The relationship between trinucleotide GAA repeat lenght and sensory neuropathy in Friedreich Ataxia

The identification of the Friedreich Ataxia (FA) genetic defect has broadened the disease phenotype. Three siblings with minimal expansions and without clinical and electrophysiologic sings of neuropathy have been recently described. To verify the possibility that GAA expansion size accounts for sensory neuropathy severity in FA we studied the relationship between molecular findings and peripheral nerve electrophysiologic findings in 50 patients. Moreover we studied the relationship between the molecular findings and the sural nerve morphometric data in 12 patients. According to the electrophysiologic data an arbitrary score, ranging from 1 to 3, was defined for the neuropathy severity. The neuropathy score, the median nerve sensory action potential at the wrist (wSAP), the mean percentage of myelinated fibers (MF) with diameter larger than 7p.m were correlated with duration of disease and GAA expansion size on the short expanded allele (GAA1). For statistical analysis Spearman's and Pearson's correlation coefficients were calculated. The mean age of patients at the time of the examination and the mean disease duration were respectively 20+/-9 and 6+/-6 years. The wSAP mean value was 1.05+/-0.96 and the mean neuropathy score was 2.8+/-0.5. The mean percentage of MF larger than 7 was 19+/-13. The mean expansion size of GAA1 allele was 732+/-I91. A significant correlation was found between GAA1 and neuropathy score (Spearman's r= 0.33, p<0.05), wSAP (Pearson's r= -0.42, p<0.01), and percentage of largest MF (Pearson's r=-0.872, p< 0.01). No correlation was found between disease duration and any of the considered parameters. These data suggest that the severity of the sensory neuropathy is related to the GAA1 expansion size and confirm that the neuropathy is not progressive.