Classical Friedreich's ataxia and its genotype

Fourteen patients with classical features of Friedreich's ataxia (FRDA) wer e examined. The clinical diagnosis of FRDA was afterwards confirmed in all patients by the appropriate DNA investigation which showed markedly increas ed amounts of GAA repeats on both alleles of the frataxin gene. None of our patients presented with atypi- cal features such as late-onset FRDA, FRDA with retained deep tendon reflexes or with a very slow course. Five of them are not yet confined to a wheelchair. But for 1 patient who died at age 36 years and had the largest number of GAA repeats on both alleles, there was no significant correlation between number of repeats in the shortest allel e, age at onset, age at wheelchair dependence, duration of the disease and main clinical signs. All patients but 3 had between 500 and 1,050 GAA repea ts. The 3 patients with, respectively, 400, 450 and 500 repeats on the shor test allele had a clinical course comparable to the other patients. Even in the case of variations in the number of repeats in the same sibship, there were only modest differences between the siblings concerning age at onset of the disease, symptoms and signs and age at wheelchair dependence. There were no qualitative differences in the main clinical features and laborator y investigations in the full-blown phase of the disorder. Molecular biology has become a major element in the diagnosis of FRDA. DNA testing for FRDA should be applied to every case of idiopathic autosomal recessive or sporad ic ataxia. However, the clinical features of FRDA remain fully characterist ic in many patients and keep their diagnostic value.