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)

The authors present a case of diffuse axonal injury (DAI) treated by cervical spinal cord stimulation (C-SCS) for gait disturbance. The patient had right hemiparesis of moderate degree, mild ataxia, ideational apraxia and gait disturbance, when admitted to our hospital for rehabilitation. He could not walk by himself, nevertheless neurorehabilitation was done for four months. Xenon-CT was examined by C-SCS loading and the changes of regional cerebral blood flow were significantly increased in both hemispheres, especially in the thalamus. C-SCS was performed continuously on condition of 25 Hz, 200 microsec and 0.5 V, daily for a month. Neurological deficits, especially gait disturbance due to ideational apraxia, were gradually improved after initiation of C-SCS, and the patient could walk by himself. We speculate that C-SCS played a role in triggering improvement of gait disturbance at the chronic stage in our case, and SCS may be helpful for neurorehabilitation of focal symptoms after DAI.
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PMID:Successful treatment by spinal cord stimulation for gait disturbance in a patient with diffuse axonal injury. 1451 23

A 14-year-old girl, homozygous for an insertion mutation of aprataxin (APTX), 689 ins T, is described. She presented with severe generalized dystonia, ataxia, ocular motor apraxia, and areflexia. The dystonia of this patient suggests involvement of the basal ganglia or thalamus, along with clinical diversity in this disorder.
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PMID:Severe generalized dystonia as a presentation of a patient with aprataxin gene mutation. 1453 29

There has been a recent explosion in knowledge regarding the genetic basis of several autosomal recessive ataxias. This article summarizes current information regarding rare forms of recessive ataxias. Friedreich's ataxia and ataxia telangiectasia are dealt with in other articles in this issue. The rarer recessive ataxias can be clinically classified as sensory and spinocerbellar ataxias, cerebellar ataxia with sensory-motor polyneuropathy, and purely cerebellar ataxias. Examples of the first category include ataxia with isolated vitamin E deficiency, abetalipoproteinemia, Refsum's disease, infantile-onset spinocerebellar ataxia, and ataxia with blindness and deafness. Examples of ataxia with sensory-motor polyneuropathy include ataxia with oculomotor apraxia 1 and 2 and spinocerebellar ataxia with neuropathy 1. Examples of purely cerebellar ataxia include autosomal recessive spastic ataxia of Charlevoix-Saguenay and ataxia with hypogonadotropic hypogonadism. This review summarizes the clinical and genetic features of these entities and concludes that the pathogenic basis of such ataxias at this time appear to involve two broad types of processes: free-radical injury and defects of DNA single- or double-strand break repair.
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PMID:Rare forms of autosomal recessive neurodegenerative ataxia. 1465 6

Ataxia with oculomotor apraxia type 2 (AOA2) is a newly described autosomal recessive cerebellar ataxia (ARCA) defined by genetic location to 9q34 of three families sharing gait ataxia, oculomotor apraxia and/or elevated alpha-foetoprotein (AFP) levels. We have evaluated 77 families with progressive non-Friedreich ARCA and have identified six families with a phenotype suggestive of AOA2. Linkage was confirmed in all six families, with a maximal lod score of 5.91 at D9S1830. We report the first detailed phenotypic study, including neuropsychological, oculographic and brain imaging investigations, in the largest series of AOA2 patients yet recruited. The mean age at onset was 15.1 +/- 3.8 years. Sensory motor neuropathy (92%) and choreic or dystonic movements (44%) were frequent. Oculomotor apraxia was observed in 56% of patients and characterized by increased horizontal saccade latencies and hypometria. AFP levels were elevated in 100% of the families, making it a useful biological marker. This study shows for the first time that AOA2 can be found in Europe, North Africa and the West Indies, and its relative frequency represents approximately 8% of non-Friedreich ARCA, which is more frequent than ataxia telangiectasia and ataxia with oculomotor apraxia type 1 (AOA1), in our series of adult patients. In adults, AOA2 may be, therefore, the most frequent cause of ARCA identified so far, after Friedreich's ataxia.
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PMID:Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. 1473 55

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is an autosomal recessive neurodegenerative disorder characterized by early-onset ataxia, ocular motor apraxia, and hypoalbuminemia. Recently, the causative gene for EAOH, APTX, has been identified. Of the two splicing variants of APTX mRNA, the short and the long forms, long-form APTX mRNA was found to be the major isoform. Aprataxin is mainly located in the nucleus, and, furthermore, the first nuclear localization signal located near the amino terminus of the long-form aprataxin is essential for its nuclear localization. We found, based on the yeast two-hybrid and coimmunoprecipitation experiments, that the long-form but not the short-form aprataxin interacts with XRCC1 (x-ray repair cross-complementing group 1). Interestingly the amino terminus of the long-form aprataxin is homologous with polynucleotidekinase-3'-phosphatase, which has been demonstrated to be involved in base excision repair, a subtype of single-strand DNA break repair, through interaction with XRCC1, DNA polymerase beta, and DNA ligase III. These results strongly support the possibility that aprataxin and XRCC1 constitute a multiprotein complex and are involved in single-strand DNA break repair, and furthermore, that accumulation of unrepaired damaged DNA underlies the pathophysiological mechanisms of EAOH.
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PMID:Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein. 1475 28

Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.
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PMID:Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. 1477 Jan 81

Ataxia-oculomotor apraxia (AOA1) is a neurological disorder with symptoms that overlap those of ataxia-telangiectasia, a syndrome characterized by abnormal responses to double-strand DNA breaks and genome instability. The gene mutated in AOA1, APTX, is predicted to code for a protein called aprataxin that contains domains of homology with proteins involved in DNA damage signalling and repair. We demonstrate that aprataxin is a nuclear protein, present in both the nucleoplasm and the nucleolus. Mutations in the APTX gene destabilize the aprataxin protein, and fusion constructs of enhanced green fluorescent protein and aprataxin, representing deletions of putative functional domains, generate highly unstable products. Cells from AOA1 patients are characterized by enhanced sensitivity to agents that cause single-strand breaks in DNA but there is no evidence for a gross defect in single-strand break repair. Sensitivity to hydrogen peroxide and the resulting genome instability are corrected by transfection with full-length aprataxin cDNA. We also demonstrate that aprataxin interacts with the repair proteins XRCC1, PARP-1 and p53 and that it co-localizes with XRCC1 along charged particle tracks on chromatin. These results demonstrate that aprataxin influences the cellular response to genotoxic stress very likely by its capacity to interact with a number of proteins involved in DNA repair.
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PMID:Aprataxin, a novel protein that protects against genotoxic stress. 1504 83

This case report describes three separate episodes of isolated ataxia, hallucinations of being accompanied by another person, and bilateral dressing apraxia occurring in a single individual without prior warning signs. These symptoms are attributable to disruption of vestibular processing in the temporoparietal cortex or associated limbic structures. Neurological dysfunction at high altitude is usually ascribed to high altitude cerebral edema or acute mountain sickness. However, transient neurological symptoms occur abruptly at more extreme altitudes, often following vigorous exertion, without overt altitude-induced prodromes. These symptoms may be caused by intense neuronal discharge or neuronal synchronization as a feature of epileptic discharges or cortical spreading depression. Transient high altitude neurological dysfunction should be recognized as a separate complication of extreme altitude, distinct from high altitude cerebral edema.
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PMID:Transient high altitude neurological dysfunction: an origin in the temporoparietal cortex. 1507 18

In neurodevelopmental disorders, the characteristic symptoms appear age-dependently along with the functional and morphological development of the affected neurons and the neuronal pathways. Most of them have the primary lesion in the subcortical structures as these mature earlier, which include the aminergic neurons of the brainstem and the midbrain having important roles for development of the higher cortical function (HCF). Thus, to clarify the pathophysiologies of the symptoms appearing age-dependently makes it possible to demonstrate the process of development of the HCF. Here, I reviewed the characteristic symptoms and their pathophysiologies of Rett syndrome, DYT-1, autosomal dominant GTP cyclohydrolase I (ADGCH I) deficiency, Tourette syndrome (TS) and Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), and suggested that the brainstem aminergic neurons modulating the locomotion have roles for development of the frontal cortex, the dopaminergic neurons and basal ganglia pathways involving in the action dystonia for motor execution and the serotonergic and the dopaminergic neurons projectioning to the nonmotor basal ganglia thalamocortical circuits for development of the frontal area, the targets of the circuits. While, postural dystonia, tics in GTS and symptoms in EAOH reflect the development of the causative neurons and the neuronal systems.
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PMID:[Visual child neurology]. 1515 53

Aprataxin (APTX) mutations are the cause of ataxia with ocular motor apraxia type 1(AOA1), an autosomal recessive disorder linked to chromosome 9p13.AOA1 seems to be one of the most frequent causes of recessive ataxia in Japan and Portugal. We screened a group of 165 early onset ataxia patients for APTX mutations and detected two non-related patients homozygous for the W293X nonsense mutation. Additionally, we describe several new transcript variants of the APTX gene and discuss their relevance for a sufficient mutation screening.
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PMID:Aprataxin mutations are a rare cause of early onset ataxia in Germany. 1516 93


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