Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A 22-year-old man presented with progressive gait instability, tremor, and dysarthria since childhood. Electrophysiologic studies revealed a sensorimotor polyneuropathy. Laboratory studies documented vitamin E deficiency; however, no gastrointestinal, hepatic, or lipoprotein disorder could be identified. Vitamin E therapy normalized the serum level, but there was no neurologic improvement. Isolated vitamin E deficiency, in the absence of lipid malabsorption, should be considered in the evaluation of children and adults with ataxia and peripheral neuropathy.
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PMID:Isolated vitamin E deficiency. 876 Dec 74

We describe a patient with a progressive neurological disorder consisting of ataxia, loss of proprioception and pyramidal tract dysfunction in his sixth decade. He had severe vitamin E deficiency due to fat malabsorption secondary to chronic inflammatory bowel disease. Sural nerve biopsy revealed a reduced number of myelinated fibres. MRI of the cervical spine showed high-signal lesions on T2-weighted images in the posterior columns, correlating well with the clinical findings.
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PMID:Spinal MRI in progressive myeloneuropathy associated with vitamin E deficiency. 881 95

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

Friedreich's ataxia is the most common inherited spinocerebellar ataxia. A decade of linkage and physical mapping studies have culminated in the identification of the Friedreich's ataxia gene. The presence of homologues in purple bacterial genomes, but not in other bacteria, allows us to infer a mitochondrial location for frataxin (Friedreich's ataxia protein) on the basis of bacterial phylogeny. Frataxin possesses a non-globular N-terminus domain providing a candidate mitochondrial targeting peptide. Clues to the function of frataxin are provided by the mitochondrial location, a clinically similar ataxia with vitamin E deficiency, and certain neuropathies with mitochondrial DNA instability caused by mutations in nuclear genes.
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PMID:Friedreich's ataxia protein: phylogenetic evidence for mitochondrial dysfunction. 893 Dec 68

We describe 4 siblings of a consanguineous Bedouin family with Friedreich ataxia phenotype in whom low serum vitamin E levels without other indicators of fat malabsorption were detected. Although age of onset and some of the clinical features were alike in all 4 patients, the electrophysiological parameters were markedly abnormal in 2, but normal in the other 2. Erythrocytes revealed both membranous and intracellular evidence of oxidative damage. The mutations described in other families with ataxia with isolated vitamin E deficiency were not detectable, nor was an abnormal single-stranded conformation polymorphism pattern apparent in the three exons at the 3' region of the gene. Vitamin E administration in pharmacological doses improved the neurological condition in 2 patients and also corrected some of the patients' erythrocyte cell abnormalities. The finding of vitamin E deficiency in other cases of Friedreich ataxia phenotype may allow treatment at an early stage of the disease, when large dose Vitamin E therapy may reverse the neurological lesions.
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PMID:Ataxia with isolated vitamin E deficiency in four siblings. 897 36

Vitamin E is one of the most important lipid-soluble antioxidant nutrients. Severe vitamin E deficiency can have a profound effect on the central nervous system. Cystic fibrosis, chronic cholestatic liver disease, abetalipoproteinemia, short bowel syndrome, isolated vitamin E deficiency syndrome and other malabsorption syndromes all may cause varying degrees of neurologic deficits due to related vitamin deficiencies. The classic abnormalities in vitamin E deficiency progress from hyporeflexia, ataxia, limitations in upward gaze and strabismus to long-tract defects, profound muscle weakness and visual field constriction. Patients with severe, prolonged deficiency may develop complete blindness, dementia and cardiac arrhythmias. Treatment must be tailored to the underlying cause of vitamin E deficiency and may include oral or parenteral vitamin supplementation. The more advanced the deficits, the more limited the response to therapy. Therefore, a good neurologic examination and periodic serum vitamin E levels are essential in patients at risk of vitamin E deficiency.
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PMID:Neurologic findings in vitamin E deficiency. 901 78

EDM is a neurologic disease of young horses characterized by the insidious development of symmetric ataxia. Decreased or absent cutaneous trunci reflex or slap test responses are considered clinical signs that increase the index of suspicion for this disease. In addition, concurrent predisposing factors, such as familial history, inadequate access to green pasture, and possible exposure to wood preservatives or insecticides, provide further supporting evidence for a clinical diagnosis. Vitamin E deficiency and a hereditary predisposition currently are considered the most significant factors in the pathogenesis of this disease. Histopathologically the lesions of EDM are those of neuraxonal dystrophy, characterized by prominent axonal and dendritic swelling, mild glial proliferation, and neuronal depletion and atrophy with lipofuscin-like pigment accumulation. Animals predisposed to EDM or with a clinical diagnosis of EDM should receive oral alpha-tocopherol acetate supplementation. Improvement in clinical signs may be seen following long-term treatment, but in general, the prognosis for complete recovery is poor.
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PMID:Equine degenerative myeloencephalopathy. 910 42

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


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