Mitochondrial DNA haplogroups influence the Friedreich's ataxia phenotype

3 Diabetes mellitus or carbohydrate intolerance is frequently described. 1 The age of onset is variable. The disease usually comes at puberty but several cases have become symptomatic after 40 years. 4 The mole- cular defect that occurs in Friedreich's ataxia is the trinucleotide GAA expansion in the first intron of the X25 gene. This gene encodes for a 210 aa mitochondrial protein called frataxin. 5 Levels of frataxin mRNA and protein are severely reduced as a result of this expansion. 5 Although the exact physiological function of frataxin is not known, its involvement in iron-sulphur (Fe-S) cluster biogenesis 6 has been suggested. The Friedreich's ataxia phenotype shows a variable expression with respect to the age of onset and the presence of some signs or symptoms. Disease duration has been proposed to influence dysarthria, decreased vibration sense, optic atrophy, and diabetes. 7 Some Friedreich's ataxia phenotype features are strongly correlated with GAA expan- sion size. An inverse relationship has been demonstrated between GAA repeat size and the age of onset. 78 Friedreich's ataxia with retained reflexes or absence of cardiomyopathy was associated with shorter expansions. In a previous report, we demonstrated that GAA size accounts for about 70% of the onset age variance, 8