A treatable familial neuromyopathy with vitamin E deficiency, normal absorption, and evidence of increased consumption of vitamin E

Secondary carnitine deficiency and impaired docosahexaenoic (22:6n‐3) acid synthesis: a common denominator in the pathophysiology of diseases of oxidative phosphorylation and β‐oxidation

“…Recent evidence convincingly shows that an impairment of the carnitine synthesis pathway at the step of lysosomal proteolysis of a mitochondrial trimethyllysine‐containing protein is the primary biochemical lesion in this disease [43]. Since NCL patients show both carnitine deficiency and abnormally low levels of 22:6 n ‐3, and higher levels of 20:4 n ‐6 [43–46], an impairment of the carnitine‐dependent pathway of 22:6 n ‐3 synthesis appears to be a major cause of its pathophysiology; this is consistent with data showing that supplementation with 22:6 n ‐3 ameliorates its pathology [47,48]. Other conditions associated with carnitine deficiency, such as treatment with certain pharmacologic agents, vegan diets, and excess dietary fat intake, also show decreased levels of 22:6 n ‐3 (but normal 22:5 n ‐3 levels) and higher levels of 20:4 n ‐6 and 22:5 n ‐6 (when measured) [7,13,49–54].…”

α-Tocopherol as a Reductant for Cu(II) in Human Lipoproteins

“…In separate experiments, LDL was isolated from a 27-year-old male patient with familial isolated vitamin E deficiency (FIVE) (32,33). The patient was homozygotic for a defect in the ␣-tocopherol transfer protein gene (33) and required regular vitamin E supplements (1800 mg daily).…”

Ataxia with Isolated Vitamin E Deficiency: Heterogeneity of Mutations and Phenotypic Variability in a Large Number of Families

“…Families 3 and 4 (referred by M. Ben Hamida) and 9 and 17 (referred by A. Benomar) belong to large series of Tunisian and Moroccan families, respectively, and are not part of this study. Clinical descriptions were reported elsewhere for families 13 (Burck et al 1981;Kohlschü tter et al 1988), 18 (Laplante et al 1984), 14 (Sokol et al 1988), 16 (Trabert et al 1989), 1 and 2 (Ben Hamida et al 1993b), 8 (Amiel et al 1995, and 28 (Martinello et al, in press), and mutation was reported for 10 families (Ouahchi et al 1995). In addition to the 27 families analyzed here, molecular and clinical data from 6 families were compiled from the literature (Gotoda et al 1995;Hentati et al 1996;Yokota et al 1996Yokota et al , 1997.…”

“…Our experience has shown that, in AVED patients, there is no limitation to or difficulty with the absorption of vitamin E by the intestinal tract (Kayden and Traber 1993). The administration of vitamin E supplements in divided doses daily has resulted in cessation of progression of the neurological symptoms and signs and in amelioration of established neurological abnormalities, in a number of patients (Kohlschü tter et al 1988;Yokota et al 1997). Our experience is that, for adults, the administration of 800 mg RRR a-tocopherol twice daily, with meals that contain fat, results in plasma a-tocopherol Table 5 Correlation between Genotype and Discrimination among Stereoisomers of a-Tocopherol a "Hentati" indicates a family from the study by Hentati et al (1996); "Gotoda" indicates a family from the study by Gotoda et al (1995); Numbering is according to Traber et al (1993).…”

“…In normal individuals, the latter function accounts for the efficient recycling of plasma vitamin E ( pools/d) that otherwise is 1.4 ‫ע‬ 0.6 rapidly eliminated (Traber et al 1994). FIVE has been described in rare cases, studied during the period 1981-89 (Burck et al 1981;Laplante et al 1984;Harding et al 1985;Krendel et al 1987;Stumpf et al 1987;Yokota et al 1987;Kohlschü tter et al 1988;Sokol et al 1988;Trabert et al 1989). The description, reported in 1993, of eight affected individuals from two large Tunisian pedigrees (Ben Hamida et al 1993b) initiated the identification of many other patients from North Africa, where this condition appears to be much more frequent.…”