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Wilson's Disease

Summary

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  • Autosomal recessive disorder of copper metabolism
  • Characterised by excessive copper accumulation in various organs, primarily liver and brain
  • Imaging findings include basal ganglia abnormalities and hepatic cirrhosis1

Pathophysiology

  • Caused by mutations in ATP7B gene on chromosome 13
    • Impaired biliary copper excretion
    • Reduced incorporation of copper into ceruloplasmin
  • Results in toxic accumulation of copper in liver, brain, cornea, and other organs

Demographics

  • Worldwide prevalence: 1 in 30,000 to 1 in 100,000
  • No gender predilection
  • Higher prevalence in certain populations (e.g., Sardinia, Eastern Asia)

Diagnosis

  • Clinical presentation:
    • Hepatic dysfunction
    • Neurological symptoms (e.g., tremor, dysarthria, dystonia)
    • Psychiatric disturbances
    • Kayser-Fleischer rings in cornea
  • Laboratory findings:
    • Low serum ceruloplasmin
    • Elevated 24-hour urinary copper excretion
    • Elevated hepatic copper concentration on liver biopsy
  • Genetic testing for ATP7B mutations

Imaging

  • MRI:
    • Bilateral symmetric T2/FLAIR hyperintensity in the putamen, globus pallidus, caudate, thalamus and midbrain/pons
    • "Face of the giant panda" sign in the midbrain (and a "panda cub" in the pons)
    • T1 hyperintensity of the globus pallidus (from associated liver disease/manganese)
    • SWI hypointensity from copper and iron deposition
    • Generalised and brainstem atrophy in chronic disease

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  • A 25-year-old male presented 6 months prior with dysarthria, dystonia and cirrhosis.
  • Imaging showed patchy hyperintensity in the deep grey nuclei and brainstem.
  • SWI showed hypointensity in the globi pallidi.

Treatment

  • Copper chelation (penicillamine/trientine) and zinc; liver transplantation for hepatic failure. The "face of the giant panda" midbrain sign is the classic imaging clue

Differential diagnosis

Differential Diagnosis Differentiating Feature
Acquired hepatocerebral degeneration Bilateral symmetric T1 hyperintensity of globi pallidi; T2 hyperintensity in basal ganglia and white matter; no SWI hypointensity in copper-specific distribution
Leigh disease Symmetric T2 hyperintensity in basal ganglia and brainstem periaqueductal grey; putamen and caudate involvement; no SWI hypointensity
Japanese encephalitis / flaviviral encephalitis Bilateral thalamic and basal ganglia T2 hyperintensity; may show haemorrhage and restricted diffusion

  1. Bandmann et al. Wilson's disease and other neurological copper disorders. 2015. The Lancet. Neurology - Open in new tab. ↩