Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein

Nat Genet. 1995 Feb;9(2):141-5. doi: 10.1038/ng0295-141.


Ataxia with isolated vitamin E deficiency (AVED) is an autosomal recessive neurodegenerative disease which maps to chromosome 8q13. AVED patients have an impaired ability to incorporate alpha-tocopherol into lipoproteins secreted by the liver, a function putatively attributable to the alpha-tocopherol transfer protein (alpha-TTP). Here we report the identification of three frame-shift mutations in the alpha TTP gene. A 744delA mutation accounts for 68% of the mutant alleles in the 17 families analysed and appears to have spread in North Africa and Italy. This mutation correlates with a severe phenotype but alters only the C-terminal tenth of the protein. Two other mutations were found in single families. The finding of alpha TTP gene mutations in AVED patients substantiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Africa, Northern / epidemiology
  • Amino Acid Sequence
  • Ataxia / epidemiology
  • Ataxia / etiology*
  • Ataxia / genetics*
  • Base Sequence
  • Carrier Proteins / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 8*
  • Denmark / epidemiology
  • England / epidemiology
  • Female
  • France / epidemiology
  • Germany / epidemiology
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Pedigree
  • Sicily / epidemiology
  • Vitamin E Deficiency / genetics*


  • Carrier Proteins
  • alpha-tocopherol transfer protein