| What is Wilson's disease? | Inborn error of copper metabolism, increased copper accumulation in tissues as a result of decreased hepatobiliary excretion of copper.
AKA Lenticular Degeneration.
worldwide 1 -30,000 / described by K.Wilson in 1912 |
| What is copper? | Trace metal ion and essential cofactor for many enzymes and proteins.
Plays a fundamental role in NS biochemistry, toxic in excess, dialy intake is 1-2 mg, 50% of them are absorbed by small intestine |
| What is the genetic link of wilson's disease? | Autorecessive, WD gene (ATP7B mutated on long arm of chromosome 3) which encodes copper transporting P-type ATPase which is expressed in liver. |
| How is the pathophysiology of Wilson's disease? | Hepatic copper transport disorder, copper accumulates in liver and other organs (brain and cornea) followed by hepatic/neurological symptoms due to copper toxicity.
Molecular mechanism is poorly understood, Wilson Disease Protein has two functions facilitate Cu export from cell and deliver Cu to secretory pathways incorporation w/Cu dependent enzymes. |
| What are the symptoms of Wilson's disease? | Hepatic (acute hepatitis to failure)
Neuro (movement disorders, drooling, seizures, migraines, insomnia)
Psychiatric (depression, neurosis, personality change, psychosis)
Others (kidney, skeletal, thyroid, heart, pancreas and gynco, fever, jaundice, SoB, fatigue, stiff limbs, abdominal and bone pain, hemolytic anemia) |
| How is the clinical presentation of Wilson's disease? | Diverse presentations of hepatic WD, most pt are young, symptoms appear at age 6.
We see Kayser-Fleischer Rings (KF- in eyes), persistent hepatomegaly/elevation of AST (first sign), jaundice w/out cause, acute hepatitis (w/non specific autoantibodies and IgG), non-alcoholic fatty liver (misdiagnosed as steatosis) |
| How is dx of WD? | Cu and Ceruloplasmin measure (normal Cu 10-22, Wilson's high in liver >250micg/g on biopsy and serum ceruloplasmin low (below 200-600))
LFT (depends if we have hemolytic anemia ->AST elevated, if cirrhosis (ALP and Bi elevated, progress to liver failure Prothrombin time elevated)
Urinary Cu (24-hour excretion >40 micromol)
Challenge w/penicillamine (increase Cu in urine after 24-hour 200-500mg)
Slit-lamp exam of eye (See KF rings, nearly always present and associated w/neuro presentation, absence doesn't exclude the disease)
Liver biopsy (definitive wide section (not diffuse Cu accumulation), Cu>250 micg/g diagnostic) |
| How is tx of WD? | Dietary (avoid liver, shellfish (mushrooms,nuts chocolote are conroversial), intake vitamin B6, water purification)
Drugs (Reduce Cu storage (penicillamine [chelates Cu- no longer used due to side effects] or trientine HCL [complexes in blood and kidney eliminated by liver])
Reduce intestinal absorption (Zn acetate/Zn sulphate compete w/carrier protein metallothionine) |
