Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families.
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.
Mariotti
C
C
Division of Biochemistry and Genetics, C. Besta National Neurological Institute, Via Celoria 11, I-20133 Milan, Italy. mariotti@istituto-besta.it
Gellera
C
C
Rimoldi
M
M
Mineri
R
R
Uziel
G
G
Zorzi
G
G
Pareyson
D
D
Piccolo
G
G
Gambi
D
D
Piacentini
S
S
Squitieri
F
F
Capra
R
R
Castellotti
B
B
Di Donato
S
S
D000293:Adolescent; D000328:Adult; D001259:Ataxia / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009422:Nervous System Diseases / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D010375:Pedigree; D010641:Phenotype; D014810:Vitamin E / Q000627:therapeutic use; D014811:Vitamin E Deficiency / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy
D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein; D014810:Vitamin E