Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation

Chinnery, PF, Crompton, DE, Birchall, D, Jackson, MJ, Coulthard, A, Lombes, A, Quinn, N, Wills, A, Fletcher, N, Mottershead, JP, Cooper, P, Kellett, M, Bates, D and Burn, J (2007) Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation. Brain, 130 1: 110-119. doi:10.1093/brain/awl319

Author Chinnery, PF
Crompton, DE
Birchall, D
Jackson, MJ
Coulthard, A
Lombes, A
Quinn, N
Wills, A
Fletcher, N
Mottershead, JP
Cooper, P
Kellett, M
Bates, D
Burn, J
Title Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation
Journal name Brain   Check publisher's open access policy
ISSN 0006-8950
Publication date 2007
Sub-type Article (original research)
DOI 10.1093/brain/awl319
Volume 130
Issue 1
Start page 110
End page 119
Total pages 10
Place of publication Oxford
Publisher Oxford Univ Press
Language eng
Abstract 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.
Keyword Clinical Neurology
movement disorder
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: Excellence in Research Australia (ERA) - Collection
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Created: Mon, 18 Feb 2008, 15:58:08 EST