A MILD CASE OF FRIEDREICH ATAXIA - LYMPHOCYTE AND SURAL NERVE ANALYSIS FOR GAA REPEAT LENGTH REVEALS SOMATIC MOSAICISM

Friedreich ataxia (FRDA) is an autosomal recessive, neurodegenerative disease, characterized by progressive gait and limb ataxia, dysarthria , lower-limb areflexia, Babinski sign, loss of position and vibration senses, cardiomyopathy, and carbohydrate intolerance. It is the most c ommon inherited ataxia, and is associated with a GAA triplet repeat ex pansion in the first intron of the X25 gene on the long arm of chromos ome 9. We present a case whose clinical diagnosis was initially confou nded by the mildness of the ataxic phenotype and a family history of m ultiple sclerosis. Evaluation of the X25 gene revealed that the patien t was homozygous for the GAA triplet repeat expansion, pathognomonic o f FRDA. Investigation of her sural nerve biopsy revealed a significant ly smaller expansion size, constituting the first direct demonstration of somatic mosaicism involving the nervous system in FRDA. We specula te that a similar contraction in pathologically affected tissues could be the molecular basis for the mildness of the ataxia. (C) 1997 John Wiley & Sons, Inc.