Wilson's disease Flashcards
What is Wilson’s disease?
Wilson’s disease = Hepatolenticular degeneration = autosomal recessive disorder characterised by decreased biliary excretion of copper and accumulation in the liver and brain (especially basal ganglia)
ATP7B gene part of the biliary excretion of copper pathway
What is the aetiology of Wilson’s disease?
Autosomal recessive condition
o Gene responsible is on C13 and codes for copper-transporting ATPase in hepatocytes (ATP7B)
Over 250 mutations discovered – most patients heterozygotes
o Mutations interfere with transport INTO the IC compartments for incorporation into caeruloplasmin or bile excretion
o Excess copper damages hepatocyte mitochondria, causing cell death, releasing free copper into the plasma which is then deposited into other tissues
What is the epidemiology of Wilson’s disease?
Rare
o Carried by 1 in 100
o Prevalent in 1 in 30,000
Patients usually 10-40 years old, presenting with hepatic disease or movement disorder
What are the symptoms of Wilson’s disease?
Liver o Hepatitis, LF, cirrhosis o Jaundice o Easy bruising o Variceal bleeding o Encephalopathy
Neurological - DANISH o Dyskinesia o Ataxia o Nystagmus o Intention tremor o Slurred speech (dysarthria) o Hypotonia
o Rigidity
o Dysphagia
o Drooling
o Dementia
Psychiatric
o Conduct disorder
o Personality changes
o Psychosis
What are the signs of Wilson’s disease?
Liver
o Hepatosplenomegaly, jaundice, ascites/oedema, gynaecomastia
Neurological
o Rigidity, tremor, dystonia
Eyes
o Green/brown Kayser-Fleischer ring at the corneal limbus
o Sunflower cataract
What are the investigations for Wilson’s disease?
24 hour urinary copper levels = increased >100micrograms
Bloods
o LFTs: raised AST, ALT, AlkPhos - Always abnormal in hepatic presentation
o Serum caeruloplasmin (may be F+ as acute phase protein): Low
Liver biopsy
o Increased copper content
Slit lamp examination
o Kayser-Fleischer rings present in 99% of neurologically symptomatic
Genetic ATP7B mutation tests
MRI
o Basal ganglia lesion
