Ataxia with isolated vitamin E deficiency

Federico, A., Ataxia with isolated vitamin E deficiency a treatable neurologic disorder resembling Friedreich s ataxia, Neurol. Sci. 25 (3), 119-121, 2004. 

Liver secretion of very low density lipoproteins contributed to the daily turnover of plasma RRR-a-tocopherol. Patients with the autosomal recessive neurodegenerative disease called ataxia with isolated vitamin E deficiency have an impaired ability to incorporate a-tocopherol into very low density lipoproteins secreted by the liver, because of mutations in the gene encoding the tocopherol transfer protein. 

Ouahchi K, Arita M, Kayden H, Hentati F, Ben Hamida M, Sokol R, Aral H, Inoue K, Mandel JL, and Koenig M (1995) Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein. Nature Genetics 9 141-145. 

The hepatic 31 kDa a-TTP is a cytosolic protein that has been purified and found to exist as two charge isoforms (Kuhlenkamp et al, 1993). The primary structures of a-TTP from rat liver (Sato et al, 1993) and human liver (Arita et al, 1995) have been determined and found to have a structural homology with retinaldehyde-binding protein (Sato et al, 1993). It is now known that a defect in a-TTP is the cause of ataxia (a nervous disorder characterized by the inability to coordinate muscular movement) associated with familial isolated vitamin E deficiency (Traber etal, 1990c Schuelke etal, 1999). Recent work also indicates that a-TTP is very important for the normal development of placental labyrinthine trophoblasts the placenta of female mice deficient in a-TTP was found to be extremely impaired and the embryos died at mid-gestation (Jishage et al, 2001). 

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