Relation between trinucleotide GAA repeat length and sensory neuropathy inFriedreich's ataxia

Objective-To verify if GAA expansion size in Friedreich's ataxia could acco unt for the severity of sensory neuropathy. Methods-Retrospective study of 56 patients with Friedreich's ataxia selecte d according to homozygosity for GAA expansion and availability of electroph ysiological findings. Orthodromic sensory conduction velocity in the median nerve was available in all patients and that of the tibial nerve in 46 of them. Data of sural nerve biopsy and of a morphometric analysis were availa ble in 12 of the selected patients. The sensory action potential amplitude at the wrist (wSAP) and at the medial malleolus (m mal SAP) and the percent age of myelinated fibres with diameter larger than 7, 9, and 11 mu m in the sural nerve were correlated with disease duration and GAA expansion size o n the shorter (GAA1) and larger (GAA2) expanded allele in each pair. Pearso n's correlation test and stepwise multiple regression were used for statist ical analysis. Results-A significant inverse correlation between GAA1 size and wSAP, m mal SAP, and percentage of myelinated fibres was found. Stepwise multiple regr ession showed that GAA1 size significantly affects electrophysiological and morphometric data, whereas duration of disease has no effect. Conclusion-The data suggest that the severity of the sensory neuropathy is probably genetically determined and that it is not progressive.