Clinical phenotype and neuroimaging findings in a French family with hereditary ferritinopathy (FTL498-499InsTC).
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.
Ory-Magne
Fabienne
F
Department of Neurosciences, University Hospital of Toulouse, France.
Brefel-Courbon
Christine
C
Payoux
Pierre
P
Debruxelles
Sabrina
S
Sibon
Igor
I
Goizet
Cyril
C
Labauge
Pierre
P
Menegon
Patrice
P
Uro-Coste
Emmanuelle
E
Ghetti
Bernardino
B
Delisle
Marie Bernadetle
MB
Vidal
Ruben
R
Rascol
Olivier
O
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
C507433:FTL protein, human; D005293:Ferritins; D001052:Apoferritins; D007501:Iron