Neuroferritinopathy: Update on Clinical Features and Pathogenesis
Patrick F. Chinnery.
Neuroferritinopathy is an autosomal dominant extra – pyramidal movement disorder caused by mutations in the
ferritin light chain gene (FTL). The most frequent presentation is with chorea (50%), followed by dystonia (42.5 %) and
parkinsonism (7.5%). Seven different mutations are known; 6 insertions in exon 4 and a missense mutation in exon 3 with
the 460insA mutation in exon 4 being the most common. Brain magnetic resonance imaging demonstrates iron deposition
in the basal ganglia and cavitation. Neuropathological studies have shown neuronal loss in the cerebral cortex, cerebellum
and basal ganglia. Ferritin inclusion bodies were demonstrated within neurons and glia. Studies of patient derived fibroblasts
and HeLa cells expressing mutant ferritin demonstrate increased iron levels and oxidative stress. These abnormalities
have been recapitulated in mouse models of neuroferritinopathy. There is no disease modifying treatement for neuroferritinopathy
but benzodiazepines and botulinum toxin may palliate dystonia and tetrabenazine may relieve chorea and
facial tics. There is no role for iron chelation.
Keywords: Ferritin light chain, magnetic resonance imaging, neuroferritinopathy, chorea, dystonia, parkinsonism, benzodiazepines, botulinum toxin, tetrabenazine
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