title: Clinical phenotype and neuroimaging findings in a French family with hereditary ferritinopathy (FTL498-499InsTC).
abstract: To describe a family with a hereditary ferritinopathy (HF) due to a mutation in the ferritin light chain gene (FTL498-499InsTC mutation). Case reports of the clinical features, MRI, (18)FDG PET, and pathological findings observed in this family with two patients described in more details. Postural tremor (phenotype-1) or cerebellar signs (phenotype-2) were the first neurological symptoms detected. Parkinsonian, cerebellar and pyramidal syndromes, abnormal involuntary movements, dementia were observed in both phenotypes at more advanced stages. Beside characteristics T2* hypointense signals suggestive of iron accumulation in the striatum, mesencephalon, and cerebellum, we detected more diffuse changes including cerebellar, cortical and subcortical atrophy, cortical iron deposition, and severe leukoencephalopathy. (18)FDG PET showed frontal and cerebellum hypometabolism with more severe frontal defect in patients with cognitive decline. Pathological examination showed ferritin and iron deposition in the liver, kidney, muscle, skin, and in the central nervous system. Members of this family affected by HF due to the FTL498-499InsTC mutation have a specific clinical presentation with initial postural tremor or cerebellar ataxia, followed by pyramidal and extrapyramidal motor syndromes and late severe subcortical dementia.
authors.affiliation: Department of Neurosciences, University Hospital of Toulouse, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Ory-Magne
authors.forename: Christine
authors.initials: C
authors.lastname: Brefel-Courbon
authors.forename: Pierre
authors.initials: P
authors.lastname: Payoux
authors.forename: Sabrina
authors.initials: S
authors.lastname: Debruxelles
authors.forename: Igor
authors.initials: I
authors.lastname: Sibon
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.forename: Pierre
authors.initials: P
authors.lastname: Labauge
authors.forename: Patrice
authors.initials: P
authors.lastname: Menegon
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Uro-Coste
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Marie Bernadetle
authors.initials: MB
authors.lastname: Delisle
authors.forename: Ruben
authors.initials: R
authors.lastname: Vidal
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
mesh_terms: D000328:Adult; D017668:Age of Onset; D001052:Apoferritins / Q000235:genetics*; D001480:Basal Ganglia Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000737:chemistry / Q000473:pathology; D002524:Cerebellar Ataxia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003704:Dementia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005293:Ferritins / Q000032:analysis; D005602:France / Q000453:epidemiology; D006801:Humans; D007501:Iron / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D016254:Mutagenesis, Insertional; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D049268:Positron-Emission Tomography; D012867:Skin / Q000737:chemistry / Q000473:pathology; D014202:Tremor / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C507433:FTL protein, human; D005293:Ferritins; D001052:Apoferritins; D007501:Iron