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

• Published in: Neurological sciences 2004-07, Vol.25 (3), p.130-137
• Main Authors: Mariotti, C, Gellera, C, Rimoldi, M, Mineri, R, Uziel, G, Zorzi, G, Pareyson, D, Piccolo, G, Gambi, D, Piacentini, S, Squitieri, F, Capra, R, Castellotti, B, Di Donato, S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Ataxia - diagnosis; Ataxia - genetics; Ataxia - therapy; Carrier Proteins - genetics; Female; Follow-Up Studies; Humans; Italy; Male; Middle Aged; Mutation; Nervous System Diseases - diagnosis; Nervous System Diseases - genetics; Nervous System Diseases - therapy; Pedigree; Phenotype; Vitamin E - therapeutic use; Vitamin E Deficiency - diagnosis; Vitamin E Deficiency - genetics; Vitamin E Deficiency - therapy
• ISSN: 1590-1874
• DOI: 10.1007/s10072-004-0246-z

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.