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 patient of pyridoxine dependent seizures was reported. He was born at 34 weeks' gestation and weighted 2,760 g. Apgar scores were 6 and 9 at 1 and 5 minutes, respectively. He showed the first seizure 2 hours after his birth. Phenobarbital, phenytoin, sodium valproate, diazepam and clonazepam were not effective. Pyridoxal phosphate (50 mg) was given intravenously, resulting in suppression of convulsions. However, muscle tonus was severely depressed. In EEG, a discontinuous pattern was found in quiet and indeterminate sleep on the 2nd day of life. At 5th week multifocal spikes were found, and the discontinuous pattern persisted. Ictal discharges at 13th week showed generalized, continuous, irregular and high voltage slow waves with multifocal spikes. At 27th week of life, high voltage slow waves disappeared and multifocal spike discharges decreased. At 2 years and 10 months of age, the patient was suffering from athetotic cerebral palsy and severe mental retardation. Pyridoxal phosphate at the doses of 35-40 mg/kg/day had been administered. Irritability sometimes occurred and additional 50 mg of pyridoxal phosphate controlled this irritability effectively.
 ...
PMID:[Chronological change of EEG findings in a case of pyridoxine dependency seizures]. 222 90

Pyridoxal phosphate and its synthetic analogues--pyridoxal 5'-sulphate and the 5-phosphonoethyl analogue of pyridoxal (phosphonoethyl pyridoxal) in doses of 0.125-0.250 (mumol/10 microliters/i.c.v./rat), caused epileptic seizures characterized by running fits, vocalization, muscular fasciculation and tonic-clonic convulsions. These effects were specific and could not be demonstrated with 5'-deoxypyridoxal, N-methylpyridoxal phosphate or the 5-trans-carboxyethenyl analogue of pyridoxal phosphate (carboxyethenyl pyridoxal). Structure-activity relationships of these analogues indicated that the presence of a CHO in position 4 of the pyridine ring was essential, since its conversion to CH2NH2 or CH2OH abolished activity. The presence of an unsubstituted N was essential, since convulsions did not occur with N-methylpyridoxal phosphate. The presence of the hydroxyl group in position 5' was essential since 5'-deoxypyridoxal was inactive. The convulsive activity was potentiated in the presence of both CHO and PO4, CHO and CH2--CH2PO2-4 but especially CHO and --OSO23-- groups. This seizure activity was prevented, attenuated or reversed by intracerebroventricular administration of 20 microliter of GABA (1 mumol), muscimol (0.025 mumol), trans-4-aminocrotonic acid (0.25 mumol), isoguvacine (0.25 mumol) or THIP (0.25 mumol), but not by biogenic amines. An understanding of the mechanism of pyridoxal phosphate-related seizures may provide additional insights not only about GABA receptor sites but also about the biochemical manifestation and expression of epilepsy.
 ...
PMID:Convulsant activity of pyridoxal sulphate and phosphonoethyl pyridoxal: antagonism by GABA and its synthetic analogues. 662 16

We investigated the etiology of West syndrome (WS) with special reference to prenatal factors in 180 cases. Prenatal cause was the most frequent diagnosis (77 cases, 42.8%), followed by perinatal (25 cases, 13.9%) and postnatal factors (12 cases, 6.7%); 48 cases (26.7%) were of uncertain etiology; eighteen cases (10.0%) were idiopathic. Of the three forms of age-dependent epileptic encephalopathy, prenatal cause was present in 12 of 15 cases (80.0%) of early-infantile epileptic encephalopathy with suppression-burst, 77 of 180 cases (42.8%) of WS, and 31 of 123 cases (25.2%) of Lennox-Gastaut syndrome (LGS). Prenatal factors of WS included tuberous sclerosis (23), chromosome abnormalities (10), cerebral dysgenesis (10), porencephaly (7), hydrocephalus (5), Aicardi syndrome (3), Aicardi syndrome associated with chromosome abnormality (1), and other causes (18). Chromosome abnormalities with WS consisted of 6 cases with 21 trisomy and one case each with 18q duplication, t(1;y) translocation, 7q duplication, and partial 2p trisomy. One patient with Aicardi syndrome also had a t(12;21) translocation. No significant difference was observed in the age of onset of WS among the five etiologic groups. The evolution from WS to LGS was not influenced by etiology, except for the idiopathic group. In patients followed for over 3 years, seizure remission occurred in 46.8% (22 of 47 cases) of the prenatal group. This was lower than the other four groups. Intellectual prognosis was also relatively poor in those with prenatal onset. Pyridoxal phosphate (PAL-P) treatment was effective in 9 of 70 (12.9%) prenatal cases and 5 of 18 (27.8%) idiopathic cases.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prenatal etiologies of West syndrome. 833 May 83

Pyridox(am)ine-5'-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5'-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unresponsive to pyridoxine.
 ...
PMID:Pyridoxal phosphate-dependent neonatal epileptic encephalopathy. 1829 73

Pyridoxal phosphate and pyridoxamine phosphate, the catalytically active forms of vitamin B(6), influence brain function by participating at stages in metabolism of proteins, lipids, carbohydrates, other coenzymes and hormones. Vitamin B(6) participates in the metabolism of amino acids in the form of decarboxylation, transamination, deamination, racemization and desulfhydration reactions. The crucial roles that these coenzymes play in the maintenance of functional integrity of the brain become evident when one realizes that some compounds implicated as neurotransmitters are synthesized and/or metabolized by the aid of the vitamin B(6)-dependent enzymatic reactions. These include dopamine, norepinephrine and serotonin, tyramine, tryptamine, taurine, histamine, gamma aminobutyric acid, and even acetylcholine indirectly. In recent years, the above-mentioned biogenic amines have become of considerable interest to neurobiologists who are investigating the etiology and the pathological manifestations of many disorders of the central nervous system such as Parkinsonism, Huntington's chorea, minimal brain disfunction, schizophrenia, depression, sleep disorders and seizure disorders. Vitamin B(6) deficiency in these cases is characterized by anemia, growth retardation and alteration in neuronal function, including neuropathies, hyperirritability, hyperexcitability and convulsions. The importance of vitamin B(6) in the study of brain function assumes still greater significance when one considers the effects of nutritional deficiencies on growth and development of the brain and mental processes and in the involvement of vitamin B(6) in some inborn errors of metabolism which result in mental retardation. Vitamin B(6) deficiency results in a lowered concentration of Coenzyme A in blood, in reduced absorption and storage of vitamin B(12), and in increased excretion of vitamin C. Furthermore, vitamin B(6) acts synergistically with vitamin E to control metabolism of unsaturated fats, with vitamin C in tyrosine metabolism and with niacin in its action and participates in niacin synthesis. In addition, vitamin B(6) deficiency results in insufficiency of insulin and in alteration of the functions of adrenal and pituitary glands, since it is involved in the synthesis of growth hormone, follicle-stimulating hormone, luteinizing hormone, aldosterone, glucagon, cortisol, estradiol, testosterone and epinephrine. It is hoped that by understanding the factors that regulate the synthesis, binding, storage and degradation of pyridoxal phosphate in the brain, a better insight into the role of vitamin B(6) in neurobiology may be gained.
 ...
PMID:Regulation and function of pyridoxal phosphate in CNS. 1964 63

The treatment of neonatal seizures generally relies on the use of one or more anticonvulsant medications along with evaluation and management of any underlying etiology. In some circumstances, neonatal seizures are refractory to therapy and result in poor outcomes, including death. Certain rare vitamin- responsive inborn errors of metabolism may present as neonatal encephalopathy with anticonvulsant-resistant seizures. Therefore, it is vital for the clinicians of caring for seizing encephalopathic newborns to consider these particular disorders early in the hospital course. Pyridoxine-dependent seizures are due to deficiency of alpha-aminoadipic semialdehyde dehydrogenase (antiquitin) which is encoded by ALDH7A1. Seizures in infants who are pyridoxine-dependent must be treated using pharmacologic doses of pyridoxine (vitamin B(6)), and life-long therapy is required. Despite medical therapy, developmental handicaps, particularly in expressive language, are common. Folinic acidresponsive seizures are treated with supplements of folinic acid (5-formyltetrahydrofolate). Recently, patients with this condition were also demonstrated to be antiquitin deficient. Pyridoxal phosphate-dependent seizures result from a deficiency of pyridox(am)ine 5'-phosphate oxidase which is encoded by PNPO. Patients with this cause of seizures respond to pyridoxal phosphate but not to pyridoxine. This review discusses our current understanding of these three neonatal vitamin-responsive epileptic encephalopathies and a diagnostic and treatment protocol is proposed.
 ...
PMID:Neonatal vitamin-responsive epileptic encephalopathies. 2018 90

Pyridox(am)ine-5'-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5'-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unresponsive to pyridoxine.
 ...
PMID:Pyridoxal phosphate-dependent neonatal epileptic encephalopathy. 2168 93

An infant carrying a heterozygous c.43_46delACTA and a heterozygous c.668 G>A mutation in the ALPL gene with hypophosphatasia in the absence of bone deformities presented with therapy-resistant seizures. Pyridoxal phosphate was extremely high in CSF and plasma. Pyridoxine treatment had only a transient effect and the severe encephalopathy was fatal. Repeated brain MRIs showed progressive cerebral damage. The precise metabolic cause of the seizures remains unknown and pyridoxine treatment apparently does not cure the epilepsy.
...
PMID:Infantile hypophosphatasia without bone deformities presenting with severe pyridoxine-resistant seizures. 2410 Feb 44

Pyridoxal phosphate (PLP) is the active form of vitamin B6 and a cofactor in many enzyme reactions including neurotransmitter metabolism. PLP metabolism disturbances may mostly lead to refractory seizures. In this report, we review the main pathophysiological factors related with PLP deficiency and our experience in PLP treatment in pediatric patients with low-normal cerebrospinal fluid PLP values who presented epilepsy. Only one case had a definite diagnosis (Phelan-McDermid syndrome). The results of extensive metabolic workups and targeted genetic studies were normal for all patients. In 5 cases, the response to PLP supplementation (10-30mg/kg/d) was initially positive. PLP adverse reactions were noticed in 4 patients and PLP was discontinued; however, one of the most noticeable symptoms was an asymptomatic increase in liver enzymes. These negative results with PLP supplementation are worth reporting, to improve the information we use to treat our patients.
 ...
PMID:Pyridoxal Phosphate Supplementation in Neuropediatric Disorders. 2828 96