Neuroferritinopathy: update on clinical features and pathogenesis

Abstract

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.