Wilson's disease

• autosomal recessive; defect of ATP7B on chromosome 13
• affected younger individuals aged 5 to 40 years
• reduce the formation and secretion of ceruloplasmin and decrease the secretion of copper into the biliary system
• Copper is pro-oxidant, so accumulation of it in liver damage hepatic tissue through the generation of free radicals
• Eventually copper leaks from injured hepatocytes into blood to be deposited in various tissues, including the basal ganglia (hepatolenticular degeneration) and cornea; Atrophy of the basal ganglia then ensues
• 10% have psychosis and delusions - not the encephalopathic features or delirium that you would get with any form of liver failure
• Parkinsonian-like tremor, rigidity, ataxia, slurred speech, drooling, personality changes, depression, paranoia, and catatonia
• Kidneys ⇒ type 2 RTA

Dx

Scenario: A patient presents with choreoathetoid movements and psychosis gives the clue to perform the slit-lamp examination. KayserFleischer rings are then found, confirming the diagnosis of Wilson disease.

1. Coombs negative hemolytic anemia
2. The best initial test is a slit-lamp exam - Kayser-Fleicher rings
3. Low Ceruloplasmin
4. The most accurate test is looking at an abnormally increased amount of copper excretion in to the urine after giving penicillamine
   • 24-hour urine copper excretion >40 mcg
5. Liver biopsy (more sensitive and specific) Gold standard
   • mild to moderate inflammation, portal fibrosis, and hepatocyte necrosis
   • macrovesicular steatosis, vacuolated hepatocellular nuclei, and mallory bodies

Indications for liver biopsy --

1. Patients with decreased ceruloplasmin (<5mg/dL) without Kayser-Fleischer rings and
   • abnormal liver function tests or
   • 24-hour urine copper excretion > 40 mcg
2. Patients with normal serum ceruloplasmin and Kayser-Fleischer rings