Fact-sheet: Wilson disease
Updated on 03/31/2020 at 9:32 AM
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Definition
Genetic disease characterized by systemic copper overload.
Clinical features
Epidemiology:
- prevalence 1/100,000
- autosomal recessive inheritance, heterozygous carrier prevalence 1/90
Manifestations:
Overload is initially hepatic, then systemic once hepatic storage capacity is exceeded.
Onset in children at age 15 (isolated hepatic form) or 25-30 years (neuropsychiatric form), exceptional onset after age 35.
- Hepatic: hepatomegaly, acute liver failure, cirrhosis.
- Neurologic: parkinsonian syndrome, postural and intention tremor, focal or generalized dystonia, cerebellar disorders.
- Psychiatric: behavioral changes, decline in school performance.
- Other: hemolysis, renal, osteoarticular, or cardiac involvement, Kayser-Fleischer ring.
Laboratory findings
- Increased free serum copper
- Decreased total serum copper and ceruloplasmin
- Increased 24-hour urinary copper
Physiology:
- ATP7B deficiency, impairing incorporation of copper into ceruloplasmin in the liver
- therefore decreased ceruloplasmin and increased unbound free copper, but decreased total copper due to impaired incorporation
MRI
T2/FLAIR hyperintensities:
Bilateral symmetric involvement of the basal ganglia:
- striatum (caudate nucleus + putamen)
- thalami, globus pallidus
Frontal subcortical white matter
In the posterior fossa:
- midbrain, with sparing of the red nuclei and substantia nigra ("giant panda face" sign)
- middle cerebellar peduncles
- cerebellum
On T1/T2*:
Possible T1 hyperintensity/T2* hypointensity related to copper deposition
Diffusion:
May show restricted diffusion
Management
- Acute phase: chelation with D-penicillamine, trientine
- Maintenance phase (lifelong): reduction of intestinal copper absorption with zinc acetate
Differential diagnosis
Parkinson disease: any parkinsonian syndrome before age 40 should prompt investigation for Wilson disease
Basal ganglia hyperintensities:
- Jakob-creutzfeldt disease
- Anoxic encephalopathy
- Japanese Encephalitis
- methanol intoxication
- Leigh disease
- Huntington chorea
Brainstem hyperintensities:
- central pontine myelinolysis