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 common inherited ataxia, and is associated with a GAA triplet repeat expansion in the first intron of the X25 gene on the long arm of chromosome 9. We present a case whose clinical diagnosis was initially confounded by the mildness of the ataxic phenotype and a family history of multiple sclerosis. Evaluation of the X25 gene revealed that the patient was homozygous for the GAA triplet repeat expansion, pathognomonic of FRDA. Investigation of her sural nerve biopsy revealed a significantly smaller expansion size, constituting the first direct demonstration of somatic mosaicism involving the nervous system in FRDA. We speculate that a similar contraction in pathologically affected tissues could be the molecular basis for the mildness of the ataxia.