Disturbance of GABA Metabolism in Pyridoxine-Dependent Seizures

Kurlemann, Gerhard; Ziegler, Ralph; Grüneberg, Marianne; Bömelburg, T.; Ullrich, Karl Julius; Palm, D.

doi:10.1055/s-2008-1071353

Cited by 32 publications

(17 citation statements)

References 7 publications

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“…conversion to GABA is impaired [Lott et al, 1978;Kurlemann et al, 1992;Baumeister et al, 1994]. Similar demonstrations of low GABA concentrations in the brain and cerebrospinal fluid (CSF) during states of pyridoxine-deficiency [Coursin, 1954] as well as during states of pyridoxyl phosphate inhibition [Gospe, 1998], e.g.…”

Section: Pyridoxine-dependent Seizures-the Disordermentioning

confidence: 88%

Disorders of glutamate metabolism

Kelly

Stanley

2001

Ment. Retard. Dev. Disabil. Res. Rev.

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The significant role the amino acid glutamate assumes in a number of fundamental metabolic pathways is becoming better understood. As a central junction for interchange of amino nitrogen, glutamate facilitates both amino acid synthesis and degradation. In the liver, glutamate is the terminus for release of ammonia from amino acids, and the intrahepatic concentration of glutamate modulates the rate of ammonia detoxification into urea. In pancreatic beta-cells, oxidation of glutamate mediates amino acid-stimulated insulin secretion. In the central nervous system, glutamate serves as an excitatory neurotransmittor. Glutamate is also the precursor of the inhibitory neurotransmittor GABA, as well as glutamine, a potential mediator of hyperammonemic neurotoxicity. The recent identification of a novel form of congenital hyperinsulinism associated with asymptomatic hyperammonemia assigns glutamate oxidation by glutamate dehydrogenase a more important role than previously recognized in beta-cell insulin secretion and hepatic and CNS ammonia detoxification. Disruptions of glutamate metabolism have been implicated in other clinical disorders, such as pyridoxine-dependent seizures, confirming the importance of intact glutamate metabolism. This article will review glutamate metabolism and clinical disorders associated with disrupted glutamate metabolism.

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Section: Pyridoxine-dependent Seizures-the Disordermentioning

confidence: 88%

Disorders of glutamate metabolism

Kelly

Stanley

2001

Ment. Retard. Dev. Disabil. Res. Rev.

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“…These disorders include pyridoxine-dependent epilepsies, GABA-transaminase deficiency and succinic-semialdehyde-dehydrogenase deficiency (Battaglioli et al, 2000;Gibson et al, 1998;MedinaKauwe et al, 1999). Subjects with pyridoxine-dependent epilepsies have been observed to have extremely low CSF GABA levels, elevated glutamate, and low levels of brain GABA (Kurlemann et al, 1992;Kure et al, 1998;Battaglioli et al, 2000). Recent reports have suggested that similar changes in CSF GABA occur in children with infantile spasms (Ohtsuka et al, 2000).…”

Section: Part Ii: Mrs Studies Of the Role Of Gaba In Epilepsymentioning

confidence: 97%

MRS Studies of the Role of Altered Glutamate and GABA Neurotransmitter Metabolism in the Pathophysiology of Epilepsy

Petroff

Spencer

2004

Brain Energetics and Neuronal Activity

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“…However, recent evidence has thrown doubt on this theory and molecular diagnosis is still not available (Battaglioli et al 2000). Thus, the observation of recurrent seizures after pyridoxine withdrawal has been the only available way of establishing a definitive diagnosis of pyridoxine dependency (Kurlemann et al 1992, Baumeister et al 1994, Gospe 1998. A non-intentional trial was carried out in this case when the vitamin complex containing pyridoxine, given as supplementation, was withdrawn at 70 days of age.…”

Section: Discussionmentioning

confidence: 99%

“…It has been thought that a defect in glutamate decarboxylase apoenzyme binding of its cofactor pyridoxal phosphate could be the underlying molecular defect in pyridoxine-dependent seizures (Lott et al 1978, Kurlemann et al 1992, Baumeister et al 1994, Gospe et al 1994, Gospe 1998). However, recent evidence has thrown doubt on this theory and molecular diagnosis is still not available (Battaglioli et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Pyridoxine‐dependent seizures responding to extremely low‐dose pyridoxine

Grillo

Silva

Barbato

2001

Develop Med Child Neuro

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We report on a male infant with pyridoxine dependency and seizures from birth, controlled with pharmacological doses of pyridoxine at 4 months of age. Seizures stopped between 30 and 80 days of age when very‐low doses of pyridoxine were given in a multivitamin supplement. Daily dose was 0.5 mg that corresponded to 0.08 to 0.16 mg/kg/day when weight gain is considered. In previous reports doses have ranged from 0.2 to 30 mg/kg/day. Another distinctive feature was that this infant went into a coma and developed hypotonia and irregular breathing when pyridoxine was given by enteral tube which has usually been reported when the vitamin is given intravenously. Use of low doses of pyridoxine in multivitamin supplements could be a confounding factor for early diagnosis and appropriate treatment of pyridoxine‐dependent seizures.

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Disturbance of GABA Metabolism in Pyridoxine-Dependent Seizures

Cited by 32 publications

References 7 publications

Disorders of glutamate metabolism

Disorders of glutamate metabolism

MRS Studies of the Role of Altered Glutamate and GABA Neurotransmitter Metabolism in the Pathophysiology of Epilepsy

Pyridoxine‐dependent seizures responding to extremely low‐dose pyridoxine

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