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Disorders of vitamin B6 metabolism
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Patients present usually in the first days of life with seizures [15–17] (Table 100.1). Late onset disease has been observed [16]. Seizures may be tonic, clonic, or myoclonic, and may lead to apnea. Twitching eye movements have also been described [13]. Convulsions at birth have been described [17], and even in utero [17]. Birth is often complicated and one third of children present with asphyxia. Abnormal Apgar scores and cord blood gases may also be observed, and it is not uncommon for these newborns to be diagnosed hypoxic ischemic encephalopathy. Presentation with status epilepticus is common. Death in status epilepticus has been reported [17]. Seizures are typically unresponsive to the usual anticonvulsant medications, but some have had a good initial response to first line anti-epileptic drugs such as phenobarbitone or phenytoin [18]. Patients may be irritable or restless, and vomiting may occur. Other non-convulsive symptoms indicate that pyridoxine dependent epilepsy is an encephalopathy with epilepsy as the most dominant symptom.
Neonatal pyridoxine administration long lastingly accelerates cortical spreading depression in male rats, without affecting anxiety-like behavior
Published in Nutritional Neuroscience, 2021
Kelly Rayanne Gondim-Silva, Joselma M. da-Silva, Laís A. V. de Souza, Rubem C. A. Guedes
However, little is known about the brain effects of excessive pyridoxine; in animals, behavioral alterations, denoted by expressive vocalization, aggressiveness against another rat of the same cage and behavior of postural instability have been reported under conditions of excessive pyridoxine administration [9]. The amount of the pyridoxine present in the body is essential for the balance between the states of excitation and neuronal inhibition. Pyridoxine deficiency causes significant effects on different electrophysiological variables [4]. In brain excitability-related diseases, pyridoxine supplementation has been used in the treatment of infant seizures, to reduce seizures in neonatal epileptic encephalopathy, in isoniazid-induced epilepsy and ALDH7A1 mutation or pyridoxine-dependent epilepsy. These conditions do not respond to conventional anticonvulsant therapy, and the treatment consists of pyridoxine monotherapy, the main cofactor for the enzymatic conversion of the neurotransmitter glutamate to GABA [11,12]. Therefore, the development of experimental models to study the pyridoxine/brain excitability relationship is highly desirable.
Personalized treatment in the epilepsies: challenges and opportunities
Published in Expert Review of Precision Medicine and Drug Development, 2018
Simona Balestrini, Sanjay M Sisodiya
Pyridoxine (vitamin B6)-dependent epilepsy is caused by biallelic mutations in the ALDH7A1 gene, which encodes antiquitin. Deficiency of antiquitin causes seizures because accumulating 1-piperideine-6-carboxylate condenses with pyridoxal 5′-phosphate (PLP) and inactivates this latter enzyme cofactor essential for normal metabolism of neurotransmitters. ALDH7A1 analysis could also be used for prenatal diagnosis of pyridoxine-dependent epilepsy. Seizures are often fully controlled by treatment with pyridoxine [44]. B6-responsive seizures may also be due to mutations in the pyridox(am)ine 5′-phosphate oxidase (PNPO) gene, and in some cases may be better treated with PLP [45]. A lysine-restricted diet, the aim of which is to restrict formation of potentially toxic intermediate metabolites, has been recently proposed as an adjunctive treatment in cases where response to pyridoxine is incomplete, although the evidence for benefit remains limited [46,47].
Advances in genetic testing and optimization of clinical management in children and adults with epilepsy
Published in Expert Review of Neurotherapeutics, 2020
Marcello Scala, Amedeo Bianchi, Francesca Bisulli, Antonietta Coppola, Maurizio Elia, Marina Trivisano, Dario Pruna, Tommaso Pippucci, Laura Canafoglia, Simona Lattanzi, Silvana Franceschetti, Carlo Nobile, Antonio Gambardella, Roberto Michelucci, Federico Zara, Pasquale Striano
Pyridoxine-dependent epilepsy (PDE) is caused by mutations in PNPO, encoding an enzyme catalyzing the biosynthesis of pyridoxal-5ʹ-phosphate (PLP) [138]. This is the active form of pyridoxine and is necessary for several biological processes, including neurotransmitter biosynthesis. PDE is characterized by convulsive seizures with onset right after birth, or even before. AEDs are generally not effective, but these patients respond well to high daily doses of PLP. More recently, DEPDC5 mutations have been associated with sporadic and familial epilepsy types with a broad phenotypic spectrum [139].