Clinical phenotype and neuroimaging findings in a French family with hereditary ferritinopathy (FTL498-499InsTC)

Mov Disord. 2009 Aug 15;24(11):1676-83. doi: 10.1002/mds.22669.

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age of Onset
  • Apoferritins / genetics*
  • Basal Ganglia Diseases / diagnostic imaging
  • Basal Ganglia Diseases / genetics*
  • Basal Ganglia Diseases / metabolism
  • Basal Ganglia Diseases / pathology
  • Central Nervous System / chemistry
  • Central Nervous System / pathology
  • Cerebellar Ataxia / diagnostic imaging
  • Cerebellar Ataxia / genetics*
  • Cerebellar Ataxia / metabolism
  • Cerebellar Ataxia / pathology
  • Dementia / diagnostic imaging
  • Dementia / genetics*
  • Dementia / metabolism
  • Dementia / pathology
  • Female
  • Ferritins / analysis
  • France / epidemiology
  • Humans
  • Iron / analysis
  • Liver / chemistry
  • Liver / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Movement Disorders / diagnostic imaging
  • Movement Disorders / genetics*
  • Movement Disorders / metabolism
  • Movement Disorders / pathology
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / pathology
  • Mutagenesis, Insertional
  • Mutation
  • Pedigree
  • Phenotype
  • Positron-Emission Tomography
  • Skin / chemistry
  • Skin / pathology
  • Tremor / diagnostic imaging
  • Tremor / genetics
  • Tremor / metabolism
  • Tremor / pathology

Substances

  • FTL protein, human
  • Ferritins
  • Apoferritins
  • Iron