Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the detection of vitamin E in 1922, nearly 50 years passed until the recognition that there is a pathogenic vitamin E deficiency in humans. Such a deficiency can be found mostly in a disturbed resorption or transport of the vitamin (mucoviscidosis, chronic cholestasis, abetalipoproteinaemia) and leads typically to a progredient spinocerebellar ataxia in combination with a polyneuropathy. Substitution of the vitamin may hinder a further progression or even lead to an amelioration of the symptoms. Prophylactic treatment in abetalipoproteinaemia prevents the otherwise unavoidable neurological deficits. Isolated vitamin E deficiency is a rare syndrome and the causes are still obscure. We observed a 26 year old male patient with such a isolated vitamin E deficiency who was hitherto thought to suffer from Friedreich's ataxia. The clinical feature showed in addition to the "classical" symptoms of vitamin E deficiency cranial nerve involvement, perioral dystonia and pyramidal signs. Histologically (M. gastrocnemius) we saw the described typical but not specific changes (neurogenic atrophy, phosphatase-positive vacuoles with myelin bodies, cores). An oral vitamin E resorption test yielded a very shortened serum half life. These results support the hypothesis that in the pathophysiology of isolated vitamin E deficiency malelimination plays an important role in addition the known malresorptions models.
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PMID:[Isolated vitamin E deficiency]. 259

Serum vitamin E concentrations and vitamin E:cholesterol ratios in 31 patients with Friedreich's ataxia were not significantly different from values obtained from either disabled or ambulant control subjects. Although the clinical features of Friedreich's ataxia are similar to those associated with severe vitamin E deficiency, there are subtle but important clinical and neurophysiological differences between the two disorders.
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PMID:Serum vitamin E concentrations are normal in Friedreich's ataxia. 358 88

A 30-year-old woman was thought to have Friedreich's disease because of progressive ataxia, dysarthria, and titubation from age 3 years. Her diet was normal, and there were neither symptoms nor laboratory evidence of liver disease or fat malabsorption. Serum vitamin E content and the ratio of serum vitamin E to total serum lipid were very low, but serum vitamin A, cholylglycine, and lipid levels were normal, as was an oral vitamin E tolerance test. Muscle biopsy showed the lysosomal inclusions of vitamin E deficiency. Mitochondria had normal oxidative phosphorylation using polarographic assays. The cause of her vitamin E deficiency was unknown.
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PMID:Friedreich's disease: V. Variant form with vitamin E deficiency and normal fat absorption. 379 40

Brain-stem auditory evoked potentials (BAEPs) were recorded in 23 children who had signs of brain-stem or cerebellar dysfunction. In patients with brain-stem gliomas, BAEPs were abnormal in all except one, in whom involvement of the brain-stem auditory pathway was limited to the midbrain tectum. The BAEPs were normal in neuronal ceroid lipofuscinosis, but abnormal bilaterally in inheritable leukoencephalopathies. All patients with Leigh's encephalopathy had BAEP abnormalities; in two, abnormalities occurred before the appearance of lesions on computed tomographic scan. Patients with Friedreich's ataxia and giant axonal dystrophy had abnormal BAEPs, but the test was normal in a child with similar neurologic findings with vitamin E deficiency. Patients with diffuse metabolic encephalopathies had variable findings. Thus, BAEP abnormalities are nonspecific for various disease processes but are frequently seen in neoplastic and neurodegenerative diseases, with primary white matter or extensive brain-stem involvement.
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PMID:Brain-stem auditory evoked potentials in children with brain-stem or cerebellar dysfunction. 397 45

Neurological syndromes similar to those associated with abetalipoproteinaemia or Friedreich's ataxia developed in four patients with chronic steatorrhoea, two of whom had cystic fibrosis and two chronic cirrhosis of childhood. Serum concentrations of vitamin E were virtually undetectable in all four patients. Substantial clinical improvement occurred in one patient after restoration of normal vitamin E levels by parenteral therapy. The findings suggest that spinocerebellar degeneration may be secondary to severe and prolonged vitamin E deficiency.
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PMID:Association of spinocerebellar disorders with cystic fibrosis or chronic childhood cholestasis and very low serum vitamin E. 611 19

The most common autosomal recessive ataxia is Friedreich's ataxia (FA), characterized mainly by an early onset, absent tendon reflexes, deep sensory loss, cerebellar and Babinski signs. Screening the patients from families with classical FA features, we found that some families were excluded from the FA locus on chromosome 9, and are associated to isolate vitamin E deficiency. The similarity of the clinical data between FA with and without vitamin E deficiency was remarkable. The disorder with vitamin E deficiency often confused with FA, is currently known as linked to chromosome 8q. Therefore it is important to test vitamin E levels in all patients suspected to have FA, since the alpha tocopherol supplementation may be efficient in early stages of the disease.
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PMID:Friedreich's ataxia-vitamin E responsive type. The chromosome 8 locus. 761 93

Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich ataxia. This disorder has been reported previously as familial isolated vitamin E deficiency. We have mapped recently the AVED locus to a 5-cM confidence interval on chromosome 8q by homozygosity mapping in six Mediterranean families. We have now analyzed six new and two previously described families and demonstrate genetic homogeneity despite important clinical variability and wide geographic origins. Analysis of nine new tightly linked microsatellite markers, including four characterized in this study, revealed a predominant but not unique mutation in northern African populations, where this condition is more frequent. Haplotype analysis but also classical recombinations allowed us to refine the AVED position to a 1-cM interval. A YAC contig over this interval was constructed from marker STSs and YAC fingerprint data, in order to facilitate the search of the AVED gene.
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PMID:Ataxia with vitamin E deficiency: refinement of genetic localization and analysis of linkage disequilibrium by using new markers in 14 families. 772 67

This review summarizes recent advances that have taken place in the field of inherited ataxias. There is increasing understanding of these disorders, primarily because of advances in the field of molecular genetics. Although the Friedreich's ataxia gene has not been cloned yet, there is increasing information about the precise location of this mutation. The chromosomal location for a distinct type of recessive ataxia associated with vitamin E deficiency was discovered. An adult- onset Friedreich's phenotype may result from a gene abnormality of the same locus as classic Friedreich's ataxia. Two distinct types of dominantly inherited ataxic syndromes are due to different trinucleotide repeat mutations, one on chromosome 6 (spinocerebellar ataxia type 1) and another on chromosome 12 (dentatorubropallidoluysian atrophy). The genes for Machado-Joseph disease as well as for a distinct type of dominantly inherited ataxia originally described from Cuba were mapped to chromosome 14 and chromosome 12, respectively. Advances were made in defining the imaging abnormalities seen in different types of ataxias.
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PMID:Degenerative ataxias. 795 39

Linkage studies with DNA polymorphic markers allowed to map the loci of three inherited ataxia and to explore genetic heterogeneity in inherited ataxia in general. The locus of Friedreich ataxia, the most frequent of all recessive ataxias, has been mapped in 9q13-q21. In addition, Friedreich ataxia is an homogeneous genetic entity since all families from all populations tested (mainly European, North-American and from the Mediterranean basin) show linkage with this locus. But the severity of the disease varied in a few families. A form of recessive ataxia associated with a selective and severe serum vitamin E deficiency, which frequently presents clinically like typical Friedreich ataxia, is not linked to 9q13-q21 markers. The autosomal recessive spastic ataxia from Charlevoix-Saguenay (a region of Quebec) is also not linked to these markers. Both entities are therefore distinct genetically from Friedreich ataxia. Among dominant ataxias, the most important group is olivo-ponto-cerebellar ataxia which is heterogeneous and for which any classification is hindered by important intra-familial variability. This group corresponds to at least three distinct loci, two of which have been mapped, one in 6p23-p24, and the other, more recently, on chromosome 12. Prenatal and presymptomatic diagnosis based on linked markers can be made for the three mapped ataxias, but only in families with an affected individual for whom the diagnosis has been ascertained by through clinical investigation or by linkage analysis if the family is large enough (mainly for the dominant diseases). Linked markers are also the first tools for the search of the defective genes by positional cloning.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Molecular genetics and familial ataxia]. 809 Oct 82

Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative disorder, the disease locus (FRDA) of which has been assigned to 9q13-q21.1 by genetic linkage analysis in affected families. We report two large inbred Tunisian families with FA manifestations that did not show the expected linkage. The disease locus could be excluded from a large (12 cMo) region around FRDA. This is the first report providing evidence for nonallelic genetic heterogeneity for the FA clinical phenotype. On subsequent analysis, all patients had very low levels of serum vitamin E whereas the parents and healthy sibs had normal vitamin E levels. This establishes that the selective vitamin E deficiency with normal fat absorption is an autosomal recessive trait, which is associated in the two families reported here with the FA phenotype.
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PMID:Friedreich's ataxia phenotype not linked to chromosome 9 and associated with selective autosomal recessive vitamin E deficiency in two inbred Tunisian families. 823 22


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