Late-onset Friedreich ataxia: phenotypic analysis, magnetic resonance imaging findings, and review of the literature.
BACKGROUND
Friedreich ataxia (FA), the most common hereditary ataxia, is caused by pathological expansion of GAA repeats in the first intron of the X25 gene on chromosome 9. Since the discovery of the gene, atypical features are increasingly recognized in individuals with FA, and up to 25% of patients with recessive or sporadic ataxia do not fulfill the Harding or Quebec Cooperative Study on Friedreich's Ataxia criteria for FA. Late-onset FA (LOFA) is defined as onset after age 25 years.


OBJECTIVE
To describe and further delineate the clinical and magnetic resonance imaging findings in patients with LOFA and to review the literature.


METHODS
Clinical evaluation and comparison of clinical data and investigations.


METHODS
Ataxia clinics at UCLA and Cedars-Sinai Medical Center.


METHODS
Thirteen patients with LOFA with 13 sex-matched and Inherited Ataxia Progression Scale-matched patients with typical FA.


RESULTS
Gait and limb ataxias were seen in all the participants. Dysarthria, loss of vibration sense, and abnormal eye movements were also common in both groups. Patients with LOFA more often had lower limb spasticity (40% vs 0%; chi2 = 4.0; P = .04) and retained reflexes (46.1% vs 7.7%; chi2 = 3.46; P = .05). They had no complaint of sphincter disturbances, and there was no evidence of cardiomyopathy on echocardiograms (chi2 = 4.0; P = .04). Five of 9 patients with LOFA had cerebellar atrophy on neuroimaging.


CONCLUSIONS
Patients with gait and limb ataxias, dysarthria, loss of vibration sense, and fixational instability after age 25 years should be considered for molecular testing for GAA expansion in the FA gene. In contrast to previous studies, cerebellar vermian atrophy is not an uncommon finding.
Bhidayasiri
Roongroj
R
Department of Neurology, UCLA Medical Center, Los Angeles, Calif, USA. rbh@ucla.edu
Perlman
Susan L
SL
Pulst
Stefan-M
SM
Geschwind
Daniel H
DH
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001284:Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001933:Brain Stem / Q000473:pathology / Q000503:physiopathology; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005621:Friedreich Ataxia / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D020234:Gait Ataxia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009128:Muscle Spasticity / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D012021:Reflex, Abnormal / Q000502:physiology; D012189:Retrospective Studies; D020886:Somatosensory Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*