ORIGINAL

Neurological Sciences

, Volume 25, Issue 3, pp 130-137

Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPAgene in Italian families

  • C. MariottiAffiliated withDivision of Biochemistry and Genetics, C. Besta National Neurological Institute Email author 
  • , C. GelleraAffiliated withDivision of Biochemistry and Genetics, C. Besta National Neurological Institute
  • , M. RimoldiAffiliated withDivision of Biochemistry and Genetics, C. Besta National Neurological Institute
  • , R. MineriAffiliated withDivision of Biochemistry and Genetics, C. Besta National Neurological Institute
  • , G. UzielAffiliated withDepartment of Neuropediatrics, C. Besta National Neurological Institute
  • , G. ZorziAffiliated withDepartment of Neuropediatrics, C. Besta National Neurological Institute
  • , D. PareysonAffiliated withDivision of Biochemistry and Genetics, C. Besta National Neurological Institute
  • , G. PiccoloAffiliated withC. Mondino Neurological Institute, IRCCS
  • , D. GambiAffiliated withCenter for Neuromuscular Diseases, G. D’Annunzio University
    • , S. PiacentiniAffiliated withDepartment of Neurological and Psychiatric Sciences, University of Florence
    • , F. SquitieriAffiliated withNeurogenetics Unit, IRCCS INM Neuromed
    • , R. CapraAffiliated withMultiple Sclerosis Center, Ospedali Civili
    • , B. CastellottiAffiliated withDivision of Biochemistry and Genetics, C. Besta National Neurological Institute
    • , S. Di DonatoAffiliated withDivision of Biochemistry and Genetics, C. Besta National Neurological Institute

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Abstract.

Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disorder due to mutations in the alpha-tocopherol transfer protein (TTPA) gene on chromosome 8q13. AVED patients have progressive spinocerebellar symptoms and markedly reduced plasma levels of vitamin E. We studied neurological phenotype at diagnosis, and long-term effect of vitamin E supplementation in 16 patients from 12 Italian families. The most common mutations were the 744delA and 513insTT. Two novel TTPA mutations were identified: a severe truncating mutation (219insAT) in a homozygous patient, and a Gly246Arg missense mutation (G246R) in a compound heterozygous patient. The missense mutation was associated with a mild and slowly progressive form of the disease. Vitamin E supplementation therapy allowed a stabilization of the neurological conditions in most of the patients. However, development of spasticity and retinitis pigmentosa was noted in a few patients during therapy. Prompt genetic characterization of AVED patients may allow an effective early treatment and an adequate genetic counseling.

Key words

α-Tocopherol transfer protein gene TTPA Recessive ataxia Vitamin E Vitamin E therapy