Wilson Disease

Snapshot

• A 33-year-old female is referred to a neurologist by her primary care physician for unsteady gait, forgetfullness, and recent episodes of Terret-like spells where she will fling one arm out and above her head seemingly unprovoked. On physical exam, the neurologist notices that her irises appear multicolored with concentric rings around the perpiphery. He is concerned for a metabolic disease and orders several laboratory and radiologic studies. In the interim he has advised her to avoid eating chocolate and shellfish. 

Introduction

• Free copper accumulation in many tissues (liver, brain, cornea, joints) 
  • also known as hepatolenticular degeneration
  • mutation in ATP7B results in
    • inadequate copper excretion by liver into bile  
    • failure of copper to enter circulation bound to ceruloplasmin
      • ceruloplasmin is the transport protein for copper (like transferrin for Fe)
      • copper bound to ceruloplasmin normally represents the largest fraction of copper in the body
  • free copper generates free radicals that damage tissues
  • see Metabolism of copper topic 
• AR inheritance

Presentation

• Symptoms
  • Parkinson-like symptoms
    • secondary to copper desposits in putamen
  • hemiballismus
    • secondary to copper desposits in subthalamic nucleus
  • dementia
    • secondary to copper desposits in cerebral cortex
• Physical exam
  • cirrhosis
  • corneal deposits on slit lamp examination 
    • Kayser-Fleischer rings  
• RARELY seen in other conditions that may result in increased copper such as primary billiary cirrhosis

Evaluation

• Labs 
  • ↓ total serum copper
    • due to ↓ ceruloplasmin
  • ↑ serum non-ceruloplasmin bound copper
  • ↑ urine/serum free copper
  • hemolytic anemia
• Liver Biopsy
• If performed will show increased hepatic copper

Treatment

• Medical
  • ammonium tetrathiomolybdate
    • facilitates urinary excretion of copper
  • penicillamine 
    • copper chelating agent
  • trientine
    • copper chelating agent
  • zinc
    • competes with copper for absorbtion in the gut via the same transporter
• Surgical
• Consider liver transplantation as clinical condition deteriorates 

Prognosis, Prevention, and Complications

• At risk for liver disease
  • hepatitis
  • cirrhosis
  • carcinoma (hepatocellular)
• Also at risk for Fanconi’s disease of the proximal tubules