AKT · Endocrine/Lipids, metabolic & inheritedlow yield

Wilson disease

Autosomal-recessive copper overload (ATP7B defect)

Overview

Autosomal-recessive defect of copper excretion (ATP7B) causing copper accumulation in liver, brain and eyes. Presents in young people (children–30s) with liver disease (hepatitis/cirrhosis/acute liver failure) and/or neuropsychiatric features (tremor, dystonia, dysarthria, parkinsonism, personality/psychiatric change). Kayser-Fleischer rings, low caeruloplasmin; treated with copper chelation. (Also a neurology/GI differential.)

Recognise

Young patient with unexplained LIVER disease (hepatitis, cirrhosis, fulminant failure) and/or NEUROPSYCHIATRIC features (tremor, dysarthria, dystonia, parkinsonism, mood/behaviour change)
KAYSER-FLEISCHER RINGS (copper at the corneal limbus — slit lamp)
Low serum caeruloplasmin, raised urinary copper, raised hepatic copper; Coombs-negative haemolysis

Red flags

Acute (fulminant) liver failure in a young person → consider Wilson's (may need transplant)
Untreated neurological disease progresses — early treatment is key

Differentials & how to tell them apart

HaemochromatosisIRON (not copper) overload, older patient, bronze skin/diabetes, high ferritin/transferrin saturation

Autoimmune/viral hepatitisserology; no copper handling abnormality

Parkinson's / other movement disordersolder, no liver disease or KF rings, normal copper studies

Investigations

Low caeruloplasmin, high 24-h urinary copper, slit-lamp for Kayser-Fleischer rings; liver biopsy (hepatic copper); genetics; MRI brain (basal ganglia).

Management

Copper chelation (penicillamine/trientine) ± zinc; low-copper diet

1Suspect in any young person with unexplained liver disease and/or movement/psychiatric disorder. Confirm (caeruloplasmin, urinary copper, KF rings, genetics). Start copper chelation (penicillamine or trientine), or zinc.Gate: Consider Wilson's in young (<40) unexplained liver disease OR a new movement/psychiatric disorder — it is treatable and progressive if missed; fulminant liver failure may need urgent transplant
2Lifelong chelation/zinc and low-copper diet; monitor copper indices and liver/neurological status; family screening; transplant for liver failure.

Copper chelation (penicillamine or trientine) — first-line — promotes copper excretion

Zinc — reduces copper absorption (maintenance/adjunct)

Low-copper diet; liver transplant — diet adjunct; transplant for fulminant failure/decompensated cirrhosis

Key points

Young + liver disease + neuropsychiatric features + Kayser-Fleischer rings + low caeruloplasmin = Wilson's. Treatable copper overload — the inherited-metabolic counterpart to haemochromatosis (iron). (Cross-references neurology/GI.)

Monitor & prognosis

Copper studies; liver/neuro status; adherence.

Good if treated early; progressive if missed.

Source: EASL; BSG