- AR. Mutations in the ATP7B gene on C13
- Total body copper is increased, excess copper deposited and causes damage to several organs
Pathophysiology
- Normally diet copper is absorbed from the stomach and proximal SI
- ATP7B function
- Links Cu to ceruloplasmin to release it into the blood
- Removes excess Cu by secreting it into the bile
- In WD there is a failure of copper incorporation into ceruloplasmin and secretion into bile
- Causes Cu to accumulate in liver, basal ganglia, eyes, kidney, skeleton
Clinical features
Liver disease
- Acute hepatitis – MC in children
- Fulminant liver failure – liberation of free Cu in bloodstream causes massive hemolysis and renal tubulopathy
- Cirrhosis, portal HTN
Neurological disease
- Extra-pyramidal symptoms (EPS) – tremor, choreoathetosis, dystonia, parkinsonism, dementia
- Clumsiness
- Kayser-Fleischer
- Most characteristic feature
- Greenish-brown discoloration on corneal margin
Diagnosis
- ↓serum ceruloplasmin (<140μmol/l pathognomonic) + serum copper
- Slit lamp – descemet membrane
- ↑urine copper – measure 24 hr urinary copper excretion whilst giving D-pencillamine
- >25μmol/24hrs – diagnostic
Treatment
- Pencillamine – 1.5g/day
- Liver transplant – for Fulminant liver failure, cirrhosis
- Liver damage is reversible if pre-cirrhotic .