Wilson's Disease Flashcards
What is Wilson’s disease?
A rare (3/100000) inherited disorder of copper excretion with excess depositions in liver and CNS (e.g. basal ganglia)
It is a treatable condition so everyone with cirrhosis should be screened.
Genetics of Wilson’s disease.
Autosomal recessive disorder of a copper transporting ATPase called ATP7B.
Pathophysiology of Wilson’s disease
Total body copper content is around 125mg.
In the liver copper is incorporated into caeruloplasmin. The caeruloplasmin is then released into the bloodstream in order to transport copper into distant organs, such as the CNS. It is also excreted into bile when there is an excess.
In Wilson’s disease due to the dysfunction of copper transporting ATPase ATP7B copper cannot be incorporated into caeruloplasmin, and cannot adequately be secreted into bile.
This leads to caeruloplasmin being released into the blood without the copper, and is degraded very quickly.
The copper accumulates in the liver and also other organs later on. This is very destructive causing liver damage.
The deficiency of copper also causes other problems as well.
Clinical presentation of Wilson’s disease.
Children;
Liver disease (hepatitis, cirrhosis, fulminant liver failure)
Young adults;
CNS signs such as tremors, dysarthria, dysphagia, dyskinesias, dystonias, dementia, parkinsonism and ataxia
There can also be mood disturbances such as depression/mania, labile emotions and dysregulated libido +/- personality changes.
Cognition can be decreased with memory loss, low IQ and issues with problem solving.
Haemolysis, blue lunulae (nails), arthritis, grey skin and hypermobile joints.
What is a defining feature of Wilson’s disease?
Kayser-Fleischer (KF) Rings
Tests done in Wilson’s disease.
Urine - 24h copper excretion (expect this to be high)
>100 mcg/24h where normal is < 40mcg/24h
Increased LFTs
Low serum copper <11mcgmol/L
Low serum ceruloplasmin < 200mg/L
Molecular genetic testing is diagnostic
Slit lamp exam - KF rings
Liver biopsy showing increased hepatic copper, hepatitis and cirrhosis
MRI
MRI findings in Wilson’s disease
Degeneration of basal ganglia, fronto-temporal, cerebellar and brainstem.
When else might serum ceruloplasmin be low?
In protein deficiency states like nephrotic syndrome, malabsorption and malnutrition
Management of Wilson’s disease.
Diet
Drugs
Liver transplant
Screening of siblings (asymptomatic homozygotes needs treatment)
Diet management in Wilson’s disease.
Avoid foods with high copper content.
Check water sources to not include copper like wells and pipes.
Foods with high copper contents.
Liver
Chocolate
Nuts
Mushrooms
Legumes
Shellfish
Drug treatment of Wilson’s disease.
Lifelong penicillamine (500 mg/6-8h PO for 1 year, then 0.75-1g/d PO after)
Side effects of penicillamine.
Nausea
Rash
Low WCC
Low Hb
Low platelets
Haematuria
Nephrosis
Lupus
Monitor FBC and urinary copper as well as protein excretion with treatment.
Indications of liver transplantation in Wilson’s disease.
In severe disease
Prognosis of Wilson’s disease.
Pre-cirrhotic liver disease is reversible.
CNS damage is not as reversible
There are no clear clinical prognostic factors.
Fatal events include liver failure, bleeding and infection.
