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)

Local cerebral metabolic rate for glucose was studied with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 22 patients with Friedreich's ataxia and 23 age-matched normal control subjects. The diagnosis of Friedreich's ataxia was established by the history and physical findings and by excluding other diseases through laboratory investigations. PET studies revealed a statistically significant widespread increase of local cerebral metabolic rate for glucose in the brains of patients with Friedreich's ataxia who were still ambulatory, in comparison with normal control subjects. Nonambulatory patients with Friedreich's ataxia, in comparison with normal control subjects, had significantly increased local cerebral metabolic rates for glucose in the caudate and lenticular nuclei, but not in the other structures studied. The rate was significantly greater in ambulatory patients with Friedreich's ataxia than in nonambulatory patients in all structures studied except the caudate and lenticular nuclei. The data suggest that early in the course of Friedreich's ataxia, the local cerebral metabolic rate for glucose is increased extensively in the central nervous system, and as the disease progresses, it decreases in a regionally specific manner.
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PMID:Cerebral glucose hypermetabolism in Friedreich's ataxia detected with positron emission tomography. 228 62

A family with two members who had early-onset cerebellar ataxia (EOCA) with retained tendon reflexes had, in addition to their motor deficits, a progressive impairment of cognitive and visuospatial abilities. We used positron emission tomography (PET) with 11C-flumazenil to study gamma-aminobutyric type A/benzodiazepine receptor binding (BZR) and 18F-2-fluoro-2-deoxy-D-glucose to analyze longitudinally regional cerebral glucose metabolism. Flumazenil-PET demonstrated loss of BZR binding that has not been shown in Friedreich's ataxia and olivopontocerebellar atrophy. These findings may be useful for differentiation of EOCA from other types of cerebellar ataxia. In comparison to age-matched control subjects, these patients showed a global metabolic decline and predominant hypometabolism in the thalamus and cerebellum. The progressive metabolic derangement may be explainable by a disturbed integrity of cognition-related networks resulting from secondary degeneration of cerebello-thalamo-cortical projections.
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PMID:Early-onset cerebellar ataxia (EOCA) with retained reflexes: reduced cerebellar benzodiazepine-receptor binding, progressive metabolic and cognitive impairment. 968 85

The mitochondrial matrix protein frataxin is depleted in patients with Friedreich's ataxia, the most common autosomal recessive ataxia. While frataxin is important for intracellular iron homeostasis, its exact cellular role is unknown. Deletion of the yeast frataxin homolog YFH1 yields mutants ((Delta)yfh1) that, depending on the genetic background, display various degrees of phenotypic defects. This renders it difficult to distinguish primary (early) from secondary (late) consequences of Yfh1p deficiency. We have constructed a yeast strain (Gal-YFH1) that carries the YFH1 gene under the control of a galactose-regulated promoter. Yfh1p-deficient Gal-YFH1 cells are far less sensitive to oxidative stress than (Delta)yfh1 mutants, maintain mitochondrial DNA, and synthesize heme at wild-type rates. Yfh1p depletion causes a strong reduction in the assembly of mitochondrial Fe/S proteins both in vivo and in detergent extracts of mitochondria. Impaired Fe/S protein biogenesis explains the respiratory deficiency of Gal-YFH1 cells. Furthermore, Yfh1p-depleted Gal-YFH1 cells show decreased maturation of cytosolic Fe/S proteins and accumulation of mitochondrial iron. This latter phenotype is common for defects in cytosolic Fe/S protein assembly. Together, our data demonstrate a specific role of frataxin in the biosynthesis of cellular Fe/S proteins and exclude most of the previously suggested functions. Friedreich's ataxia may therefore represent a disorder caused by defects in Fe/S protein maturation.
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PMID:The yeast frataxin homolog Yfh1p plays a specific role in the maturation of cellular Fe/S proteins. 1216 64

Expansions of simple DNA repeats cause numerous hereditary disorders in humans. Replication, repair, and transcription are implicated in the expansion process, but their relative contributions are yet to be distinguished. To separate the roles of replication and transcription in the expansion of Friedreich's ataxia (GAA)n repeats, we designed two yeast genetic systems that utilize a galactose-inducible GAL1 promoter but contain these repeats in either the transcribed or nontranscribed region of a selectable cassette. We found that large-scale repeat expansions can occur in the lack of transcription. Induction of transcription strongly elevated the rate of expansions in both systems, indicating that active transcriptional state rather than transcription through the repeat per se affects this process. Furthermore, replication defects increased the rate of repeat expansions irrespective of transcriptional state. We present a model in which transcriptional state, linked to the nucleosomal density of a region, acts as a modulator of large-scale repeat expansions.
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PMID:Coupling transcriptional state to large-scale repeat expansions in yeast. 2546 41