ATAXIA WITH ISOLATED VITAMIN-E-DEFICIENCY - HETEROGENEITY OF MUTATIONS AND PHENOTYPIC VARIABILITY IN A LARGE NUMBER OF FAMILIES

Ataxia with vitamin E deficiency (AVED), or familial isolated vitamin E deficiency, is a rare autosomal recessive neurodegenerative disease characterized clinically by symptoms with often striking resemblance t o those of Friedreich ataxia. We recently have demonstrated that AVED is caused by mutations in the gene for alpha-tocopherol transfer prote in (alpha-TTP). We now have identified a total of 13 mutations in 27 f amilies. Four mutations were found in greater than or equal to 2 indep endent families: 714delA, which is the major mutation in North Africa, and 513insTT 486delT, and R134X, in families of European origin. Comp ilation of the clinical records of 43 patients with documented mutatio n in the alpha-TTP gene revealed differences from Friedreich ataxia: c ardiomyopathy was found in only 19% of cases, whereas head titubation was found in 28% of cases and dystonia in an additional 13%. This stud y represents the largest group of patients and mutations reported for this often misdiagnosed disease and points to the need for an early di fferential diagnosis with Friedreich ataxia, in order to initiate ther apeutic and prophylactic vitamin E supplementation before irreversible damage develops.