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 clinical phenotype of multiple acyl-CoA dehydrogenase deficiency in infancy is characterized by recurrent episodes of hypoketotic hypoglycemia and lipid storage myopathy. Brain damage has been described only as a consequence of severe and protracted hypoglycemia. We describe a child who experienced normal physical and psychomotor development until the age of 3 years, who then developed progressive intention tremors, dysarthria, ataxia, and spastic tetraparesis. Episodes of acute metabolic distress were never observed. Magnetic resonance imaging disclosed abnormal signals within the white matter of the brain and cerebellum, suggesting leukodystrophy. Gas chromatography/mass spectrometry analysis revealed abnormally high levels of glutaric acid, dicarboxylic acids, and glycine derivatives in urine. Riboflavin therapy was initiated at 4 years of age, when the patient had already lost control of trunk and head posture. Consistent improvement rapidly occurred after riboflavin supplementation. Glutaric aciduria type II may cause brain damage, in spite of the absence of acute metabolic distress, and should be considered in the differential diagnosis of leukodystrophies.
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PMID:Riboflavin-responsive glutaric aciduria type II presenting as a leukodystrophy. 877 Nov 70

We report a right-handed 22-year-old man with muscle atrophy. His prenatal course and the delivery were uneventful, but he walked unsupported at 15 months of the age for the first time. He was apparently well but he was in the slowest group in running in schools. He noted a difficulty in climbing up stairs at 19 years of the age, and he was admitted to our hospital for the work up when he was 22-year-old. His family history and past medical history were unremarkable. On admission, he was a slender and tall guy in no acute distress. General physical examination was unremarkable, but he had high-arched palate and high-arched feet. On neurologic examination, mental status and higher cerebral functions were normal. Cranial nerves appeared intact, however, he had a thin and long face without weakness. The sternocleidomastoid muscles appeared somewhat atrophic and were moderately weak. He was able to walk normally, however, he needed a handrail when he went up stairs. Thigh muscles and triceps surae muscles were atrophic and slightly weak (4/ 5). Muscle tone was hypotonic and no deep tendon reflexes were elicited except for jaw jerk. No ataxia or involuntary movements were seen; sensation was intact. Laboratory examination was unremarkable except for slight increase in serum CK to 145 IU/L. An ischemic forearm exercise test revealed slight elevation of lactate and pyruvate in that base line levels were 5.4 mg/dl and 0.52 mg/dl, respectively, which rose to 11.4 mg/dl and 0.85 mg/dl, respectively, 20 minutes after the initiation of the ischemic exercise. The base line serum ammonia was 102.5 micrograms/dl which decreased to 64.8 micrograms/dl at 20 minutes. A diagnostic biopsy was performed from the left quadriceps femoris muscle. The patient was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had nemaline myopathy. Opinions were divided between nemaline myopathy and debranching enzyme deficiency. The results of the ischemic exercise was not typical of glycogen storage disease, but elevations of lactate and pyruvate did not appear to be sufficient to be interpreted as normal. Histologic examination of the biopsied specimen revealed marked type I fiber predominance and abundant nemaline rods. Cytoplasmic bodies were also seen. Histologic characteristics were consistent with the diagnosis of nemaline myopathy. The possibility of concomitant presence of AMP deaminase deficiency was discussed, because serum ammonia did not elevate in the ischemic exercise test.
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PMID:[A 22-year-old man with long-standing weakness and atrophy predominantly in the lower extremities]. 879 13

A total of 42 birds from a flock of 104 farmed ostriches showed signs of toxicity after the accidental inclusion of monensin in their concentrate ration. The initial clinical signs were muscle weakness and ataxia which progressed to recumbency, dyspnoea and death, despite intensive supportive therapy. The serum activity of the enzymes creatine kinase, aspartate aminotransferase and lactate dehydrogenase was high in the affected birds, indicating significant muscle pathology. Few gross lesions were identifiable postmortem, but widespread lesions of degenerative myopathy were present at the histopathological level. However, these degenerative changes were restricted to the skeletal muscle and there was no evidence of cardiomyopathy in any of the birds examined. The birds were fed a ration which contained 215 to 224 ppm monensin for 13 days. New clinical cases ceased to occur shortly after the withdrawal of the source of monensin, but all the individuals which showed clinical signs of toxicity died or were euthanased on humane grounds.
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PMID:Monensin toxicity in a flock of ostriches. 922 93

We describe a patient who presented with progressive ataxia, seizures, mental deterioration, mild myopathy, and hearing loss. A novel heteroplasmic G-to-A transition was found, affecting the acceptor stem of the mitochondrial (mt) tRNA(Val) gene. Mutant mtDNA was 67% of total mtDNA in the muscle of the proband and was also present at low levels in the muscle of his healthy mother. It was absent in all of the numerous control DNA samples that were tested. Analysis of single muscle fibers revealed a significantly greater level of mutant mtDNA in cytochrome c oxidase-negative fibers. Mutations of mtDNA may be responsible of neurological syndromes that, like the case reported here, are clinically puzzling, and lack typical "mitochondrial" clues, such as elevated levels of blood lactate, overt defects of the respiratory complexes, and clinically documented maternal inheritance.
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PMID:A novel mutation in the mitochondrial tRNA(Val) gene associated with a complex neurological presentation. 945 Jul 73

A 65 year old woman, referred for differential diagnosis of dementia, presented with cognitive and mnestic deficits. Typical signs and symptoms of hypothyroidism led to the diagnosis of severe autoimmune thyroiditis. After six months of treatment with thyroid hormone, dementia, myopathy and ataxia had disappeared. The neurologic and neuropsychologic manifestations of hypothyroidism are discussed. In dementia the diagnosis of secondary and reversible forms is of great importance with regard to prognosis and treatment. Hypothyroidism is known to be a common and treatable cause of pseudodementia. Early diagnosis and adequate treatment are important to prevent further permanent deterioration of cerebral function.
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PMID:[Reversible dementia]. 965 92

The protozoan parasite Toxoplasma gondii is a serious cause of fetal mortality in sheep and goats. Oocysts, the parasite stage responsible for initiating infection, are produced following a primary infection in cats. A primary infection in pregnant sheep and goats can establish a placental and fetal infection which may result in fetal death and resorption, abortion or stillbirth. Diagnosis is aided by the clinical picture, the presence of characteristic small white necrotic foci in placental cotyledons, the possible presence of a mummified fetus and on fetal serology and histopathology. Development of the polymerase chain reaction (PCR) specific for T. gondii may also provide a valuable diagnostic tool. Measures to control abortion include improved management of farm cats, fodder and water. Vaccination of sheep with the live vaccine is an effective preventive measure and the use of decoquinate in feed may be useful in some situations. Neospora caninum is related to T. gondii and while its asexual life cycle is similar to that of the latter it is currently not known whether it has a similar sexual life cycle in a definitive host. Neospora is an important cause of fetal loss in cattle and parallels that of T. gondii infection in sheep and goats. While it does not appear to cause frequent losses in these latter animals, experimental infection is readily induced in them and if initiated during pregnancy provides a very good model of the bovine infection. Furthermore clinical signs and pathological lesions in sheep and goats are similar to those induced in them by T. gondii, although there are subtle histopathological differences. These changes will aid possible diagnosis as will specific serological tests such as the indirect immunofluorescent antibody test and the enzyme linked immunosorbent assay and the PCR. Sarcocystis, which exists as numerous species, undergoes a coccidian-like life cycle with each having a distinctive definitive (usually carnivore) host which excretes sporocysts into the environment. Clinical sarcocystiosis is much less commonly diagnosed than toxoplasmosis and neither is it normally associated with fetal infection or abortion in either sheep or goats. However, infection is extremely common throughout the world and follows ingestion of food or water contaminated with sporocysts. Clinical signs, when seen, include fever, anaemia, inappetance and weight loss or reduced weight gain. Central nervous signs (hind limb weakness, ataxia, paresis), acute myopathy and death may occur. Diagnosis is difficult as infection is so common and clinical signs absent, mild or non-specific. Serology may be useful in some situations and histopathology/immunohistochemistry is valuable for confirming the cause of death. Control relies on preventing contamination of pasture and water with faeces of dogs, foxes and cats or by controlling access of young susceptible stock to contaminated land. Relatively little is known of the immunity induced by infection with Sarcocystis spp. but research indicates that protective immunity does develop and that cell-mediated mechanisms are probably important. It is likely that sarcocystiosis is underdiagnosed as a problem and that better diagnostic methods are needed to show the true extent of the losses caused. Neosporosis on the other hand would appear not to be so common in sheep and goats. The value of experimental infections in these animals may be to provide a comparative model of the infection in cattle in the same way that our understanding of toxoplasmosis in sheep provides a superior model of human toxoplasmosis.
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PMID:Protozoan infections (Toxoplasma gondii, Neospora caninum and Sarcocystis spp.) in sheep and goats: recent advances. 968 43

We report seven unrelated families with mitochondrial tRNA(Ser(UCN)) gene mutations at three different loci. A novel G7497A mutation is found in two families, both of which present with progressive myopathy, ragged-red fibers, lactic acidosis, and deficiency of respiratory chain complexes I and IV. This mutation presumably affects the tertiary tRNA(Ser(UCN)) dihydrouridine interaction. Mutations 7472 insC and T7512C, found in three and two families, respectively, are associated with myoclonus epilepsy, deafness, ataxia, cognitive impairment, and complex IV deficiency. No ragged-red fibers or ultrastructural abnormalities are seen. It is interesting that 6 of our 7 index patients are apparently homoplasmic, indicating a minor pathogenetic power of the tRNA(Ser(UCN)) mutations.
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PMID:Progressive myoclonus epilepsy and mitochondrial myopathy associated with mutations in the tRNA(Ser(UCN)) gene. 977 62

Epilepsia partialis continua (EPC) is a rare epileptic syndrome characterized by continuous focal seizures. We report on a 16-year-old girl who died of prolonged pharmacoresistant EPC in whom we identified a 7472insC mutation within the mitochondrial transfer ribonucleic acid (tRNA)(ser(UCN)). Additional symptoms included ataxia, lactic acidosis, myopathy, sensorineural hearing loss, severe headaches, and mental retardation. Quantification revealed 100% mutant mitochondrial DNA (mtDNA) in the patient, 4% in her mother, and none in her half-sister. This highly skewed mtDNA distribution is most improbable (approximately 3 x 10(-30)) if only explained by random genetic drift. Clustering of dysfunctional mitochondria and replicatory advantage of mutant mtDNA may play a role in the rapid segregation towards homoplasmy within one generation.
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PMID:Epilepsia partialis continua associated with a homoplasmic mitochondrial tRNA(Ser(UCN)) mutation. 977 73

The A-to-G mutation at position 8344 in the transfer RNAlysine mitochondrial DNA gene is associated mostly with the myoclonic epilepsy and ragged red fibers syndrome. We describe a five-generation family with this mutation and 19 affected members with a variant neurologic syndrome of ataxia, myopathy, hearing loss, and neuropathy. Along with axial lipomas and diabetes mellitus, hypertension is a frequent somatic feature, suggesting that mitochondrial mutations may contribute to hypertension in these patients.
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PMID:Expanding the phenotype of the 8344 transfer RNAlysine mitochondrial DNA mutation. 981 78

A critical analysis of the changes in fatty acid patterns and their metabolism elicited by vitamin E deficiency leads to the proposal that a major role of dietary RRR-alpha-tocopherol (alpha-TOC) is as an enzymatic precursor of alpha-tocopherolquinone (alpha-TQ) whose semiquinone radical functions as an essential enzyme cofactor for the fatty acid desaturases of the recently elucidated carnitine-dependent, channeled, mitochondrial desaturation-elongation pathway; a detailed mechanism for its function is proposed. Pathophysiological states produced by vitamin E deficiency and alpha-TOC transfer protein defects, such as ataxia, myopathy, retinopathy, and sterility are proposed to develop from the effects of impaired alpha-TQ-dependent desaturases and the resulting deficiency of their polyenoic fatty acid products.
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PMID:A function for the vitamin E metabolite alpha-tocopherol quinone as an essential enzyme cofactor for the mitochondrial fatty acid desaturases. 1010 Jun 2


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