Wilson’s disease

Wilson’s disease

Introduction

Wilson’s disease is a rare autosomal recessive genetic disorder characterised by defective copper metabolism, leading to the accumulation of copper in various tissues — primarily the liver, brain, eyes (corneas), and kidneys. Without treatment, this copper overload causes progressive damage to multiple organ systems.

Peak Incidence

  • Most commonly presents between 10 and 25 years of age.

Pathophysiology

  • Caused by mutations in the ATP7B gene, leading to impaired copper transport and reduced incorporation of copper into caeruloplasmin.
  • Copper accumulates first in the liver and then disseminates to other organs, causing hepatic, neurological, and psychiatric manifestations.
  • Excess free copper can also cause intravascular haemolysis and renal tubular dysfunction.

Symptoms

Hepatic Symptoms

  • Chronic hepatitis (present in ~40% of cases).
  • Cirrhosis (may develop over time).
  • Ascites and splenomegaly (due to portal hypertension).
  • Acute liver failure in severe cases.

Neurological Symptoms (~50% of cases)

  • Parkinsonism: tremor, bradykinesia, rigidity.
  • Dysarthria (slurred or difficult speech).
  • Dystonia (abnormal muscle tone and posturing).
  • Chorea (involuntary jerky movements).
  • Cognitive decline and dementia.
  • Motor symptoms may be asymmetrical.

Psychiatric Symptoms (~10% of cases)

  • Depression.
  • Mood disturbances and irritability.
  • Personality changes and, in some cases, psychosis.

Signs

Hepatic

  • Hepatomegaly.
  • Jaundice.
  • Ascites.
  • Splenomegaly.

Neurological

  • Tremor.
  • Rigidity and bradykinesia.
  • Dystonia.
  • Asterixis (flapping tremor).
  • Ataxia.
  • Cognitive impairment.

Psychiatric

  • Features such as depression, personality change, or psychosis.

Other

  • Kayser-Fleischer rings – green-brown copper deposits at the corneal margins (seen on slit-lamp examination).
  • Haemolytic anaemia – due to free copper-induced red cell destruction.
  • Renal tubular dysfunction – may lead to Fanconi syndrome.
  • Osteoporosis and pathological fractures.

Diagnosis

Copper Studies (Mainstay of Diagnosis)

  • Low serum caeruloplasmin – a copper-binding protein that is usually reduced in Wilson’s disease.
  • 24-hour urinary copper excretion – elevated levels support the diagnosis.
  • Low total serum copper but increased free (non-caeruloplasmin-bound) copper.

Blood Tests

  • FBC – may show haemolytic anaemia:
    • Low haptoglobin.
    • Elevated reticulocyte count.
    • Raised unconjugated bilirubin.
  • Liver function tests (LFTs):
    • Mixed hepatocellular-cholestatic picture.
    • AST/ALT raised (often higher than ALP).
    • GGT may be elevated.
    • ALP may appear disproportionately low in acute liver failure.

Additional Investigations

  • Genetic testing – confirms mutations in the ATP7B gene (gold standard for definitive diagnosis).
  • Liver biopsy – may show hepatic copper accumulation (>250 µg/g dry weight).
  • MRI brain – may reveal basal ganglia changes. The “face of the giant panda” sign is a rare but characteristic finding.
  • Slit-lamp examination – to identify Kayser-Fleischer rings.
  • Coombs test – negative in haemolytic anaemia caused by Wilson’s (non-immune).
  • Blood film – may show spherocytes or schistocytes.

Complications

  • Cirrhosis and decompensated liver failure.
  • Hepatocellular carcinoma (rare but possible).
  • Irreversible neurological deterioration.
  • Psychiatric morbidity and reduced quality of life.
  • Haemolytic anaemia.
  • Renal impairment.
  • Osteoporosis and fractures.

Management

Copper Chelation Therapy

  • Penicillamine – first-line chelating agent (monitor for adverse effects).
  • Trientine hydrochloride – alternative chelator, used if penicillamine is not tolerated.

Zinc Therapy

  • Zinc salts – inhibit intestinal copper absorption and are used for maintenance therapy after copper depletion.

Dietary Modifications

  • Avoid high-copper foods: shellfish, liver, nuts, chocolate, mushrooms, and copper-containing supplements.

Liver Transplantation

  • Considered in acute liver failure or decompensated cirrhosis unresponsive to medical therapy.

Symptomatic Management

  • Neurological: Physical therapy, speech therapy, and medications for tremor or dystonia.
  • Psychiatric: Antidepressants, mood stabilisers, or antipsychotics as appropriate.
  • Occupational therapy to support daily living.

Monitoring

  • Regular monitoring of:

    • Liver function tests.
    • 24-hour urinary copper excretion.
    • Serum free copper.
    • Neurological and psychiatric status.

FAQ from our users

What is the genetic inheritance of Wilson’s disease?
  • Autosomal recessive.
  • Caused by mutations in the ATP7B gene on chromosome 13.
  • The gene is responsible for removing excess copper from the body via bile excretion.
  • Without this, copper builds up in the body.
Why can Wilson’s cause Parkinson-like symptoms?
  • Copper deposits accumulate in the basal ganglia, particularly in the putamen and globus pallidus, leading to motor dysfunction.
What is serum caeruloplasmin?
  • A copper-transporting protein in the blood.
  • Low levels suggest Wilson’s disease but can be falsely normal or elevated in certain conditions (e.g., cancer, chronic inflammation).

Common pitfalls in a clinical setting

Common pitfalls in a clinical setting
  • Wilson’s disease can present with vague symptoms like psychiatric changes, mild tremor, or liver dysfunction.
  • Consider Wilson’s disease in patients with unexplained liver or neurological symptoms between 10–25 years.
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