Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042875 (vitamin E deficiency)
 916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major neurological deterioration, beginning with ataxia, led to the diagnosis of familial vitamin E deficiency in a girl. Based upon vitamin E determinations, 4/8 members of the (consanguineous) sibship were considered to be homozygous. Homozygosity was also found for the alleles of six markers linked to the AVED locus, recently identified in similar Tunisian or Sicilian families on chromosome 8q. Measures of vitamin E in lipoprotein fractions and in liver biopsy after vitamin E oral load suggested that free diffusion of vitamin E between the different compartments was possible and even increased. However, a high-affinity ligand seemed to be lacking, either in the hepatic recycling of vitamin E or in both the hepatic and the other vitamin E compartments. The 5-year substitutive treatment was successful only in the pre- or paucisymptomatic patients. Serum vitamin E must be measured in any unexplained progressive ataxia.
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PMID:Familial isolated vitamin E deficiency. Extensive study of a large family with a 5-year therapeutic follow-up. 747 1

Ataxia with isolated vitamin E deficiency (AVED) is an autosomal recessive neurodegenerative disease which maps to chromosome 8q13. AVED patients have an impaired ability to incorporate alpha-tocopherol into lipoproteins secreted by the liver, a function putatively attributable to the alpha-tocopherol transfer protein (alpha-TTP). Here we report the identification of three frame-shift mutations in the alpha TTP gene. A 744delA mutation accounts for 68% of the mutant alleles in the 17 families analysed and appears to have spread in North Africa and Italy. This mutation correlates with a severe phenotype but alters only the C-terminal tenth of the protein. Two other mutations were found in single families. The finding of alpha TTP gene mutations in AVED patients substantiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.
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PMID:Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein. 771 40

Familial vitamin E deficiency (AVED) causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. AVED is thought to be caused by a defect in the transport of vitamin E in liver cells, which is the probable function of alpha-tocopherol transfer protein (alphaTTP). We have cloned the cDNA and several genomic phage clones covering the entire human alphaTTP gene and determined the junctions between the five exons and four introns that composed the gene for human alphaTTP. Three mutations in three unrelated North American families with AVED were identified. Two mutations, 485delT and 513insTT, cause a frame shift and a premature stop codon and the third mutation 574G-->A would substitute Arg192 to His in alphaTTP. The 2 patients with a severe form of AVED were homozygous with 485delT and 513insTT, respectively, while the patient with a mild form of the disease was compound heterozygous with 513insTT and 574G-->A. These findings have identified the underlying genetic defect in AVED and have confirmed the role of alphaTTP in AVED.
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PMID:Human alpha-tocopherol transfer protein: gene structure and mutations in familial vitamin E deficiency. 860 47

How much vitamin E is enough? An established use of supplemental vitamin E in humans is in the prevention and therapy of deficiency symptoms. The cause of vitamin E deficiency, characterized by peripheral neuropathy and ataxia, is usually malabsorption-a result of fat malabsorption or genetic abnormalities in lipoprotein metabolism. Genetic abnormalities in the hepatic alpha-tocopherol transfer protein also cause vitamin E deficiency-defects in this protein cause an impairment in plasma vitamin E transport. Impaired delivery of vitamin E to tissues, thereby, results in deficiency symptoms. Also discussed is the use of supplemental vitamin E in chronic diseases such as ischemic heart disease, atherosclerosis, diabetes, cataracts, Parkinson's disease, Alzheimer's disease, and impared immune function, as well as in subjects receiving total parenterol nutrition. In healthy individuals, a daily intake of about 15-30 mg of alpha-tocopherol is recommended to obtain "optimal plasma alpha-tocopherol concentrations" (30 microM or greater).
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PMID:Vitamin E in humans: demand and delivery. 883 30

Using a subtraction-enhanced display technique, we identified a rodent alpha-tocopherol transfer protein (alpha-TTP) cDNA which exhibited markedly lower messenger RNA (mRNA) amounts in rat hepatocellular carcinoma (HCC) than in healthy controls. Several lines of evidence have substantiated that abnormal alpha-TTP results in isolated vitamin E deficiency. In this study, we investigated the hepatic mRNA amounts of alpha-TTP during rat hepatic carcinogenesis and liver regeneration on Northern blot, localization of alpha-TTP mRNA in HCC of rats and humans by in situ hybridization, and we analyzed the correlation between alpha-TTP mRNA and alpha-tocopherol. alpha-TTP mRNA concentrations of the rats were decreased at the early stage of hepatic carcinogenesis, and remained 3-5-fold reduced as the tumor progressed. In parallel, serum alpha-tocopherol concentrations were significantly decreased to 40% of those in the controls at the early stages of rat hepatic carcinogenesis (p < 0.01). The 2 data sets were strongly correlated (r = 0.834, p < 0.001). In situ hybridization revealed that a decrease of alpha-TTP mRNA was preferentially localized in the tumor nodules of rats and humans with HCC. Our data suggest that repressed transcription of alpha-TTP is associated with a decrease of serum alpha-tocopherol and with hepatic carcinogenesis.
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PMID:Correlation of repressed transcription of alpha-tocopherol transfer protein with serum alpha-tocopherol during hepatocarcinogenesis. 917 27

The alpha-tocopherol transfer protein (alpha-TTP) is a cytosolic liver protein that is presumed to function in the intracellular transport of alpha-tocopherol, the most biologically active form of vitamin E. We studied 4 unrelated patients with autosomal recessive Friedreich-like ataxia who had isolated vitamin E deficiency. A point mutation was identified in all of them at position 101 of the gene for alpha-TTP, where histidine (CAT) was replaced with glutamine (CAG). Three of the 4 patients developed retinitis pigmentosa subsequent to the onset of ataxia. Neurological symptoms included ataxia, dysarthria, hyporeflexia, and decreased proprioceptive and vibratory sensations. Electrophysiological and pathological examinations showed that the cardinal sites affected were the central axons of dorsal root ganglion cells and the retina, with minor involvement of the peripheral sensory nerve, optic nerve, and pyramidal tract. The vitamin E tolerance test performed showed that the absorption of vitamin E was normal but that its decrease from the serum was accelerated. Oral administration of vitamin E appeared to halt the progression of visual and neurological symptoms. We propose a new treatable syndrome of Friedreich-like ataxia and retinitis pigmentosa caused by a defect in the alpha-TTP gene.
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PMID:Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the alpha-tocopherol transfer protein gene. 948 73

This report concerns the characterization of the alpha-tocopherol transfer protein (alpha-TTP) gene in a Japanese family affected by ataxia with isolated vitamin E deficiency (AVED). The sequence analysis revealed a G-to-A transition at the 3' end of exon 3 in both alleles, which predicts outsplicing of this exon from premessenger RNA and the concomitant frame shift in the ataxic patient. We used reverse transcriptase-polymerase chain reaction to analyze alpha-TTP gene transcripts. All transcripts in peripheral blood lymphocytes of the AVED patient, who was treated with large doses of vitamin E, lacked exon 3. The deduced truncated protein shares only 43% of the normal alpha-TTP. Normal control tissues and cells contained normal transcripts and, unexpectedly, also the same mutant transcripts as those of the patient, although with different transcription levels. Treatment of normal fibroblasts with clinically relevant concentrations of vitamin E increased production of transcripts in a dose-dependent manner. We propose that exon skipping of all transcripts through the complete inactivation of the splice site accounts for the clinical onset of AVED and for the clinical resistance to vitamin E in our patient.
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PMID:alpha-Tocopherol transfer protein gene: exon skipping of all transcripts causes ataxia. 927 Jun 1

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 alpha-tocopherol transfer protein (alpha-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 alpha-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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PMID:Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. 946 7

A 24-year-old patient, born from consanguineous parents, consulted for cerebellar syndrome, ataxia, loss of proprioception, bilateral Babinski sign and lower limbs areflexia. No mutation on Friedreich's ataxia gene was found. Plasmatic vitamin E level was extremely low. Point mutation on gene coding for alpha-tocopherol transfer protein (alpha-TTP) confirmed the diagnosis of familial isolated vitamin E deficiency (AVED). Vitamin E therapy restored normal serum levels and neurological symptoms were stabilized.
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PMID:[Friedreich's ataxia and hereditary vitamin E deficiency. Case study]. 977 63

To study how the expression of alpha-tocopherol transfer protein (alpha-TTP) and its mRNA are affected by protein and vitamin E status, Long-Evans male weanling rats were fed a vitamin E-deficient (DE), high vitamin E (HE, 5 g/kg diet of all-rac-alpha-tocopheryl acetate) or control (C) diet for 12 wk in Experiment 1; and fed a low-protein (LP) or control (C) diet for 6 wk in Experiment 2. The high and deficient vitamin E status of HE and DE groups in Experiment 1 were confirmed by changes in plasma pyruvate kinase activity as well as the concentrations of alpha-tocopherol in plasma and liver. As shown by the Northern and Western Blot Analysis, the expression of alpha-TTP in the liver of the DE group was significantly lower than, while that of the HE group was not different from, that of the controls. In contrast, the alpha-TTP mRNA levels did not differ among the C, DE and HE groups. alpha-Tocopherol in most peripheral tissues of rats fed the LP diet in Experiment 2 was significantly lower than that of the C. Both the alpha-TTP and its mRNA were significantly lower in the LP group than in the C. The results suggested that dietary vitamin E does not affect alpha-TTP gene expression except that the protein levels in the liver were lowered by vitamin E deficiency. On the other hand, protein inadequacy appeared to down-regulate the expression of the alpha-TTP gene.
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PMID:Liver alpha-tocopherol transfer protein and its mRNA are differentially altered by dietary vitamin E deficiency and protein insufficiency in rats. 986 80


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