Pyridoxine‐dependent and pyridoxine‐responsive seizures

Baxter, Peter

doi:10.1111/j.1469-8749.2001.tb00231.x

Cited by 39 publications

(60 citation statements)

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“…Clinical data were provided in a questionnaire. The currently applied classification of definite, probable, or possible PDE was performed as described [Baxter, 2001]. Definite PDE was stated if a formal pyridoxine withdrawal had resulted in reoccurrence of seizures that again responded to pyridoxine.…”

Section: Materials and Methods Patientsmentioning

confidence: 99%

“…Typically patients present with neonatal seizures, but atypical manifestations up to 3 years of age, as well as transient response to common anticonvulsants or poor initial response to pyridoxine have been reported [Gospe, 2002]. Until recently, a definite diagnosis of PDE had been established upon a successful therapeutic trial with pyridoxine and further proof of pyridoxine after a controlled withdrawal with recurrence of seizures [Baxter, 2001;Gospe, 1998Gospe, , 2002. Following the description of elevated pipecolic acid (PA) in plasma and cerebrospinal fluid (CSF) of patients with PDE [Plecko et al, 2000[Plecko et al, , 2005Willemsen et al, 2005], the underlying enzyme defect was shown to be located at the level of alpha-aminoadipic semialdehyde (AASA) dehydrogenase (antiquitin) in the cerebral lysine degradation pathway ( Fig.…”

Section: Introductionmentioning

confidence: 99%

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Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene

et al. 2006

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Section: Materials and Methods Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene

et al. 2006

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“…These diseases, except for most cases of TNSALP, are characterized by seizures, often beginning in the first days of life, not responsive to anticonvulsants and only controlled by vitamin B6 supplementation (Baxter 1999;Stockler et al 2011). Besides neonatal seizures, many patients suffer from developmental delay or intellectual disability, despite the seizure control (Baxter 2001;van Karnebeek et al 2016;Darin et al 2016;Walker et al 2000;Mills et al 2005Mills et al , 2014. Little is known about the specific biochemical changes that underlie the clinical symptoms of patients with vitamin B6 deficiency.…”

Section: Introductionmentioning

confidence: 99%

Vitamin B6 is essential for serine de novo biosynthesis

Ramos

Pras‐Raves

Gerrits

et al. 2017

J of Inher Metab Disea

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Pyridoxal 5′-phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug-resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6-deprived Neuro-2a cells. Significant alterations were observed in a range of metabolites. The most surprising observation was a decrease of serine and glycine, two amino acids that are known to be elevated in the plasma of vitamin B6 deficient patients. To investigate the cause of the low concentrations of serine and glycine, a metabolic flux analysis on serine biosynthesis was performed. The metabolic flux results showed that the de novo synthesis of serine was significantly reduced in vitamin B6-deprived cells. In addition, formation of glycine and 5-methyltetrahydrofolate was decreased. Thus, vitamin B6 is essential for serine de novo biosynthesis in neuronal cells, and serine de novo synthesis is critical to maintain intracellular serine and glycine. These findings suggest that serine and glycine concentrations in brain may be deficient in patients with vitamin B6 responsive epilepsy. The low intracellular 5-mTHF concentrations observed in vitro may explain the favourable but so far unexplained response of some patients with pyridoxine-dependent epilepsy to folinic acid supplementation.

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“…Reported dosages vary considerably, however, and current evidence for an optimum is limited (Haenggeli et al 1991;Baxter 2001;Nabbout et al 1999;Basura et al 2009). Specific recommendations on treatment with pyridoxine-HCl are beyond the scope of this paper.…”

Section: Pharmacotherapy: Recommendationmentioning

confidence: 99%