Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 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.
 ...
PMID:Human alpha-tocopherol transfer protein: gene structure and mutations in familial vitamin E deficiency. 860 47

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.
 ...
PMID:[Friedreich's ataxia and hereditary vitamin E deficiency. Case study]. 977 63

Spinocerebellar ataxias comprise a poorly understood group of inherited degenerative neurological diseases. Attempts to classify hereditary ataxias on the basis of the neurological features or specific clinical signs such as tendon reflex changes have proven to be unsatisfactory. Early onset cerebellar ataxia (EOCA) is generally inherited as an autosomal-recessive trait. Thus far, we do not have accurate answers to several questions about its classification. However, significant clinical heterogeneity observed in four Tunisian families with typical EOCA clinical features reinforces the hypothesis of genetic heterogeneity underlying this phenotype. We have demonstrated that three of the four families studied were not linked to Friedreich's ataxia (FA), vitamin E deficiency ataxia (AVED), and autosomal dominant cerebellar ataxia (ADCA) loci. The fourth family showed homozygosity for a large pathological expansion of GAA repeat in all patients, the parents being heterozygous for this mutation. We have also noted, in the case of the family studied, that there was instability in the transmission of the mutation, along with a phenomenon of anticipation comparable to that observed in dominant triplet repeat diseases. EOCA is thus clinically indistinguishable from FA, yet genetically independent of all known candidate genes. Genetic mapping is required for research into the causal gene and an understanding of the disease's physiopathologic mechanisms.
 ...
PMID:Genetic analysis of early onset cerebellar ataxia with retained tendon reflexes in four Tunisian families. 1129 81

Ataxia with vitamin E (Vit E) defciency (AVED) is an autosomal recessive disorder caused by mutations of the alpha tocopherol transfer protein gene. The Friedreich ataxia phenotype is the most frequent clinical presentation. In AVED patients, serum Vit E levels are very low in the absence of intestinal malabsorption. As Vit E is a major antioxidant agent, Vit E deficiency is supposed to be responsible for the pathological process. Twenty-four AVED patients were fully investigated (electromyography, nerve conduction velocity (NVC) studies, somatosensory evoked potentials, cerebral computed tomography scan, sural nerve biopsy, genetic studies) and supplemented with Vit E (800 mg daily) during a 1-year period. Clinical evaluation was mainly based on the Ataxia Rating Scale (ARS) for cerebellar ataxia assessment and serum Vit E levels were monitored. Serum Vit E levels normalized and ARS scores decreased moderately but significantly suggesting clinical improvement. Better results were noted with mean disease duration < or = 15 years. Reflexes remained abolished and posterior column disturbances unchanged. Vitamin E supplementation in AVED patients stabilizes the neurological signs and can lead to mild improvement of cerebellar ataxia, especially in early stages of the disease.
 ...
PMID:Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. 1155 13