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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital enzymopathic hyperlactacidemia results from a defect of utilisation of pyruvate either at the level of the pyruvate junction (pyruvate-carboxylase, pyruvate-dehydrogenase and Kreb's cycle), or at the level of the unidirectional enzymes on neo-glucogenesis and of neo-glycogenogenesis, e.g. glucose-6-phosphatase, phosphoenol-pyruvate-carboxykinase and glycogen synthetase. The enzymopathies which affect neoglucogenesis associate hyper-lactacidemia and fasting hypoglycemia and more or less marked hepatomegaly. Type I glycogenesis (von Gierke's disease) is the best known example. Enzymopathies which affect the pyruvate junction and the Krebs cycle, may be manifested in addition by: --either chronic neuropathies, e.g. Leigh's disease, recurrent ataxia, and moderate hyperalactacidemia,--or, as in congenital lactic acidoses, which have a rapid and severe prognosis with major hyperlactacidemia. Functional investigation, in particular, loading tests are of great value in orientation and justify the practice of tissue biopsy which permits the enzyme diagnosis. Recent, still unconfirmed knowledge of the pathogenesis of these diseases emphasizes the considerable importance of estimation of blood lactic acid in the investigation of metabolic acidoses of hereditary origin.
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PMID:[Enzymopathic congenital hyperlactacidemia]. 18 25

A family--mother and 2 sons--with a heredodegenerative neurological disease is described. The disease started with bilateral optic atrophy, central scotoma, and color blindness during the second decade. This was followed by a quiescent period until additional neurological symptoms appeared, around the age of 50 years in the case of the mother and 40 and 30 years, respectively, in the sons. The additional symptoms were ataxia, spastic paresis, clonic jerks, grand mal seizures, psychia lability, and slight dementia. The disease was progressive, resulting in permanent hospitalization within a few years. The mother died at the age of 63 years and the sons at 46 and 43 years of age. Neuropathological examination revealed lesions histopathologically characteristic of subacute necrotizing encephalomyelopathy (SNE, Leigh disease), and their distribution in the brain and brainstem also conformed to this disease. On the basis of the clinical course and neuropathological findings, we consider that these 3 patients represent the first reported familial cases of the adult form of SNE.
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PMID:Familial subacute necrotizing encephalomyelopathy of the adult form (adult Leigh syndrome). 23 Jul 81

Subacute necrotizing encephalopathy (Leigh syndrome) is characterized by lactacidosis, seizures, ataxia, multiple cerebral hypervascularized lesions and mitochondrial oxidation defects. This is a report on a 21-year-old patient with proven Leigh syndrome, mild central and provokable peripheral lactacidosis, an extra-erythrocyte complex II defect, functionally reduced myokinase adenylate deaminase activity, but no ultrastructural mitochondrial changes. Determination of lactate, pyruvate and ammonia under ischemic conditions plus a pyruvate loading test were particularly useful. Oral flunarizine (Sibelium 30 mg/d) proved to be therapeutically effective.
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PMID:Diagnosis and treatment in a case of juvenile subacute necrotizing encephalopathy Leigh without cytochrome c oxidase deficiency. 132 78

A female infant showing lacticacidemia, hypotonia, and neurodegenerative disease died at 7 mo of age. Autopsy revealed lesions typical of Leigh disease, both in the basal ganglia and in the brain stem. A maternal aunt and uncle died 1 year and 5 mo, respectively, after following a similar clinical course, while another uncle, presently 33 years of age, has retinitis pigmentosa and ataxia and is mentally retarded. PCR restriction-digest analysis of mtDNA isolated from the proband revealed a T-to-G change at position 8993, creating a new AvaI restriction site. The mutation present in the ATP 6 gene results in the substitution of an arginine residue for a leucine. The indexed patient had greater than 95% abnormal mtDNA in her skin fibroblasts, brain, kidney, and liver tissues, as measured by laser densitometry. The maternal aunt who died at age 1 year had greater than 95% abnormal mtDNA in her lymphoblasts. The uncle with retinitis pigmentosa had 78% and 79% abnormal mtDNA in his skin fibroblasts and lymphoblasts, respectively, while an asymptomatic maternal aunt and her son had no trace of this mutation. The mother of the index case had 71% and 39% abnormal mtDNA in her skin fibroblasts and lymphoblasts, respectively, showing that the heteroplasmy can be variable, on a tissue-specific basis, within one individual. This shows that mtDNA mutations at 8993 can produce the clinical phenotype of Leigh disease in addition to the phenotype of ataxia and retinitis pigmentosa described by Holt et al.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heteroplasmic mtDNA mutation (T----G) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high. 830 53

Congenital oculomotor apraxia (COMA) was initially defined by Cogan in 1952. In this condition voluntary horizontal saccades cannot be generated, while slow horizontal pursuit movements and vertical eye movements are intact. Affected infants usually present with delayed visual and/or psychomotor development or may even appear to be blind. In the second half of the first year "compensatory" head thrust movements become apparent. While the oculomotor abnormalities tend to improve with increasing age most affected children have delayed motor and speech development. The cognitive development is commonly impaired and many children require a special scholastic education. In our personal series of 9 children we have found variable and nonspecific neuroradiological findings, including cerebellar hypoplasia, hypoplasia of corpus callosum and grey matter heterotopias. COMA has to be differentiated from acquired forms of ocular apraxia as seen in Morbus Gaucher type 3, ataxia teleangiectasia and Morbus Leigh.
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PMID:[Congenital oculomotor apraxia. Presentation--developmental problems--differential diagnosis]. 161 74

The purpose of the study was differential diagnosis of lactic acidosis in 44 children aged from 2 weeks to 4 years. In all of them the lactate level in repeated determinations exceeded 27 mg/100 ml. From the point of view of clinical manifestations the children were divided into three groups: 26 with hepatomegaly and hypoglycaemia (I), 6 with ataxia and retardation of somatic development (II), 12 with mental retardation and muscular hypotonia (III). Together with basic biochemical studies other tests were done, if necessary, including glucose and alanine loading, lactate determination in cerebrospinal fluid, analysis of urinary organic acids by the GC-MS method, morphological examinations of muscle biopsy material, enzymatic determinations in liver biopsy material. In group I glycogenosis was suspected and its type was finally established after biochemical and enzymatic tests (types I, Ib, III, VI, VIa, XI). In one case fructose-1,6-diphosphatase deficiency was suspected. In group II the clinical manifestations resembled Leigh's syndrome. The tests demonstrated an inhibition of glucose formation from alanine, and lactate level in the cerebrospinal fluid was evidently raised above that in the serum. Gasometric index showed the presence of respiratory alkalosis with metabolic compensation rather than primary lactate acidosis. In group III, with considerable clinical variety of signs, in only nine out of 12 children the cause of lactate acidosis could have been established (pathological changes of mitochondria in 4 cases, secondary increase of lactate without pathogenetic importance in 4, and 3-hydroxy-3-methylglutaric acidosis in 1 case. In conclusion it is thought that this combination of diagnostic methods is useful in differential diagnosis of congenital lactate acidosis in children.
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PMID:Congenital lactic acidosis in children--differential diagnosis in 44 cases. 184 18

Leigh's disease is one of the mitochondrial encephalomyopathies. This article presents a 7-month-old baby boy who had been well-being since birth until 6 months of age when episodic downward gaze of both eyes with limitation of horizontal eye movement were noted. This episode of cranial nerve palsies lasted about 4-5 days and subsided spontaneously. The second attack was noted one month later, to be associated with hypotonia and truncal ataxia. Episodic hyperventilation with resultant gasping and myoclonus was noted at the third attack but spontaneous respiration resumed soon with persistent ophthalmoplegia and truncal ataxia. Lumbar puncture, brain MRI, amino acid assay and cardiac echo all showed negative finding. The oral glucose lactate stimulation test revealed an elevation of lactic acid, brain stem evoked potential indicated bilateral obscure 4th and 5th waves, and muscle biopsy showed ragged red fibres with aggregation of structurally abnormal mitochondria noted under electron microscope. Coenzyme Q, thiamine and carnitine had been given before biochemical study; however, the neurological symptoms did not show any improvement. Biochemical study finally revealed normal respiratory chain enzymes including NADH-coenzyme Q reductase, succinate coenzyme Q reductase and cytochrome c oxidase while other enzymes were technically unavailable for study. Unfortunately the patient died at 18-month-old due to respiratory failure.
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PMID:Mitochondrial encephalomyopathy presenting with clinical Leigh's disease: report of a case. 184 64

Disturbances of pyruvate metabolism have been implicated in the aetiology of several neurological disorders including Leigh's disease and familial ataxia. We have re-investigated a patient whose initial description documented intermittent ataxia, a presumed disorder of pyruvate metabolism and an X-linked pattern of inheritance. Recent studies showed he had slow oxidation of pyruvate, low pyruvate dehydrogenase complex (PDC) activity and immunochemical evidence of E1 deficiency in skeletal muscle mitochondria. This is consistent with the recent finding that the gene for E1 alpha is on the X chromosome.
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PMID:Familial intermittent ataxia due to a defect of the E1 component of pyruvate dehydrogenase complex. 259 88

"Energy metabolism" is deranged in a wide variety of disorders of the nervous system. This term refers rather loosely to the pathways responsible for the utilization of the major substrates of brain. Primary disorders of energy metabolism are those in which the primary insult affects the cellular machinery required for energy metabolism. A typical example would be a defect in a gene coding for a mitochondrial protein. Biochemically, defects which appear to be hereditary and which lead to disease of the central nervous system have been described in each of the pathways of energy metabolism: glycogenolysis (the break-down of glycogen to glucose); glycolysis (the break down of glucose to pyruvate and lactate); the pyruvate dehydrogenase complex (which oxidizes pyruvate to enter the Krebs tricarboxylic acid cycle); the tricarboxylic acid cycle itself (which completes the oxidation of carbohydrates and other substrates to carbon dioxide); electron transport (which carries out their oxidation to water); the pentose phosphate pathway (an alternate pathway for glucose oxidation); and several "minor" mitochondrial pathways. Clinically, the spectrum of syndromes associated with primary disorders of energy metabolism is wide. Common manifestations include psychomotor retardation, with associated lactic acidosis and/or hypoglycemia. The laboratory abnormalities may be intermittent. Syndromes which have been culled out include congenital lactic acidosis, Leigh disease, intermittent ataxia, Kearns-Sayre-Shy syndrome (KSS), myoclonus epilepsy with ragged red fibers (MERRF), and mitochondrial myopathy-encephalopathy-lactic acidosis-stroke (MELAS). As with other families of inborn errors, both clinical and biochemical heterogeneity occur. Patients with apparently similar clinical syndromes can turn out to have different inborn errors, and patients with abnormalities of the same gene product can have clinically distinguishable syndromes. Secondary disorders are those in which the derangements of energy metabolism are presumably secondary to some other insult but may still be important for the cellular pathophysiology. These include the metabolic encephalopathies and probably a number of well-known neurodegenerative disorders. In the hereditary ataxias, abnormalities of mitochondrial markers are common but do not correlate consistently with the disorders as conventionally classified; a new classification into axonal ataxias, multiple system degenerations, and ataxic encephalopathies may be easier to relate to the pathophysiology.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Energy metabolism in disorders of the nervous system. 297 43

Leigh's encephalomyelopathy has been mainly observed in infancy and childhood. A later onset, during adolescence or adulthood has been rarely reported. Our patient was a 35 year-old man who died after 10 months of evolution of a subacute neurological syndrome, beginning with behavioural changes then a confusional state, epileptic fits, ataxia, autonomic disorders, abnormal alimentary behaviour and dementia. Diagnosis was only obtained by neuropathology, as in most of the published reports. However this diagnosis is suggested when exists an acute or subacute neurological pattern, beginning with visual defects and alimentary and social impairment, followed by a brain-stem syndrome. CT and M.R.I. will make it more easy. An earlier diagnosis could perhaps allow to discover the suspected enzymopathy responsible for Leigh's encephalomyelopathy and make clearer the relationship between Leigh's disease and encephalopathies with abnormal mitochondria.
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PMID:[An adult case of Leigh's subacute necrotizing encephalomyelopathy]. 304 33


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