Neuroferritinopathy is a progressive potentially treatable adult-onset
movement disorder caused by mutations in the
ferritin light chain gene (FTL1). Features overlap with common
extrapyramidal disorders:
idiopathic torsion dystonia,
idiopathic Parkinson's disease and
Huntington's disease, but the phenotype and natural history have not been defined. We studied a genetically homogeneous group of 41 subjects with the 460InsA mutation in FTL1, documenting the presentation,
clinical course, biochemistry and neuroimaging. The mean age of onset was 39.4 years (SD = 13.3, range 13-63), beginning with
chorea in 50%, focal lower limb
dystonia in 42.5% and
parkinsonism in 7.5%. The majority reported a family history of a
movement disorder often misdiagnosed as
Huntington's disease. The disease progressed relentlessly, becoming generalized over a 5-10 year period, eventually leading to
aphonia,
dysphagia and severe motor disability with subcortical/frontal
cognitive dysfunction as a late feature. A characteristic action-specific facial
dystonia was common (65%), and in 63% there was asymmetry throughout the disease course. Serum
ferritin levels were low in the majority of males and post-menopausal females, but within normal limits for pre-menopausal females. MR brain imaging was abnormal on all affected individuals and one presymptomatic carrier. In conclusion, isolated
parkinsonism is unusual in
neuroferritinopathy, and unlike
Huntington's disease, cognitive changes are absent or subtle in the early stages. Depressed serum
ferritin is common and provides a useful screening test in routine practice, and gradient echo brain MRI will identify all symptomatic cases.