Friedreich's ataxia after gene cloning genotype-phenotype relationship

Most patients with Friedreich'ataxia (FA) carry a GAA expanded sequence within the first intron of X25 gene. We found both alleles expanded in 100 FA patients from 74 families The expanded alleles ranged from 120 to 1340 repeat units and showed a negatively skewed distribution with a peak between 800 and 1000 repeats. The length of smaller alleles inversely correlated with onset age Mean allele length was significantly higher in patients with diabetes and in those with cardiomyopathy Twenty patients had late onset (21-45 years) and eight patients had retained tendon reflexes Three sibs had late onset, spastic ataxia without peripheral neuropathy Age of onset, lower limb areflexia and even peripheral neuropathy are no more essential diagnostic criteria. Clinical diagnostic criteria for FA appear to be highly specific, but they yield many false negative cases.