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)

We describe the unusual case of a 51-year-old woman with spinocerebellar ataxia type 1 (SCA1) who showed choreiform movements in addition to cerebellar ataxia. To date, extrapyramidal signs including involuntary movements have been rarely reported in SCA1. Surface electromyogram in our patient revealed grouped discharges whose duration was longer than that of chorea observed in HD, indicating that the involuntary movements represented choreoathetosis rather than pure chorea. These choreiform movements have not been seen in non-hereditary spinocerebellar ataxia. Therefore, if "sporadic" cases of cerebellar ataxia show such movements, the possibility of genetic origin of the ataxia is high and a surveillance of various forms of hereditary spinocerebellar ataxia including SCA1 is required.
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PMID:Choreiform movements in spinocerebellar ataxia type 1. 1144 Jul 52

Leigh disease is a subacute neurodegenerative disorder characterized by symmetric necrotic lesions in the basal ganglia, cerebellum, thalamus, brain stem, and optical nerves and caused by altered oxidative phosphorylation. We describe the clinical, biochemical, neuroimaging, and molecular studies of a 19-year-old boy with early-onset Leigh disease manifesting as severe extrapyramidal disorder with generalized dystonia and choreoathetosis. He was born of healthy parents after an uneventful pregnancy and delivery. At the age of 2 1/2 years, after a minor respiratory infection, he developed unstable, broad-based gait and tremor of the hands. These symptoms persisted for the next several years, when ataxia became more prominent. Difficulty in swallowing, dysarthria, trunk dystonia, and marked dyskinesia of the arms and hands gradually developed. Nystagmus, transient ptosis, and strabismus also appeared. Abnormal laboratory findings included elevated plasma and cerebrospinal fluid lactate and pyruvate, with an abnormal lactate/pyruvate ratio. Cranial computed tomography and magnetic resonance imaging demonstrated signs of cerebellar atrophy, bilateral and symmetric hypodensities in the lentiform nucleus and thalamus, and transient hyperintensities of cerebral peduncles in T2-weighted sequences suggestive of Leigh disease. Muscle biopsy revealed isolated fiber atrophy, necrotic fibers undergoing phagocytosis, and no ragged-red fibers. The measured catalytic activity of cytochrome c oxidase in skeletal muscle homogenates demonstrated a partial cytochrome c oxidase deficiency No abnormalities in the mitochondrial genome and in the SURF-1 gene were found. The boy is currently receiving levodopa therapy, creatine monohydrate, and a high dosage of thiamine and lipoic acid, his condition is stabilized, and extrapyramidal symptoms are less pronounced.
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PMID:Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndrome. 1151 Sep 39

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by various combinations of cerebellar ataxia, choreoathetosis, myoclonus, epilepsy, dementia and psychiatric symptoms. With the discovery of the gene for DRPLA in 1994, molecular mechanisms of neurodegeneration has been intensively investigated. Expression of truncated DRPLA proteins in cultured cell has been shown to result in aggregate body formation and apoptosis. We have developed transgenic mice for DRPLA (Q129 mice). The Q129 mice showed a severe neurological phenotype characterized by ataxia, myoclonus and seizures. Although numerous neuronal intranuclear inclusions (NIIs) were observed in the brain, obvious neuronal loss was not observed. NIIs, however, appeared much later than the phenotypic presentations, and intranuclear accumulation (diffuse nuclear staining) of mutant proteins was the earliest phenomenon. These results suggest that "neuronal dysfunction", but not "neuronal cell death", is responsible for the phenotypes. Hypothesizing that nuclear proteins interacting with expanded polyglutamine stretches are involved in the pathogenesis, we found that that expanded polyglutamine stretches preferentially bind to TAF130, a cofactor involved in CREB-dependent transcriptional activation, and strongly suppressed CREB-dependent transcriptional activation. Taken together, these findings suggest that the interference of CREB-dependent transcription by expanded polyglutamine stretches is involved in the neuronal dysfunction in polyglutamine diseases.
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PMID:[Molecular mechanisms of neurodegeneration in dentatorubral-pallidoluysian atrophy (DRPLA)]. 1223 96

The paroxysmal dyskinesias (PxDs) are involuntary, intermittent movement disorders manifested by dystonia, chorea, athetosis, ballismus or any combination of these hyperkinetic disorders. Paroxysmal kinesigenic dyskinesia (PKD), one of the four main types of PxD, involves sudden attacks of dyskinesias induced by voluntary movements. PKD most commonly occurs sporadically or as an autosomal-dominant familial trait with variable penetrance. Many causes of secondary PKD are being recognized. The exact pathophysiology of the PxDs awaits further elucidation, although basal ganglia dysfunction appears to play a major role. Although the precise gene remains unknown, genetic linkage studies have isolated loci on chromosome 16, which colocalizes with the locus for familial infantile convulsions and paroxysmal choreoathetosis in some studies. The episodic nature of PKD and its relationship with other episodic diseases, such as epilepsy, migraine, and episodic ataxia, suggests channelopathy as a possible underlying etiology. PKD may remit spontaneously, but it also responds well to anticonvulsants as well as some other agents.
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PMID:Paroxysmal kinesigenic dyskinesias. 1278 50

Dentatorubropallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by a variable combination of progressive ataxia, epilepsy, myoclonus, choreoathetosis and dementia. This disease is caused by a (CAG)(n) expansion in the DRPLA gene, on chromosome 12p13. DRPLA is prevalent in Japan, but several families of non-Japanese ancestry have already been published. To identify the origin of expanded alleles in Portuguese families with DRPLA, we studied two previously reported intragenic SNPs in introns 1 and 3, in addition to the CAG repeat of the DRPLA gene. The results showed that all four Portuguese DRPLA families shared the same haplotype, which is also common to that reported for Japanese DRPLA chromosomes. This haplotype is also the most frequent in Japanese normal alleles, whereas it was rare in Portuguese control chromosomes. Thus, our findings support that a founder DRPLA haplotype of Asian origin was introduced in Portugal, being responsible for the frequency of the disease in this country.
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PMID:Portuguese families with dentatorubropallidoluysian atrophy (DRPLA) share a common haplotype of Asian origin. 1451 72

Per year, approximately 1,000 children in Germany suffer from brain damage due to hypoxic-ischemic insults during the perinatal period. Based on the severity and localization of the insult, these children develop either spastic pareses, choreoathetosis, ataxia, or sensomotoric dysfunctions. A close cooperation between obstetricians, pediatricians, neuropediatricians, physical therapists, developmental psychologists, and other specialists is required, as the strain these disorders have on the children and their families is tremendous. The costs resulting per birthyear for the community are estimated on 1 million Euro. Clinical concepts to decrease the cerebral morbidity in perinatology departments have proven to be effective over the last decade. However, since brain damage cannot be prevented every time, it is essential that therapeutic measures, which have a neuroprotective effect after the insult, are being developed. Experimental pilots regarding these matters are promising. Current experiments are focused on the possible application of cord blood-derived stem cells for neuroregeneration.
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PMID:[Perinatal brain damage--from neuroprotection to neuroregeneration using cord blood stem cells]. 1499 98

Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder, with onset in early childhood and a frequency of approximately 1 in 40,000 births in the United States. A-T is seen among all races and is most prominent among ethnic groups with a high frequency of consanguinity. The syndrome includes: progressive cerebellar ataxia, dysarthric speech, oculomotor apraxia, choreoathetosis and, later, oculocutaneous telangiectasia. Immunodeficiency with sinopulmonary infections, cancer susceptibility (usually lymphoid), and sensitivity to ionizing radiation are also characteristic. Laboratory findings include: (1) elevated alphafetoprotein (AFP), (2) cerebellar atrophy on magnetic resonance imaging, (3) reciprocal translocations between chromosomes 7 and 14 in lymphocytes, (4) absence or dysfunction of the ATM protein, (5) radiosensitivity, as demonstrated by colony survival assay (CSA), and (6) mutations in the ATM gene. The latter are usually truncating or splicing mutations; approximately 10% are missense mutations. Mutations are found across the entire gene. Almost all recurring mutations are found on unique haplotypes that represent founder effects and ancestral relationships between patients. In addition to radiosensitivity and sensitivity to radiomimetic chemicals, the phenotype of A-T cells includes defective damage-induced activation of the cell cycle checkpoints at G1, S and G2/M. With the aid of molecular testing, A-T can now be distinguished from other autosomal recessive cerebellar ataxias (ARCAs) such as Friedreich ataxia, Mre11 deficiency (AT-like disease), and the oculomotor apraxias 1 (aprataxin deficiency) and 2 (senataxin deficiency). Other "A-T variants" include: (1) Nijmegen breakage syndrome (NBS) or nibrin/Nbs1 deficiency, with microcephaly and mental retardation but without ataxia, apraxia, or telangiectasia, and 2) A-T(Fresno), a phenotype that combines features of both NBS and A-T, with mutations in the ATM gene. The term "A-T variant" has a diminishing usefulness.
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PMID:Ataxia-telangiectasia, an evolving phenotype. 1527 7

Glucose transport protein deficiency due to mutation in the GLUT1 gene is characterized by infantile onset and chronic seizure disorder, microcephaly, global developmental delays, and hypoglycorrhachia. We describe a 10-year-old normocephalic male with prominent ataxia, dystonia, choreoathetosis, and GLUT1 deficiency whose motor abnormalities improved with a ketogenic diet. We illustrate the motor abnormalities, at baseline and after ketogenic diet, that characterize this unusual case. This case broadens the phenotype of GLUT1 deficiency and illustrates the importance of cerebrospinal fluid (CSF) evaluation in detecting potentially treatable conditions in children with undiagnosed movement disorders.
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PMID:Atypical GLUT1 deficiency with prominent movement disorder responsive to ketogenic diet. 1614 86

A 48-year-old man developed progressive hemidystonia and postural impairment with falls, followed by choreoathetosis, hyporeflexia, ataxia, supranuclear vertical gaze palsy, and dementia, lasting only 3.5 years from symptom onset to death. Family history and genetic testing were unrevealing. Neuropathology showed findings identical to genetic dentatorubral pallidoluysian atrophy (DRPLA), except for the absence of intranuclear inclusions and the presence of intracytoplasmic inclusions in the pons, striatum, thalamus, and subthalamic nucleus. This case expands the clinical and neuropathological spectrum of DRPLA and supports the hypothesis that aggregates may not be intrinsically pathogenic.
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PMID:Rapidly progressive sporadic dentatorubral pallidoluysian atrophy with intracytoplasmic inclusions and no CAG repeat expansion. 1707 58

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by various combinations of myoclonus epilepsy, ataxia, choreoathetosis and dementia. No specific therapy has been established and renal complication is rare. We report two cases of DRPLA with renal complications. Hematuria and proteinuria had gradually progressed for 2 and 13 years in these patients. Renal biopsy findings revealed focal glomerulosclerosis in one case and end-stage kidney disease in the other case. Angiotensin-converting enzyme inhibitor and angiotensin receptor II antagonist were administered to both patients, resulting in improved proteinuria and preserved renal function in one patient, while renal function continued to deteriorate in the other patient. Although renal complication is rare in patients with DRPLA, the presence of renal disease has to be suspected in patients with persistent proteinuria.
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PMID:Renal complications in two patients with dentatorubral-pallidoluysian atrophy. 1726 99


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