Document Detail

Friedreich ataxia: neuropathology revised.
MedLine Citation:
PMID:  23334592     Owner:  NLM     Status:  MEDLINE    
Friedreich ataxia is an autosomal recessive disorder that affects children and young adults. The mutation consists of a homozygous guanine-adenine-adenine trinucleotide repeat expansion that causes deficiency of frataxin, a small nuclear genome-encoded mitochondrial protein. Low frataxin levels lead to insufficient biosynthesis of iron-sulfur clusters that are required for mitochondrial electron transport and assembly of functional aconitase, and iron dysmetabolism of the entire cell. This review of the neuropathology of Friedreich ataxia stresses the critical role of hypoplasia and superimposed atrophy of dorsal root ganglia. Progressive destruction of dorsal root ganglia accounts for thinning of dorsal roots, degeneration of dorsal columns, transsynaptic atrophy of nerve cells in Clarke column and dorsal spinocerebellar fibers, atrophy of gracile and cuneate nuclei, and neuropathy of sensory nerves. The lesion of the dentate nucleus consists of progressive and selective atrophy of large glutamatergic neurons and grumose degeneration of corticonuclear synaptic terminals that contain γ-aminobutyric acid (GABA). Small GABA-ergic neurons and their projection fibers in the dentato-olivary tract survive. Atrophy of Betz cells and corticospinal tracts constitute a second intrinsic CNS lesion. In light of the selective vulnerability of organs and tissues to systemic frataxin deficiency, many questions about the pathogenesis of Friedreich ataxia remain.
Arnulf H Koeppen; Joseph E Mazurkiewicz
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  72     ISSN:  1554-6578     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-03-11     Revised Date:  2013-11-07    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  78-90     Citation Subset:  IM    
Research Service, Veterans Affairs Medical Center, Albany, New York 12208, USA.
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MeSH Terms
Atrophy / etiology,  pathology
Cerebellar Nuclei / pathology
Friedreich Ataxia / genetics,  pathology*
GABAergic Neurons / pathology
Ganglia, Spinal / pathology*
Iron-Binding Proteins / genetics,  metabolism
Pyramidal Tracts / pathology*
Trinucleotide Repeat Expansion / genetics
Grant Support
Reg. No./Substance:
0/Iron-Binding Proteins; 0/frataxin

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