Harvey's Garden

Wilson disease

2 min read

  • Impaired copper excretion causes copper to accumulate in the body.
  • Early-stage Wilson disease is characterized by the presence of copper deposits in the liver.
  • As the disease progresses, copper accumulates in other organs as well, most importantly in the brain and cornea.

Epidemiology

Etiology

Pathophysiology

Tip

  • Apoceruloplasmin
    • Copper-free precursor synthesized in liver.
    • Unstable half-life; degrades rapidly if not loaded with copper.
  • Ceruloplasmin
    • Copper-bound form (loaded by ATP7B in Golgi).
    • Stable half-life; carries 95% of circulating copper.
    • Ferroxidase activity (links Cu metabolism to Fe metabolism).
  • Autosomal Recessive mutation of ATP7B gene on Chromosome 13.
  • Defect in hepatocyte copper-transporting ATPase (ATP7B protein).
  • Primary Defects:
    1. Inability to excrete excess copper into bile (main route of excretion).
    2. Failure to incorporate copper into apoceruloplasmin to form functional ceruloplasmin.
  • Consequences:
    • ↓ Serum ceruloplasmin (due to shorter half-life of apoceruloplasmin).
    • ↑ Free (unbound) serum copper.
    • Accumulation of toxic copper levels in tissues via Fenton reaction (oxidative damage).
  • Tissue Deposition Sequence:
    • Liver: Accumulates first → hepatocyte necrosis → micronodular cirrhosis.
    • Brain: Deposits in Basal Ganglia (specifically Putamen and Globus Pallidus) → parkinsonism, dysarthria, tremor.
    • Cornea: Deposits in Descemet membrane → Kayser-Fleischer rings.
    • Kidneys: Proximal tubule damage → Fanconi syndrome.

Tip

Don’t mess up with Hemochromatosis

Clinical features

  • Neurological
    • Cerebellar symptoms, e.g.:
      • Dysarthria (most common)
    • Extrapyramidal symptoms, e.g.:
      • Dystonia
      • Parkinsonism
      • Tremor (usually asymmetric, affecting the hands), which may be any combination of:
        • Resting tremor
        • Intention tremor
        • Wing-beating tremor: a low frequency, high amplitude tremor that is most prominent when the arms are outstretched anteriorly or laterally
    • Drooling (caused by oropharyngeal dysphagia)
    • Cognitive impairment

Wilson disease vs hemochromatosis

  • Wilson disease has neurologic symptoms but hemochromatosis doesn’t have
  • Think about Wilson from Don’t Starve, the mad scientist

Diagnostics

Treatment

General principles

  • Encourage a low-copper diet (e.g., avoidance of organ meats, shellfish, nuts, chocolate, copper-containing dietary supplements).
  • Refer patients with refractory decompensated cirrhosis or acute liver failure for liver transplantation.

Pharmacological therapy

  • First line: chelating agents, e.g., penicillamine (preferred) or trientine
    • Chelating agents facilitate renal excretion of copper by forming water-soluble compounds.
    • Adverse effect: Membranous nephropathy
  • Maintenance therapy: reduced-dose zinc salts or a chelating agent

Graph View

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