Overview
Recognise hepatic and neuropsychiatric Wilson disease, combine imperfect copper tests and deliver lifelong specialist decoppering without losing an acute transplant window.
ATP7B is required for hepatocytes to export excess copper into bile. When both alleles are pathogenic, copper accumulates and eventually spills into blood and extrahepatic tissues. Liver manifestations range from steatosis or incidental transaminase elevation through chronic hepatitis and cirrhosis to fulminant failure. Neurological disease can produce tremor, dystonia, dysarthria, parkinsonism, ataxia or drooling, while psychiatric change includes depression, disinhibition, cognitive decline or psychosis. The breadth of presentation and lack of one definitive screening result account for diagnostic delay.
A structured assessment uses the Leipzig concept but preserves clinical judgement. Low caeruloplasmin, Kayser-Fleischer rings, increased twenty-four-hour urinary copper, ATP7B variants and increased hepatic copper each add evidence. Total serum copper can be low because caeruloplasmin-bound copper falls, even while toxic exchangeable copper is high. Acute liver failure distorts several tests. Genetic analysis may find two pathogenic variants but can be inconclusive; quantitative hepatic copper is useful when uncertainty remains, although sampling variation and cholestasis can mislead.