ABSTRACT
The identification of the most common Friedreich’s ataxia (FRDA) mutation, an unstable hyperexpansion of a GAA triplet repeat polymorphism (Campuzano et al., 1996), clarified part of the clinical variation seen among and within families. The cardinal neurological feature of FRDA is a progressive, unremitting mixed cerebellar-sensory ataxia. Most commonly, it begins with clumsiness in gait and frequent falls (truncal ataxia). In the early 1980s, several seemingly contradictory reports suggested that anomalies of the intermediate metabolism were present in FRDA. The FRDA gene was localized on chromosome 9 by linkage analysis with RFLP markers by Chamberlain and colleagues in 1988 and localization was confirmed shortly after with a second RFLP located in 9q13–q21. Cardiomyopathy in FRDA patients could thus be a result of iron overload (as in thalassaemia or in haemochromatosis) or might reflect a selective sensitivity of heart mitochondria to frataxin deficiency.
