The neuropathology of late-onset Friedreich's ataxia

Cerebellum. 2011 Mar;10(1):96-103. doi: 10.1007/s12311-010-0235-0.

Abstract

Friedreich's ataxia (FRDA) affects very young persons. In a large series, the mean ages of onset and death were 11 and 38 years, respectively. The clinical spectrum of FRDA has expanded after genetic confirmation of the mutation became a routine laboratory test. The main cause of death in juvenile-onset FRDA is cardiomyopathy whereas patients with late-onset are more likely to succumb to neurological disability or an intercurrent illness. Many patients with early onset now survive for 20 years or longer. This study made a systematic comparison of the neuropathology in 14 patients with juvenile onset and long survival, and five patients with late onset and long survival. Mean ages of onset (± standard deviation) were 10 ± 5 and 28 ± 13 years, respectively. Disease durations were 33 ± 11 and 47 ± 11 years, respectively. Cross-sectional areas of the thoracic spinal cord were greatly reduced from the normal state but did not differ between the two groups. Similarly, the neurons of dorsal root ganglia were significantly reduced in size in both juvenile- and late-onset cases of FRDA. The dentate nucleus showed severe loss of neurons as well as modification and destruction of corticonuclear terminals in all FRDA patients. Delayed atrophy of the dentate nucleus is the likely cause of the ataxic phenotype of FRDA in late-onset cases, but the reason for the delay is unknown. Frataxin levels in the dentate nucleus of two patients with late onset were similar to those of seven patients with juvenile onset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Anatomy, Cross-Sectional
  • Cell Size
  • Cerebellar Nuclei / metabolism
  • Cerebellar Nuclei / pathology
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Frataxin
  • Friedreich Ataxia / pathology*
  • Ganglia, Spinal / pathology
  • Humans
  • Immunohistochemistry
  • Iron-Binding Proteins / metabolism
  • Male
  • Middle Aged
  • Nervous System / pathology*
  • Neurons / pathology
  • Spinal Cord / pathology
  • Survival
  • Young Adult

Substances

  • Iron-Binding Proteins