A novel delins mutation in the alpha-TTP gene in a family segregating ataxia with isolated vitamin E deficiency

Abstract

Ataxia with isolated vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disease due to mutations in the alpha-TTP (alpha-tocopherol transfer protein) gene. In AVED, the biochemical hallmark is the low plasmatic levels of vitamin E and in most of patients, vitamin E supplementation allows a stabilization of the neurological conditions. We have investigated the genetic cause of ataxia and reduced levels of vitamin E, and apolipoproteins A1 (apoA1) and B (apoB) in a 16-year-old patient. Results revealed that our propositus is a compound heterozygote for the c.227_229delinsATT/c.744delA mutations in the -TTP gene, each inherited from one of the two parents. His sister is also a compound heterozygote for both mutations and she presents a biochemical pattern similar to that of his brother. After receiving the vitamin E supplementation, plasmatic levels of vitamin E and apoA1 have been normalized in the propositus. The detected mutations would justify the undetectable levels of vitamin E, but would not explain the also decreased levels of the apolipoproteins, as neither that after treatment with vitamin E, the levels of apoB do not become normal. These findings suggest that other genes may play a role in producing this atypical biochemical profile.