Wilson Disease

 

Wilson disease (also called hepatolenticular degeneration, Westphal-Struempell disease, Westphal pseudosclerosis) is an autosomal recessive inherited disorder of copper metabolism.

Epidemiology

  • Incidence – 1/30,000
  • Age – onset of symptoms prior to age 40

Inheritance

  • Autosomal recessive transmission
  • Caused by mutation in the ATP7B gene (located on chromosome 13)

Pathophysiology

  • Ceruloplasmin, a late acute phase reactant, is the principal copper-containing protein of plasma
  • Disease results from the absence or dysfunction of copper-transporting ATPases that reside in the trans-Golgi network of all cells
  • A variant P-type ATPase prevents incorporation of copper into ceruloplasmin, consequently elevating the concentration of circulating free copper
  • Excess copper is deposited in the kidneys, liver (where it causes cirrhosis), eyes (Kaiser-Fleischer rings) and brain (where it damages the basal ganglia)
  • Other conditions that prevent elimination of copper, such as biliary obstruction, may also lead to elevated free copper concentrations

Clinical Presentation

  • Ophthalmic manifestations
    • Kayser-Fleischer rings (copper deposit on Descemet membrane of cornea)
      • Seen in 50-60% of patients
      • Not specific for Wilson – can be seen in chronic cholestasis
      • Presence does not correlate with severity
  • Hepatic manifestations – hepatomegaly, fatty liver, hepatitis, cirrhosis
  • Neurologic manifestations – movement disorders
    • Movement disorders that typically develop in the third decade and affect 40-50% of patients
    • Dystonia, tremor, incoordination
    • Bulbar and pseudobulbar palsies with hypokinetic speech and dysphagia
  • Psychiatric manifestations – behavioral disturbances, depression, hallucinations, paranoia
    • Frequently occur prior to hepatic and neurologic symptoms
  • Other
    • Hemolytic anemia
    • Musculoskeletal – arthritis, osteoporosis
    • Renal – nephrolithiasis, aminoaciduria
    • Cardiac – cardiomyopathy, arrhythmias
    • Endocrine – hypoparathyroidism, infertility

Treatment

  • Prompt diagnosis is important since the treatment requires 3-6 months for the desired effect; goal of therapy is to reduce copper accumulation
  • Untreated Wilson disease can be fatal, subsequent to fulminant liver failure and/or brain damage