral zinc
  • Low-copper diet
  • Screening for hepatocellular carcinoma (HCC) recommended but unclear association


References

1. Lorincz MT. Neurologic Wilson's disease. Ann N Y Acad Sci 2010; 1184:173. 2. Gollan JL, Gollan TJ. Wilson disease in 1998: genetic, diagnostic and therapeutic aspects. J Hepatol 1998; 28 Suppl 1:28. 3. Soltanzadeh A, Soltanzadeh P, Nafissi S, et al. Wilson's disease: a great masquerader. Eur Neurol 2007; 57:80. 4. Stremmel W, Meyerrose KW, Niederau C, et al. Wilson disease: clinical presentation, treatment, and survival. Ann Intern Med 1991; 115:720.