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

The case of a mentally retarded girl with a number of dysmorphic features, Raynaud's phenomenon, hypotonia and petit mal seizures is presented. Laboratory investigations showed alpha-aminoadipic aciduria and a high level of fetal haemoglobin. Oral L-lysine loading resulted in a marked increase of alpha-aminoadipic acid in blood and urine. After 3 months of pyridoxine medication the increase of alpha-aminoadipic acid in blood and urine during the oral L-lysine loading test was less than in the test before treatment. A normal degradation rate of DL-alpha-amino [1-14C] adipic acid in fibroblasts of the patient, as measured by 14CO2 production, did not indicate a primary enzyme defect in the alpha-aminoadipic acid transamination or decarboxylation steps. The persistent HbF could be the result of stress on the erythropoiesis by a secondary induced defect in an early stage of haemoglobin synthesis in which alpha-amino-beta-ketoadipic acid, a structural analogue of alpha-amino-adipic acid, is an intermediate.
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PMID:alpha-Aminoadipic aciduria and persistence of fetal haemoglobin in an oligophrenic child. 616 32

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.
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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

The effects of centrally injected prostaglandins (PGE1 and PGF2 alpha), arachidonic acid and lysine acetylsalicylate were examined on the seizure activity and temperature changes produced by pentylentetrazole (PTZ) and also on maximal electroshock (MES) seizures. PGE1 antagonised both PTZ and MES seizures whilst PGF2 alpha had the reverse effect. In addition both PGs alone produced hyperthermia but attenuated PTZ hypothermia. Arachidonic acid protected against PTZ--but potentiated MES--seizures whilst lysine acetylsalicylate augmented the effects of both convulsive stimuli. Lysine acetylsalicylate and arachidonic acid alone were transiently hyperthermic and also antagonised PTZ hypothermia though the total net effect may have been due to a functional antagonism. It is suggested from these findings that PGE1 has anticonvulsant effects whilst PGF2 alpha promotes seizures neither of these properties correlating with thermoregulatory actions.
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PMID:Modification of convulsive behaviour and body temperature in mice by intracerebroventricular administration of prostaglandins, arachidonic acid and the soluble acetylsalicylic acid salt lysine acetylsalicylate. 679 2

Late-onset multiple carboxylase deficiency is characterized clinically by skin rash, alopecia, seizures and ataxia and occasionally by candidiasis and developmental delay. Biochemically, these individuals exhibit findings consistent with a combined deficiency of the biotin-dependent carboxylases. We have found that the activity of the enzyme biotinidase is also deficient in the sera of five affected children (0 to 3% of mean control activity, 5.80 +/- 0.89 nmol X min-1 X ml-1 serum), and believe that it represents the primary biochemical defect in this disease. Biotinidase catalyzes the removal of biotin from the epsilon-amino group of lysine, through which biotin is covalently bound to the four known human carboxylases, thereby regenerating biotin for reutilization. The deficient activity in our patients was not due to an inhibitor, particularly biotin. It is also not a consequence of feedback control in affected individuals under treatment with pharmacologic doses of biotin. The biotinidase activities of the parents of those children who were available for study were intermediate between deficient and normal values (46% to 65% of mean normal activity). Children lacking biotinidase activity are unable to recycle biotin, and are thus entirely dependent upon exogenous biotin to prevent deficiency. Our findings indicate that the primary biochemical defect in late-onset multiple carboxylase deficiency is in biotinidase activity which is inherited as an autosomal recessive trait.
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PMID:Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. 688 21

alpha-Aminoadipic acid (alpha AA) is an intermediate in lysine metabolism. We report a new case with alpha AA excess in urine and plasma, without alpha-ketoadipic acid, in a full-term male child born to unrelated parents; he presented at 24h of life with seizures that failed to respond to phenobarbital, clonazepam, and Vigabatrin and death occurred on the 38th day of life. Brain imaging suggested antenatal haemorrhage. Small quantities of alpha AA were also detected in the blood and urine of both parents and a healthy brother, all three of whom exhibited the same defect in platelet aggregation as the deceased child. Both parents had decreased levels of plasma neopterin, a finding that might be related to the immunodeficiency described in other cases.
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PMID:Abnormal alpha-aminoadipic acid excretion in a newborn with a defect in platelet aggregation and antenatal cerebral haemorrhage. 762 43

The function of the N-methyl-D-aspartate (NMDA)-preferring glutamate receptor can be regulated by extracellular pH, a process that may be important during ischemia in the brain or during seizures. Protons inhibit NMDA receptor function by 50 percent at pH 7.3 through interactions with the NR1 subunit, and both polyamines and NR1 exon 5 potentiate receptor function through relief of the tonic proton inhibition present at physiological pH. A single amino acid (lysine 211) was identified that mediates the effects of exon 5 in the rat brain. Electroneutral substitutions at this position restored pH sensitivity and, consequently, polyamine relief of tonic inhibition. This effect, together with the structural similarities between polyamines and the surface loop encoded by exon 5, suggest that exon 5 may act as a tethered pH-sensitive constitutive modulator of NMDA receptor function.
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PMID:Control of proton sensitivity of the NMDA receptor by RNA splicing and polyamines. 775 71

We report myoclonic epilepsy with ragged-red fibers (MERRF) syndrome in a Chinese family with confirmed mitochondrial DNA point mutation. Six members of the family including the grandmother, two siblings, and three grandchildren were affected. Among them, action myoclonus was seen in five; short stature, muscle weakness, and mental retardation in four; lactic acidosis, hearing impairment, and ataxia in two; and seizures in one. Muscle biopsy from two affected siblings revealed ragged-red fibers and abundant subsarcolemmal mitochondria with paracrystalline inclusions. Pedigree analysis suggests a maternal transmission. Analysis of mitochondrial DNA showed a point mutation from A to G at the 8344th nucleotide position located in the tRNA(Lys) gene. To our knowledge, this is the first report of MERRF syndrome with such genetic defect from a Chinese family. The present and previous reports support the notion that mitochondrial DNA point mutation at the 8344th nucleotide position is the most common cause of MERRF syndrome.
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PMID:Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome: report of a Chinese family with mitochondrial DNA point mutation in tRNA(Lys) gene. 793 36

L-Lysine 10 mmol/kg given to mice for 1 to 10 days significantly increased clonic and tonic seizure latencies caused by 60 mg/kg pentylenetetrazol (PTZ). On day 1 the clonic and tonic seizure latencies were increased from 160.4 +/- 26.3 and 828.6 +/- 230.8 s to 286.1 +/- 103.3 and 982.3 +/- 98.6 s, respectively. Both clonic and tonic seizure latencies increased steadily with additional L-lysine treatment without significant change in survival rate. On day 10, the anticonvulsant effect reached its highest level with a block of tonic seizures and a survival rate of 100% without tolerance developing. Acute L-lysine treatment significantly increased the mean clonic latency from 85.8 +/- 5.24 to 128.2 +/- 9.0 s and the mean tonic seizure latency from 287.2 +/- 58.7 to 313.5 +/- 42.2 s with 80 mg/kg PTZ. On the day 10 of treatment, the anticonvulsant effect of L-lysine was highest, with a significant increase of 155 and 184% in clonic and tonic latencies over the control, respectively. After 15- and 20-day treatment, clonic and tonic seizures latencies and survival rate decreased, suggesting development of tolerance. Brain membranes from tolerant mice showed decreased enhancement by gamma-aminobutyric acid of specific [3H]flunitrazepam binding from 210 +/- 8 to 169 +/- 5% with EC50 values of 4.1 +/- 1.4 and 7.8 +/- 1.5 microM, respectively. Scatchard analysis of [3H] flunitrazepam binding showed no significant change of apparent binding affinity (KD) or binding density (Bmax) after chronic L-lysine exposure. L-Lysine enhanced the specific [35S]tert-butyl bicyclophosphorothionate (TBPS) binding in brain membranes dose dependently.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic L-lysine develops anti-pentylenetetrazol tolerance and reduces synaptic GABAergic sensitivity. 838 23

Amino acid levels in plasma were measured by amino acid autoanalyser in 130 convulsive children. The levels of taurine, serine and tryptophan were significantly lower in convulsive children as compared to normal control; in contrast, isoleucine, homocystine, GABA, histidine, arginine and ammonia were higher. The children with paroxysmal disorders (headache, dizziness and abdominal epilepsy) had the highest levels of isoleucine, histidine and arginine and the lowest levels of glutamate and cystein. Clinical seizure activity within 6 months prior to the test seemed to have no obvious effect on the plasma amino acid pattern, except for the levels of glycine and arginine tended to return to normal, and the level of GABA was significantly increased in patients with the seizure being controlled. The patients treated with carbamazepin as a single anticonvulsant had the highest GABA level compared to those with other anticonvulsants. Hyperglycinemia and hyperammonaemia were also noted in patients who took valproic acid. The levels of serine, isoleucine and phenylalanine in the CSF within 6 hours after convulsion were significantly lower than the normal control; while asparagine, tyrosine, lysine and arginine were significantly higher. The concentration of ammonia in the CSF was also elevated after convulsion as compared to the normal control. Amino acids play an important role in the generation of epilepsy and recently there has been an increasing number of studies to help determine their effects during an epileptic attack. However, there still is much debate and controversy on this topic. Therefore, further studies are needed and researchers should carefully consider factors that might affect the accurate assessment of the results.
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PMID:Alteration of amino acid in plasma and cerebrospinal fluid of children with seizure disorders. 851 Jan 96

The mitochondrial DNA (mtDNA) transfer RNA (tRNA)Lys A-->G(8344) mutation was identified in seven patients. These patients and their relatives were assessed clinically; in one family the mutation was deduced to be present in four generations. The phenotype in index cases was consistent with the syndrome of myoclonic epilepsy with ragged red fibres, with the core clinical features of myoclonus, ataxia and seizures. Amongst other features, progressive external ophthalmoplegia, Leigh's syndrome and stroke-like episodes were observed, well recognized in mitochondrial myopathies but novel manifestations of this genotype. Samples of blood and muscle were analysed for the proportion of mutant mtDNA using an oligonucleotide hybridization technique. The proportion of mutant mtDNA in blood was significantly greater in symptomatic than asymptomatic cases. Furthermore, the proportion of mutant mtDNA in blood correlated with age of onset of disease and clinical severity assessed by a simple scale. Study of disease associated with the tRNA(Lys) A-->G(8344) mutation provides further insight into the pathogenesis and transmission of mitochondrial diseases. Quantification of the proportion of mtDNA in tissues demonstrates that this is a major factor determining the course of disease, but other, as yet unidentified factors are also likely to play a role.
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PMID:The mitochondrial DNA transfer RNA(Lys)A-->G(8344) mutation and the syndrome of myoclonic epilepsy with ragged red fibres (MERRF). Relationship of clinical phenotype to proportion of mutant mitochondrial DNA. 851 95


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