Copyright © 1998 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 62, Issue 2, 301-310, 1 February 1998
doi:10.1086/301699
Ataxia with Isolated Vitamin E Deficiency: Heterogeneity of Mutations and Phenotypic Variability in a Large Number of Families
Laurent Cavalier1, 2, Karim Ouahchi∗, 1, Herbert J. Kayden3, Stephano Di Donato4, Laurence Reutenauer1, Jean-Louis Mandel1, 2, 
, 
and Michel Koenig1, 2
1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut Nationale de la Santé et de la Recherche Médicale/Université Louis Pasteur
2 Faculté de Médecine, Hôpitaux Universitaires de Strasbourg, Strasbourg
3 Department of Medicine, New York University Medical Center, New York
4 Dipartimento di Biochimica e Genetica, Istituto Nazionale Neurologico 'Carlo Besta', Milan
Address for correspondence and reprints: Dr. Michel Koenig, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries BP163, 67404 Illkirch cedex, Strasbourg, France∗ Present affiliation: Northwestern Institute for Neurosciences, Chicago.
Abstract
Ataxia with vitamin E deficiency (AVED), or familial isolated vitamin E deficiency, is a rare autosomal recessive neurodegenerative disease characterized clinically by symptoms with often striking resemblance to those of Friedreich ataxia. We recently have demonstrated that AVED is caused by mutations in the gene for α-tocopherol transfer protein (α-TTP). We now have identified a total of 13 mutations in 27 families. Four mutations were found in ⩾2 independent families: 744delA, which is the major mutation in North Africa, and 513insTT, 486delT, and R134X, in families of European origin. Compilation of the clinical records of 43 patients with documented mutation in the α-TTP gene revealed differences from Friedreich ataxia: cardiomyopathy was found in only 19% of cases, whereas head titubation was found in 28% of cases and dystonia in an additional 13%. This study represents the largest group of patients and mutations reported for this often misdiagnosed disease and points to the need for an early differential diagnosis with Friedreich ataxia, in order to initiate therapeutic and prophylactic vitamin E supplementation before irreversible damage develops.
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