= hepatolenticular degeneration. Autosomal recessive condition with copper accumulation due to impairment of biliary excretion. Leads to cirrhosis, via a stage indistinguishable from chronic active hepatitis, plus neurological disease. Caused by mutations of the ATP7B gene that codes for a copper transporting ATPase – over 300 mutations known, varying geographically.

Clinical Presentation

Usually presents in late teens but has been described as young as 3yrs. Neurological presentation tends to be older (by 5 years) although they usually have subclinical liver disease. Hepatic disease varies from elevated aminotransferases, through chronic liver disease to fulminant hepatic failure (often with Coombs negative haemolytic anaemia), about 5% of presentations.

Basal ganglia involvement leads to movement disorders viz:

• Tremor
• Chorea
• Parkinsonism
• Gait disturbances
• Dysarthria

Other neurological signs are:

• Psychiatric symptoms
• Depression
• Neuroses
• Personality changes
• Psychosis

It can also cause:

• Epilepsy
• Sunflower cataracts
• Aminoaciduria
• Renal stones
• Osteomalacia with spontaneous fractures

Diagnosis

Can be tricky given multisystem disorder and limited sensitivity/specificity of tests. Heterozygotes may also have borderline results. If typical presentation then diagnosis can be made on basis of:

• Kayser-Fleischer rings
• Low serum ceruloplasmin levels (<0.2g/L)
• Genetic screening of limited utility due to number of known mutations

May require extensive tests of copper metabolism especially with severe hepatic presentation, where up to 50% can have normal ceruloplasmin (an acute phase reactant) eg

• Non-caeruloplasmin-bound serum copper
• 24-h urinary copper excretion – can be abnormal in other chronic liver diseases, however. Excretion of >25micromol/24hr after penicillamine is a diagnostic test in children.
• Liver copper content (>250mcg/g dry weight) – best test when others ambiguous.

In fulminant hepatic failure the following features may suggest diagnosis:

• Haemolysis (Coombs negative)
• Alkaline phosphatase surprisingly low viz ALP:Bilirubin ratio of less than 1 has 86% sensitivity and 50% specificity in children

Treatment

• Diet – chocolate, liver, nuts, mushrooms, and shellfish are high in copper
• Zinc – reduces copper absorption from gut. Monotherapy is an option for maintenance therapy.
• Chelation
  • D-penicillamine – but note side effects, and some patients with neurological disease deteriorate on starting treatment
  • Trientine – perhaps less side effects
• Liver transplantation – curative, except for long-standing neurological disease. Indicated for fulminant hepatic failure.

Monitoring

• Neurological function
• Liver function tests
• 24hr urinary copper excretion (aim for less than 2 micromol/d)
• Non-ceruloplasmin bound copper of 50-150mcg/L