Wilson's disease

Incidence - very rare

Age - children and young adults

Sex

Geography - occurs worldwide
- highest prevalence in countries where consanguinuity is common

Aetiology
- copper is normally absorbed from the stomach and upper small intestine, transported into the liver bound to albumin, incorporated into caeruloplasmin, and secreted into the blood
- copper is normally excreted in the bile

- autosomal recessive inborn error of copper metabolism
- defect of copper-transporting ATP-ase encoded by a gene on chromosome 13
- there are over 60 different mutations
- copper is deposited in the liver, basal ganglia and cornea
- there is a failure of biliary excretion of copper
- there is usually a low caeruloplasmin due to poor synthesis

Presentation
Children
- usually present with hepatic problems
- episodes of acute hepatitis
- can go on to fulminant hepatic failure, chronic hepatitis or cirrhosis

Young adults
- present with neurological disturbances - akinetic-rigid syndrome, dyskinesias, progressive intellectual impairment
- tremor, dysarthria, involuntary movements, eventually dementia

- signs of liver disease with signs of Basal ganglia involvement
- Kayser-Fleischer rings - copper deposition in cornea just within corneoscleral junction

Investigations
Serum copper and caeruloplasmin
- usually reduced; may be normal

Urinary copper
- usually increased

Liver biopsy
- high levels of copper in the liver are also seen in prolonged cholestasis
- measurement of ⁶⁴Cu into the liver may be helpful

FBC
- evidence of haemolysis and anaemia my be present

Macro

Micro - ranges from chronic hepatitis to macronodular cirrhosis
- periportal distruibution of copper
- damage to and cavitation of basal ganglia
- tubular degeneration of kidneys
- erosions in bones

Staging

Serum markers

Management
- lifelong penicillamine treatment 1-2 g daily - chelates copper
- urine copper levels should be monitored and dose adjusted accordingly
- serious side-effects include skin rashes, leucopenia, renal damage (10%)

Screen all siblings and children of patients; if any show signs of copper accumulation, they should be treated regardless of whether they are symptomatic

Prognosis - neurological damage is permanent
- FHF or decompensated cirrhosis should be treated with liver transplantation

Complications

Hepatobiliary medicine

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Incidence	- very rare
Age	- children and young adults
Sex
Geography	- occurs worldwide - highest prevalence in countries where consanguinuity is common
Aetiology	- copper is normally absorbed from the stomach and upper small intestine, transported into the liver bound to albumin, incorporated into caeruloplasmin, and secreted into the blood - copper is normally excreted in the bile - autosomal recessive inborn error of copper metabolism - defect of copper-transporting ATP-ase encoded by a gene on chromosome 13 - there are over 60 different mutations - copper is deposited in the liver, basal ganglia and cornea - there is a failure of biliary excretion of copper - there is usually a low caeruloplasmin due to poor synthesis
Presentation	Children - usually present with hepatic problems - episodes of acute hepatitis - can go on to fulminant hepatic failure, chronic hepatitis or cirrhosis Young adults - present with neurological disturbances - akinetic-rigid syndrome, dyskinesias, progressive intellectual impairment - tremor, dysarthria, involuntary movements, eventually dementia - signs of liver disease with signs of Basal ganglia involvement - Kayser-Fleischer rings - copper deposition in cornea just within corneoscleral junction
Investigations	Serum copper and caeruloplasmin - usually reduced; may be normal Urinary copper - usually increased Liver biopsy - high levels of copper in the liver are also seen in prolonged cholestasis - measurement of ⁶⁴Cu into the liver may be helpful FBC - evidence of haemolysis and anaemia my be present
Macro
Micro	- ranges from chronic hepatitis to macronodular cirrhosis - periportal distruibution of copper - damage to and cavitation of basal ganglia - tubular degeneration of kidneys - erosions in bones
Staging
Serum markers
Management	- lifelong penicillamine treatment 1-2 g daily - chelates copper - urine copper levels should be monitored and dose adjusted accordingly - serious side-effects include skin rashes, leucopenia, renal damage (10%) Screen all siblings and children of patients; if any show signs of copper accumulation, they should be treated regardless of whether they are symptomatic
Prognosis	- neurological damage is permanent - FHF or decompensated cirrhosis should be treated with liver transplantation
Complications