Ataxia with vitamin E deficiency: update of molecular diagnosis.
Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disease, due to mutations in TTPA gene (Arita et al. in Biochem J 306(Pt. 2):437-443, 1995; Hentati et al. in Ann Neurol 39:295-300, 1996), which encodes for alpha-TTP, a cytosolic liver protein that is presumed to function in the intracellular transport of alpha-tocopherol. This disease is characterized clinically by symptoms with often striking resemblance to those of Friedreich ataxia. The neurological symptoms include ataxia, dysarthria, hyporeflexia, and decreased vibration sense, sometimes associated with cardiomyopathy and retinitis pigmentosa (Mariotti et al. in Neurol Sci 25:130-137, 2004). Vitamin E supplementation improves symptoms and prevents disease progress (Doria-Lamba et al. in Eur J Pediatr 165(7):494-495, 2006). Over 20 mutations have been identified in patients with AVED. In the present paper we summarize the recent findings on molecular genetic of this disease including the list of the known mutations.
Di Donato
I
I
Dipartimento di Scienze Neurologiche, Neurochirurgiche e del Comportamento, Università degli Studi di Siena, Viale Bracci, 53100, Siena, Italy.
Bianchi
S
S
Federico
A
A
D000975:Antioxidants / Q000627:therapeutic use; D001259:Ataxia / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D008967:Molecular Biology; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000209:etiology / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000235:genetics; D014810:Vitamin E / Q000627:therapeutic use; D014811:Vitamin E Deficiency / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*
D000975:Antioxidants; D014810:Vitamin E; D010959:Tissue Plasminogen Activator
N Engl J Med. 1996 Dec 5;335(23):1770-1
8965888
Neurology. 1997 Aug;49(2):584-8
9270601
Vitam Horm. 2007;76:23-43
17628170
Turk J Pediatr. 2008 Sep-Oct;50(5):471-5
19102053
Ann Neurol. 1999 Jun;45(6):809-12
10360777
Ann Neurol. 1997 Jun;41(6):826-32
9189046
Adv Pharmacol. 1997;38:49-63
8895803
Eur J Pediatr. 2006 Jul;165(7):494-5
16491382
J Neurol Neurosurg Psychiatry. 2000 Aug;69(2):254-6
10896705
Neurol Sci. 2004 Jul;25(3):130-7
15300460
Neurology. 2000 Nov 28;55(10):1584-6
11094124
Orphanet J Rare Dis. 2006 Nov 17;1:47
17112370
Eur J Med Genet. 2005 Jan-Mar;48(1):21-8
15953402
Mov Disord. 2002 May;17(3):612-4
12112220
Ann Neurol. 1996 Mar;39(3):295-300
8602747
Acta Neurol Scand Suppl. 2009;(189):42-5
19566498
Biochemistry. 2006 Jan 31;45(4):1075-81
16430203
Vitam Horm. 2007;76:45-65
17628171
Pediatr Res. 2008 Sep;64(3):262-4
18458655
Lancet Neurol. 2007 Mar;6(3):245-57
17303531
Ann Neurol. 1987 Jul;22(1):84-7
3477125
Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14713-8
14657365
Pathol Biol (Paris). 2009 Jul;57(5):425-6
19038506
Mol Aspects Med. 2007 Oct-Dec;28(5-6):400-22
17624418
J Lab Clin Med. 1988 May;111(5):548-59
3361234
Nat Genet. 1993 Oct;5(2):195-200
8252047
J Pediatr Gastroenterol Nutr. 2001 Aug;33(2):206-10
11568526
N Engl J Med. 1995 Nov 16;333(20):1313-8
7566022
J Pediatr. 1999 Feb;134(2):240-4
9931538
Jpn J Ophthalmol. 2001 Nov-Dec;45(6):672-6
11754917
Arch Neurol. 2002 Dec;59(12):1952-3
12470185
Biochemistry. 2006 Jul 11;45(27):8236-42
16819822
Mol Aspects Med. 2007 Oct-Dec;28(5-6):591-606
17306357
Eur J Neurol. 2001 Sep;8(5):477-81
11554913
Curr Opin Neurobiol. 1997 Oct;7(5):689-94
9384553
Ann Neurol. 1998 Feb;43(2):273
9485073
Parkinsonism Relat Disord. 2007 Jul;13(5):315-6
17049453
Am J Clin Nutr. 1998 Aug;68(2):311-8
9701188
Neurogenetics. 2010 Feb;11(1):1-12
19440741
Neurol Sci. 2001 Jun;22(3):219-28
11731874
J Neurol Neurosurg Psychiatry. 2000 Apr;68(4):521-5
10727494
J Biol Chem. 1993 Aug 25;268(24):17705-10
8349655
Nat Clin Pract Neurol. 2008 Jul;4(7):E1; author reply E2
18600251
J Neurol Sci. 1998 Apr 1;156(2):177-9
9588854
Nat Genet. 1995 Feb;9(2):141-5
7719340
Eur J Pediatr. 2006 Jul;165(7):429-34
16491383
Biochem J. 1995 Mar 1;306 ( Pt 2):437-43
7887897
J Neurogenet. 2008;22(2):139-48
18569450
Neuropediatrics. 1981 Aug;12(3):267-78
6945489
Am J Hum Genet. 1998 Feb;62(2):301-10
9463307
J Neurol Sci. 2002 Jun 15;198(1-2):25-9
12039660
Brain Dev. 2003 Sep;25(6):442-5
12907280