Wilson’s Disease

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1- Definition

2- Pathophysiology

3- Clinical Features

4- Investigations

5- Management

6- Prognosis

Introduction

Wilson’s disease is a rare autosomal recessive disorder of copper metabolism, caused by mutations in the ATP7B gene, leading to toxic copper accumulation in the liver, brain, eyes, and kidneys.

Pathophysiology

  • ATP7B encodes a copper-transporting ATPase vital for:

    • Excretion of copper into bile

    • Incorporation into caeruloplasmin (copper-binding protein)

  • Defect → copper not excreted → accumulates in tissues

  • Liver affected first, followed by brain (basal ganglia), eyes, skeleton, and kidneys

  • Over 700 mutations; most patients are compound heterozygotes

Clinical Features

Age of onset: 5–45 years

A. Liver Disease (childhood/adolescence)

  • Elevated LFTs (asymptomatic)

  • Acute hepatitis

  • Jaundice, hepatomegaly

  • Fulminant liver failure (esp. young women)

    • Causes haemolysis + renal tubular injury

  • Clue: Liver disease + haemolytic anaemia in <40 years

B. Neurological Disease (late adolescence)

  • Movement disorders:

    • Tremor, dystonia, parkinsonism, choreoathetosis

  • Neuropsychiatric features:

    • Behavioural changes, dementia

  • Occurs after or with liver disease

C. Kayser–Fleischer Rings

  • Green-brown corneal rings from copper in Descemet’s membrane

  • Present in:

    • ~60% of adults

    • Nearly all with neurological disease

  • Best seen with slit-lamp

  • Disappear with treatment

Kayser-Fleischer ring

Investigations

–Biochemical tests

  • ↓ Serum caeruloplasmin (best initial clue, but not always low)

  • ↑ Free serum copper

  • ↑ 24-hr urinary copper >0.6 µmol (38 µg)

  • D-penicillamine challenge: >25 µmol/24 hr = diagnostic

  • ↑ Hepatic copper on liver biopsy

–Genetic testing

  • Not routine due to variability but useful in family screening

Management

Lifelong copper-chelation therapy:

  • First-line:

    • D-penicillamine (1–4 mg/day)

      • Monitor for: rash, nephropathy, lupus-like syndrome, marrow suppression

  • Alternatives:

    • Trientine

    • Zinc salts – reduce absorption of dietary copper

–Important:

  • Never stop therapy abruptly → may cause acute liver failure

  • Treat asymptomatic siblings after screening

-Liver transplantation:

  • Indicated in:

    • Fulminant hepatic failure

    • Decompensated cirrhosis

  • Role in severe neurological disease unclear

Prognosis

  • Excellent if diagnosed early and treated

  • Presymptomatic patients can live normal lives

 

  • Late diagnosis or treatment interruption → irreversible liver or brain damage

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