Disease relevance of Friedreich Ataxia

• Familial myoclonic epilepsy with ataxia and neuropathy with additional features of Friedreich's ataxia and peroneal muscular atrophy [1].
• Fourteen patients with the clinical diagnosis of early onset cerebellar ataxia with retained tendon reflexes (EOCA) were examined and compared with 11 patients with Friedreich's ataxia (FA) [2].
• The Friedreich's ataxia mutation was found in five patients (4%), the spinocerebellar ataxia (SCA) 2 mutation in one (1%), the SCA3 mutation in two (2%) and the SCA6 mutation in seven (6%) [3].
• Yfh1p is homologous to frataxin, the human protein implicated in the neurodegenerative disease, Friedreich's ataxia [4].
• Nineteen control subjects, 25 patients with multiple sclerosis (MS) and 4 patients with Friedreich's ataxia (FA) were tested [5].

Psychiatry related information on Friedreich Ataxia

• The authors found allele sizes within the proposed pathogenic range in three patients with ataxia of unknown etiology, in two individuals from pedigrees with either SCA2 or Friedreich's ataxia, and in two patients with Alzheimer's disease [6].
• Alzheimer-type dementia, amyotrophic lateral sclerosis, Down's syndrome, epilepsy, Friedreich's ataxia, Guillaine-Barré syndrome, hepatic encephalopathy, multiple sclerosis, Parkinson's disease, Pick's disease, retinitis pigmentosa, retinal dystrophy, schizophrenia, and Wernicke-Korsakoff syndrome [7].
• Huntington's disease (HD) and Friedreich's ataxia (FRDA) are associated with defects of respiratory-chain enzyme activities [8].

High impact information on Friedreich Ataxia

• Friedreich's ataxia (FRDA) is an autosomal recessive degenerative disorder that primarily affects the nervous system and heart [9].
• The Friedreich's ataxia gene encodes a novel phosphatidylinositol-4- phosphate 5-kinase [10].
• Low activities of the pyruvate and oxoglutarate dehydrogenase complexes in five patients with Friedreich's ataxia [11].
• GAA instability in Friedreich's Ataxia shares a common, DNA-directed and intraallelic mechanism with other trinucleotide diseases [12].
• In Friedreich's ataxia (FRDA), the most common type of autosomal recessive ataxia, the loss of a mitochondrial protein, frataxin, results in overload of mitochondrial iron and oxidative stress [13].

Chemical compound and disease context of Friedreich Ataxia

• On the basis of these results, we assessed the effect of idebenone (a free-radical scavenger) in three patients with Friedreich's ataxia [14].
• 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 [15].
• We have determined mitochondrial ATP, phosphocreatine, and intracellular inorganic phosphate levels by 31P nuclear magnetic resonance spectroscopy in the heart of 11 Friedreich's ataxia patients and 11 healthy controls [16].
• Proteomic analysis of the mutant yeast model of Friedreich ataxia presented in this paper reveals that these cells display increased amounts of proteins involved in antioxidant defenses, including manganese-superoxide dismutase [17].
• Manganese Is the Link between Frataxin and Iron-Sulfur Deficiency in the Yeast Model of Friedreich Ataxia [17].

Biological context of Friedreich Ataxia

• In families with Friedreich's Ataxia, the only recessive trinucleotide disease, GAA instability is not a function of the number of long alleles, ruling out homologous recombination or gene conversion as a major mechanism [12].
• 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 [18].
• Fragile X mental retardation and Friedreich's ataxia were among the first pathogenic trinucleotide repeat disorders to be described in which noncoding repeat expansions interfere with gene expression and cause a loss of protein production [19].
• Up-regulation of c-Jun N-terminal kinase pathway in Friedreich's ataxia cells [20].
• In contrast, in one family with typical Friedreich's ataxia phenotype we did not find an expanded allele; this suggests that there can be either point mutations in the X25 gene on both chromosomes or locus heterogeneity in Friedreich's ataxia [21].

Anatomical context of Friedreich Ataxia

• Pyruvate carboxylase activity is not abnormal in fibroblasts of patients with Friedreich's ataxia [22].
• 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 [15].
• Frataxin gene of Friedreich's ataxia is targeted to mitochondria [23].
• Absence of lower limb tendon reflexes has been considered an essential diagnostic criterion for Friedreich's ataxia (FA) [24].
• Skeletal muscle NAD+(P) and NADP+-dependent malic enzyme in Friedreich's ataxia [25].

Gene context of Friedreich Ataxia

• CCC1 suppresses mitochondrial damage in the yeast model of Friedreich's ataxia by limiting mitochondrial iron accumulation [26].
• Mapping of the second Friedreich's ataxia (FRDA2) locus to chromosome 9p23-p11: evidence for further locus heterogeneity [27].
• Plasma lipoprotein lipase and hepatic lipase activities in Friedreich's ataxia [28].
• Pituitary responses to a neuroactive tripeptide (TRH) in Friedreich's ataxia families [29].
• Yfh1p is the yeast homolog of the human frataxin protein, which is deficient in Friedreich's ataxia [30].

Analytical, diagnostic and therapeutic context of Friedreich Ataxia

• Cerebral glucose hypermetabolism in Friedreich's ataxia detected with positron emission tomography [15].
• Genetic and sequence analysis of the FRDA gene and comprehensive laboratory examinations excluded Friedreich's ataxia and other similar recessive diseases [31].
• Age of onset, sex, and cardiomyopathy as predictors of disability and survival in Friedreich's disease: a retrospective study on 119 patients [32].
• We report the case of a 34-year-old man with Friedreich's ataxia and dilated cardiomyopathy who underwent successful cardiac transplantation [33].
• In view of this high incidence of hypertrophic cardiomyopathy, echocardiography is suggested as part of the routine evaluation of the patient with Friedreich's Ataxia [34].

References