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)

Ten of 100 mature ewes were afflicted with acute oxalate toxicosis within 40 hours after being temporarily penned in a lot that contained considerable growing Rumex crispus (curly dock). Clinical signs of toxicosis included excess salivation, tremors, ataxia, and recumbency. Affected ewes were markedly hypocalcemic and azotemic. Oxalate crystals were not observed in urine. Gross postmortem lesions were minimal and nondiagnostic in 2 ewes that died peracutely, but perirenal edema and renal tubular degeneration were clearly observable in ewes euthanatized on the third day of toxicosis. Diagnosis of oxalate toxicosis was confirmed by histopathologic findings. Samples of Rumex spp contained 6.6 to 11.1% oxalic acid on a dry-weight basis, a concentration comparable with that in other oxalate-containing plants that have caused acute oxalate toxicosis.
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PMID:Acute oxalate poisoning attributable to ingestion of curly dock (Rumex crispus) in sheep. 236 22

A 66-year-old man was admitted to Tokyo Metropolitan Geriatric Hospital because of progressive speech disturbance and ataxic gait. He had no history of abdominal surgery, liver disease, heavy drinking nor blood transfusion. One day before the admission, he showed confusional behavior for 6 hours, but he had no other history of consciousness disturbance. Neurological examination revealed slurred speech, fixation nystagmus, limb and gait ataxia, and hyperreflexia with pathological reflexes. Extrapyramidal signs were not identified. Laboratory examination showed marked hyperammonemia (118-292 micrograms/dl) with poor ICG excretion (ICG15 min = 30.8%). Percutaneous portography showed a large shunt vessel between the portal vein and the left hepatic vein. The plasma ammonium level of the right hepatic vein is normal (15 micrograms/dl), but that of the left one is very high (298 micrograms/dl). Therefore we concluded that hyperammonemia of the systemic circulation was resulted from portal-systemic shunt. A T2 weighted MRI image demonstrated symmetrical high signal intensity in the deep cerebral white matter. Unique lesions were observed in the bilateral middle cerebellar peduncles, and shown as low signal intensity in T1 weighted image and as high signal intensity in T2 weighted image. Hyperammonemia and neurological impairments of this patient did not improve with medical treatment. Three months after occlusion of the shunt vessel, fixation nystagmus and extensor plantar responses abolished and unsteadiness gait improved. Hyperammonemia might cause the cerebellar ataxia in the present case.
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PMID:[A case of portal-systemic shunt with progressive ataxia]. 833 93

Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO). Due to the clinical heterogeneity, time-dependent evolution of symptoms, overlapping phenotypes, and inconsistencies in muscle pathology findings, definitive diagnosis relies on the molecular finding of deleterious mutations. We sequenced the exons and flanking intron region from approximately 350 patients displaying a phenotype consistent with POLG related mitochondrial disease and found informative mutations in 61 (17%). Two mutant alleles were identified in 31 unrelated index patients with autosomal recessive POLG-related disorders. Among them, 20 (67%) had Alpers syndrome, 4 (13%) had arPEO, and 3 (10%) had ANS. In addition, 30 patients carrying one altered POLG allele were found. A total of 25 novel alterations were identified, including 6 null mutations. We describe the predicted structural/functional and clinical importance of the previously unreported missense variants and discuss their likelihood of being pathogenic. In conclusion, sequence analysis allows the identification of mutations responsible for POLG-related disorders and, in most of the autosomal recessive cases where two mutant alleles are found in trans, finding deleterious mutations can provide an unequivocal diagnosis of the disease.
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PMID:Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. 1854 65

The fragile X mental retardation 1 gene (FMR1), which codes for the fragile X mental retardation 1 protein (FMRP), is located at Xp27.3. The normal allele of the FMR1 gene typically has 5 to 40 CGG repeats in the 5' untranslated region; abnormal alleles of dynamic mutations include the full mutation (> 200 CGG repeats), premutation (55-200 CGG repeats) and the gray zone mutation (45-54 CGG repeats). Premutation carriers are common in the general population with approximately 1 in 130-250 females and 1 in 250-810 males, whereas the full mutation and Fragile X syndrome (FXS) occur in approximately 1 in 4000 to 1 in 7000. FMR1 mutations account for a variety of phenotypes including the most common monogenetic cause of inherited intellectual disability (ID) and autism (FXS), the most common genetic form of ovarian failure, the fragile X-associated primary ovarian insufficiency (FXPOI, premutation); and fragile X-associated tremor/ataxia syndrome (FXTAS, premutation). The premutation can also cause developmental problems including ASD and ADHD especially in boys and psychopathology including anxiety and depression in children and adults. Some premutation carriers can have a deficit of FMRP and some unmethylated full mutation individuals can have elevated FMR1 mRNA that is considered a premutation problem. Therefore the term "Fragile X Spectrum Disorder" (FXSD) should be used to include the wide range of overlapping phenotypes observed in affected individuals with FMR1 mutations. In this review we focus on the phenotypes and genotypes of children with FXSD.
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PMID:Fragile X spectrum disorders. 2560 63

Behavioral symptoms and traits have been proposed as early markers in neurodegenerative diseases. The aim of this study was to evaluate social anxiety and autism in FMR1 premutation carriers using the Social Phobia Inventory (SPIN) and the Autism-Spectrum Quotient (AQ) questionnaires. Fifty-nine premutation carriers were compared with 50 controls. The SPIN test showed statistically significant differences between female but not male carriers. The AQ questionnaire found statistically significant differences between premutation carriers and controls in the total AQ as well as in the social skills and attention switching subdomains. A gender effect was only observed for the social skills subdomain. Spearman's correlation analysis revealed a moderately positive correlation with the total AQ scores as well as the social skills and communication subdomains. Our results show that fragile X-associated tremor/ataxia syndrome (FXTAS) patients have higher AQ scores. Moreover, this is the first study to find statistically significant differences between FXTAS and no-FXTAS premutation carriers in the communication and the imagination subdomains, suggesting that FXTAS patients present a broader autistic phenotype than premutation carriers without FXTAS. Based on our results, a wide range of behavioral/psychiatric traits should be included within the broader phenotypic presentation of individuals with the FMR1 premutation.
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PMID:Social anxiety and autism spectrum traits among adult FMR1 premutation carriers. 2710 23

We report on Gomez-Lopez-Hernandez syndrome (GLHS) in a Caucasian patient, Georgian, 36 months, male, only child born to non-consanguineous parents. There were no similar cases in the family and among close relatives. MRI study confirmed rhombencephalosynapsis (fusion of cerebellar hemispheres in combination with the agenesis of cerebellar vermis) and mild dilation of the lateral ventricles. Other main findings are bilateral parieto-temporal alopecia and brachiturricephaly (broad skull shape and tower-like elongation of the cranium in the vertical axis), low-set posteriorly retracted ears, strabismus (in the right eye), hypotonia (Beighton scale score - 6) and ataxia (trouble maintaining balance). Patient has no signs of trigeminal anesthesia, no recurrent, painless eye infections, corneal opacities and ulcerated wounds on the facial skin and buccal mucosa were observed. Based on the scientific literature we suggest a finding of brachiturricephaly in addition to rhombencephalosynapsis and bilateral alopecia sufficient to put a diagnosis of GLHS. Patient did not speak, disregarded guardians and clinician addressing him, did not make eye contact, was restless and occasionally displayed aggression and self-injurious behavior. These symptoms confirm the earlier diagnosis of Autism Spectrum Disorder (ASD). Therefore, the current study describes a case of co-occurrence of GLHS and ASD.
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PMID:Co-occurrence of Gomez-Lopez-Hernandez syndrome and Autism Spectrum Disorder: Case report with review of literature. 3018 40

We studied three patients with Unverricht-Lundborg disease for autistic features along with other clinical features associated with progressive myoclonus epilepsy. We diagnosed this disease based on noise and touch sensitive myoclonus, ataxia, cognitive decline, typical EEG features, normal MRI of the brain and applied Children's Global Assessment Scale and Childhood Autism Spectrum Test to these children. The CGAS score was 35 in two and 50 in one of them. CAST scores were above 15 in all of three of them. Autistic features may be an important clinical feature of this disease. History and physical examination for myoclonus should probably be taken in autistic children.
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PMID:Autistic features in Unverricht-Lundborg disease. 3146 70

Myosin Va (MyoVa) is a plus-end filamentous-actin motor protein that is highly and broadly expressed in the vertebrate body, including in the nervous system. In excitatory neurons MyoVa transports cargo toward the tip of the dendritic spine, where the post-synaptic density (PSD) is formed and maintained. MyoVa mutations in humans cause neurological dysfunction, intellectual disability, hypomelanation and death in infancy or childhood. Here we characterize the Flailer (Flr) mutant mouse, which is homozygous for a myo5a mutation that drives high levels of mutant MyoVa (Flr protein) specifically in the CNS. Flr protein functions as a dominant-negative MyoVa, sequestering cargo and blocking its transport to the PSD. Flr mice have early seizures and mild ataxia, but mature and breed normally. Flr mice display several abnormal behaviors known to be associated with brain regions that show high expression of Flr protein. Flr mice are defective in the transport of synaptic components to the PSD and in mGluR-dependent LTD and have a reduced number of mature dendritic spines. The synaptic and behavioral abnormalities of Flr mice result in an anxiety and memory deficits similar to that of other mouse mutants with Obsessive-compulsive disorder and Autism spectrum disorder (ASD). Because of the dominant-negative nature of the Flr protein, the Flr mouse offers a powerful system for the analysis of how the disruption of synaptic transport and lack of LTD can alter synaptic function, development and wiring of the brain and result in symptoms that characterize many neuropsychiatric disorders.SIGNIFICANCE STATEMENT Here we characterize a mutant mouse homozygous for a Myosin Va mutation named Flailer. The Flailer mutation generates a dominant-negative MyoVa transport motor protein that sequesters synaptic cargo and blocks synaptic transport, thereby resulting in an absence of LTD and in abnormal behaviors similar to those seen in anxiety and Autism Spectrum disorders. We propose that the Flailer mutant can be used as a model to study how the absence of LTD disrupts brain connectivity and behavior. Moreover, by using the Flailer mutation together with gene editing technologies it should be possible to target specific brain areas to remove the mutation and recover MyoVa function, thereby interrogating the role of a specific brain region in the control of a particular behavior.
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PMID:Myosin Va Brain-Specific Mutation Alters Mouse Behavior and Disrupts Hippocampal Synapses. 3322 12