Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A simple fluorescent spot screening test has been developed for the identification of individuals with arginase deficiency (hyperargininemia). The assay is based on the coversion of arginine to ornithine and urea by arginase present in 1/8 inch disc of dried blood on filter paper. The enzyme activity is visually estimated by the oxidation of NAD-H to NAD+ in a coupled kinetic reaction. In the absence of the enzyme, there is no oxidation of the NAD-H and consequently no loss of fluorescence. The screening assay has been used to identify successfully both heterozygous and homozygous arginase-deficient crabeater macaques (M. fascicularis) as well as three patients with hyperargininemia. This test can be used to screen large numbers of patients with mental retardation or seizure disorders rapidly to determine the frequency of this disorder more precisely.
 ...
PMID:A simple screening test for arginase deficiency (hyperargininemia). 84 87

Seven L-amino acids (Trp, Arg, Lys, Met, Ile, Val, and Phe) partially (28-81%) reversed the inhibitory action of 1 microM gamma-aminobutyric acid (GABA) on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to rat brain membranes, with EC50 values ranging from 5 to 120 mM. D-Trp, D-Arg, D-Lys, D-Met, D-Val, and D-Phe were approximately equipotent with their L-isomers. Tyramine, phenethylamine, and tryptamine, the decarboxylation products of the aromatic amino acids (Tyr, Phe, and Trp, respectively), reversed the inhibitory action of 1 microM GABA on [35S]TBPS binding more potently than the parent amino acids (EC50 values = 1.5-3.0 mM). Human hereditary amino acidemias involving Arg, Lys, Ile, Val, and Phe are associated with seizures, and these amino acids and/or their metabolites may block GABA-A receptors. Five other L-amino acids (ornithine, His, Glu, Pro, and Ala) as well as Gly and beta-Ala inhibited [35S]TBPS binding with IC50 values ranging from 0.1 to 37 mM, and these inhibitions were reversed by the GABA-A receptor blocker R 5135 in all cases. The inhibitory effects of L-ornithine, L-Ala, L-Glu, and L-Pro were stereospecific, because the corresponding D-isomers were considerably less inhibitory. L-His, D-His, and L-Glu gave incomplete (plateau) inhibitions. Human hereditary amino acidemias involving L-ornithine, His, Pro, Gly, and beta-Ala are also associated with seizures, and we speculate that these GABA-mimetic amino acids may desensitize GABA-A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Two groups of amino acids interact with GABA-A receptors coupled to t-[35S]butylbicyclophosphorothionate binding sites: possible involvement with seizures associated with hereditary amino acidemias. 284 55

Two siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria are reported. The clinical picture included protein intolerance, mental retardation, seizures, and stuporous episodes. One patient had cerebellar ataxia, myoclonus, convulsive seizure, and muscular weakness in both legs. Isolated liver mitochondria in the patient revealed that ornithine transport and citrulline synthesis were decreased, but urea cycle enzymes and ornithine aminotransferase were normal. Ornithine metabolism was decreased in cultured skin fibroblasts.
 ...
PMID:Hyperornithinemia, hyperammonemia, and homocitrullinuria: case report and biochemical study. 367 Jun 19

A patient with the hyperornithinemia, hyperammonemia, homocitrullinuria syndrome is described. This patient represents the 12th documented case of this rare, presumably autosomal recessive condition. Increased levels of ammonia, ornithine and homocitrulline were demonstrated in blood and cerebrospinal fluid. The blood ammonia concentration could be lowered by supplementation of the diet with low doses of arginine. High doses of arginine precipitated seizures, although plasma levels of arginine and ornithine were not altered. The uptake of ornithine by the particulate fraction of the patient's fibroblasts was lower than that of controls, but still measurable. It is suggested that HHH patients have a partial impairment of the uptake of ornithine by mitochondria.
 ...
PMID:Studies on a case of HHH-syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria). 396 Feb 84

Evidence of genetic factors in seizure disorders by examination of plasma amino acid concentrations in multiply affected sibships was investigated. The strategy of multiply affected sibship ascertainment was used to reduce heterogeneity as one of several potential sources of variation in quantitative amino acid levels. Our results do not support previously reported increases in plasma taurine, aspartic acid, or glutamic acid in seizure patients. However, we do find that multiply affected sibships have significantly elevated plasma concentrations of arginine and asparagine, and significantly decreased ornithine. These amino acid concentrations may be under quantitative genetic control. Within-sibship comparisons indicate that seizure patients have increased glutamine and decreased lysine and phenylalanine, possibly secondary to the seizures. We also find that anticonvulsant use complicates statistical analyses. Further studies to more clearly delineate the genetics of plasma amino acid concentrations (or other quantitative metabolic measures) and their role in seizure disorders are required and will benefit from the use of a homogeneous sampling strategy.
 ...
PMID:Altered amino acid levels in multiply affected sibships with seizures. 407 67

Free amino acid patterns of cerebrospinal fluid in infants and children with various types of convulsive disorders were compared with those in age-matched normal subjects. The total free amino levels in Lennox syndrome were higher than the normal values, and those in infantile spasms controlled by ACTH were higher than those in uncontrolled infantile spasms. Although the levels of only one or two amino acids in tonic-clonic seizure, focal seizure and febrile seizure were higher or lower than those of the controls, the levels of 8 amino acids in infantile spasms were lower and those of 10 amino acids in Lennox syndrome were generally higher compared to the controls. Among amino acids in CSF of children with tonic-clonic seizure, infantile spasms or Lennox syndrome, only the ornithine level was commonly lower than that of the controls. After the treatment, in tonic-clonic seizure, the levels of taurine, asparagine and glycine were increased, and in infantile spasms, those of asparagine, glutamine, glycine, alanine, phenylalanine, lysine and arginine were increased while that of taurine was decreased. These results suggest that each type of convulsive disorder shows the specific amino acid pattern, and the effects of anticonvulsants may be partially understood through the changes of the free amino acid patterns in the brain.
 ...
PMID:Amino acid metabolism in the brain with convulsive disorders. Part 3: Free amino acid patterns in cerebrospinal fluid in infants and children with convulsive disorders. 632 17

Shortly after birth, a newborn girl developed anorexia, hypotonia, apneic attacks and seizures. After 61 h the child died in coma. Biochemically, a highly elevated blood ammonia level was found together with an increased plasma level of the amino acids mainly involved in ammonia detoxication. Enzyme studies in post-mortem liver tissue material revealed a deficiency of carbamoyl-phosphate synthetase (0.9% of the mean value in controls) in combination with an intermediate activity of L-ornithine: 2-oxoglutarate aminotransferase (40% of the mean value in controls).
 ...
PMID:A lethal neonatal variant of carbamoyl-phosphate synthetase deficiency in combination with an intermediate activity of L-ornithine: 2-oxoglutarate amino-transferase. 685 Dec 28

Central pontine myelinolysis (CPM) is a demyelinating condition of the central pons with or without associated foci of demyelination in extrapontine areas. We present a case of partial ornithine carbamoyl transferase deficiency in a 5-year-old girl which was complicated by CPM. The patient was a previously undiagnosed girl who presented with mild hyperammonemic encephalopathy with a maximum plasma ammonia level of 376 microM on admission. Laboratory testing established the diagnosis of OCT deficiency, and therapy with hydration and protein restriction was successful in returning the plasma ammonia levels to normal. Five days after correction of her hyperammonemia, the patient developed intractable seizures and coma. Serial MRI scans of the brain revealed the evolution of the characteristic findings of CPM. Plasma ammonia and electrolyte concentrations were well controlled throughout this time. This represents the first description of CPM in a patient with a urea cycle defect.
 ...
PMID:Central pontine myelinolysis as a complication of partial ornithine carbamoyl transferase deficiency. 757 73

Pretreatment of mice with 5-fluoromethylornithine (5FMOrn), a selective inactivator of ornithine aminotransferase, diminishes the accumulation of ammonia in the brain after administration of ammonium acetate, and antagonizes ammonia-induced fatal tonic extensor convulsions. In about 50% of the treated animals the loss of the righting reflex and coma is prevented. Presumably these effects are based on the enhancement of urea formation by the increased liver ornithine concentrations. However, since brain ornithine concentrations are greatly enhanced by 5FMOrn, it is not excluded that ornithine has direct effects on cellular events involved in ammonia-induced seizure generation, even though 5FMOrn had no anticonvulsant properties in a series of established animal seizure models, including N-methyl-D,L-aspartate-induced convulsions. NMDA receptor antagonists are capable of preventing death, but do not protect against the generation of coma and tonic extensor convulsions in ammonium acetate intoxicated mice. Since no evidence was found for ammonia-induced glutamate release from rat hippocampus, there is no convincing evidence for the idea that the tonic convulsions are mediated by NMDA receptors. L-Methionine-D, L-sulfoximine (MSO)-induced seizures can be partially antagonized by pretreatment with 5FMOrn. However, the effect is considerably smaller than against ammonia-induced convulsions, although at the time of seizure onset brain ammonia levels of MSO-intoxicated mice were lower than in the animals receiving ammonium acetate. This suggests that MSO-convulsions are not entirely due to the elevation of brain ammonia concentrations, even though MSO administration mimics effects of ammonia on cortical inhibitory neuronal interactions.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Enhanced endogenous ornithine concentrations protect against tonic seizures and coma in acute ammonia intoxication. 809 10

We have studied the role of putrescine by using transgenic mouse lines overexpressing the human ornithine decarboxylase gene in most of their tissues. The aberrant expression of the transgene is most strikingly manifested in the brain, leading to an increase of up to 20-fold in putrescine content. We report that the transgenic mice with grossly elevated putrescine in all brain regions analysed (cortex, striatum, hippocampus and cerebellum) showed a significantly elevated seizure threshold to chemical and electrical stimuli, and impaired performance in spatial learning and memory tests. The view that putrescine may be primarily responsible for these changes was supported by the fact that the concentrations of the major neurotransmitter amino acids, glutamate and GABA in the brain, were not changed in the transgenic animals, and by the finding that a further increase in brain putrescine, achieved by inhibition of the catabolism of L-ornithine, appeared to provide additional protection against electroshock-induced seizures. These results suggest that the commonly observed increase in ornithine decarboxylase activity and the massive increase in brain putrescine in connection with neuron damage is a neuroprotective measure rather than a cause of the damage.
 ...
PMID:Elevated seizure threshold and impaired spatial learning in transgenic mice with putrescine overproduction in the brain. 828 26


1 2 3 Next >>