Pyridoxine-dependent epilepsy

A hereditary combination of various seizure types that occur in neonates and are unresponsive to standard ANTICONVULSANT AGENTS. They can be treated only by the immediate administration of PYRIDOXINE HYDROCHLORIDE. This treatment must continue or the seizures will re-appear. Some patients show developmental delay. Prevalence is 1 in 400,000 to 700,000 births. Germline mutations in the ALDH7A1 gene have been identified. OMIM: 266100

Also Known As:

Networked: 180 relevant articles (2 outcomes, 6 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Seizures (Absence Seizure)
2.	Homocystinuria
3.	Brain Diseases (Brain Disorder)
4.	Epilepsy (Aura)
5.	succinic semialdehyde dehydrogenase deficiency

Experts

1.	Gospe, Sidney M: 15 articles (01/2022 - 03/2002)
2.	Jakobs, Cornelis: 15 articles (12/2013 - 10/2005)
3.	Mercimek-Mahmutoglu, Saadet: 11 articles (01/2016 - 05/2009)
4.	van Karnebeek, Clara D M: 10 articles (01/2022 - 11/2012)
5.	Struys, Eduard: 10 articles (01/2016 - 03/2006)
6.	Bok, Levinus A: 9 articles (01/2022 - 08/2007)
7.	Coughlin, Curtis R: 9 articles (01/2022 - 11/2012)
8.	Struys, Eduard A: 9 articles (01/2021 - 08/2007)
9.	Clayton, Peter T: 8 articles (01/2021 - 03/2006)
10.	Hyland, Keith: 8 articles (01/2021 - 05/2009)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Pyridoxine-dependent epilepsy:

1.	Pyridoxine (Pyridoxin)FDA LinkGeneric 05/01/2021 - "Several reports suggest that administration of high doses of pyridoxine can be helpful in improving disturbances such as anxiety and pyridoxine-dependent epilepsy, although it has also been associated with a proconvulsive action. " 07/01/2015 - "Case Report: Intravenous and Oral Pyridoxine Trial for Diagnosis of Pyridoxine-Dependent Epilepsy." 09/01/1996 - "Pyridoxine-dependent epilepsy: the need for repeated pyridoxine trials and the risk of severe electrocerebral suppression with intravenous pyridoxine infusion." 10/31/2023 - "Pearls & Oy-sters: Delayed Response to Pyridoxine in Pyridoxine-Dependent Epilepsy." 01/01/2020 - "Patients with pyridoxine-dependent epilepsy may respond well to low-dose pyridoxine. "
2.	Lysine (L-Lysine)FDA Link 11/01/2012 - "Lysine restricted diet for pyridoxine-dependent epilepsy: first evidence and future trials." 03/01/2023 - "Pyridoxine-dependent epilepsy (PDE) (OMIM 266100) is an autosomal recessive disorder of lysine metabolism secondary to antiquitin deficiency. " 08/25/2022 - "Lysine Reduction and Cognitive Outcomes in Pyridoxine-Dependent Epilepsy: A New Approach to an Old Disease." 11/25/2020 - "Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disease caused by mutations in the ALDH7A1 gene leading to blockade of the lysine catabolism pathway. " 09/01/2020 - "The lysine degradation pathway is clinically relevant due to the occurrence of two severe neurometabolic disorders, pyridoxine-dependent epilepsy (PDE) and glutaric aciduria type 1 (GA1). "
3.	Arginine (L-Arginine)FDA Link 01/01/2016 - "Effect of dietary lysine restriction and arginine supplementation in two patients with pyridoxine-dependent epilepsy." 01/01/2016 - "A Prospective Case Study of the Safety and Efficacy of Lysine-Restricted Diet and Arginine Supplementation Therapy in a Patient With Pyridoxine-Dependent Epilepsy Caused by Mutations in ALDH7A1." 11/01/2014 - "Novel therapy for pyridoxine dependent epilepsy due to ALDH7A1 genetic defect: L-arginine supplementation alternative to lysine-restricted diet." 01/01/2022 - "An Atypical Presentation of Pyridoxine-Dependent Epilepsy Diagnosed with Whole Exome Sequencing and Treated with Lysine Restriction and Supplementation with Arginine and Pyridoxine." 12/01/2021 - "Clinical and biochemical outcome of a patient with pyridoxine-dependent epilepsy treated by triple therapy (pyridoxine supplementation, lysine-restricted diet, and arginine supplementation)."
4.	Oxidoreductases (Dehydrogenase)IBA 06/01/2022 - "Little is known about pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency (PDE-ALDH7A1) in adulthood, as the genetic basis of the disorder has only been elucidated 15 years ago. " 12/31/2021 - "Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive neurometabolic disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase (mutation in ALDH7A1 gene), more commonly known as antiquitin (ATQ). " 01/01/2021 - "Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency." 04/01/2014 - "Pyridoxine dependent epilepsy (PDE) is caused by mutations in the ALDH7A1 gene encoding α-aminoadipic semialdehyde dehydrogenase. " 12/01/2008 - "Pyridoxine-dependent seizures caused by alpha amino adipic semialdehyde dehydrogenase deficiency: the first polish case with confirmed biochemical and molecular pathology."
5.	allysineIBA 12/01/2008 - "The diagnosis of pyridoxine-dependent seizures was confirmed with biochemical and molecular testing revealing elevated alpha-AASA excretion and the presence of 2 different mutations in the antiquitin ( ALDH7A1) gene. " 08/01/2007 - "Pyridoxine-dependent seizures in Dutch patients: diagnosis by elevated urinary alpha-aminoadipic semialdehyde levels." 07/01/2010 - "This study aimed to evaluate the use of measurement of urine L-alpha-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. " 01/01/2014 - "This paper describes a full detailed high performance liquid chromatography/tandem mass spectrometry method for the identification and quantification of human urine alpha-aminoadipic semialdehyde, biomarker of pyridoxine-dependent epilepsy. " 01/01/2010 - "Pyridoxine-dependent seizures are due to deficiency of alpha-aminoadipic semialdehyde dehydrogenase (antiquitin) which is encoded by ALDH7A1. "
6.	Vitamin B 6IBA 07/01/2012 - "Pyridoxine dependent epilepsy (PDE) is characterized by neonatal epileptic encepahalopathy responsive to pharmacological doses of vitamin B6. " 10/01/2021 - "Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive developmental and epileptic encephalopathy that is responsive to pharmacologic doses of vitamin B6. " 01/01/2017 - "This results in the pathogenic accumulation of the lysine intermediates Aminoadipate Semialdehyde (AASA) and its cyclic equilibrium form Piperideine-6-carboxylate (P6C) in body fluids; P6C reacts with pyridoxal-5'-phosphate (PLP, the active form of vitamin B6) causing its inactivation and leading to pyridoxine-dependent seizures. " 02/01/1995 - "An 18-year-old man was treated from birth with chronic high dose pyridoxine (vitamin B6) up to 2000 mg per day for pyridoxine-dependent seizures. " 01/01/2017 - "Pyridoxine-dependent epilepsy (PDE) is a rare genetic condition characterized by intractable and recurrent neonatal seizures that are uniquely alleviated by high doses of pyridoxine (vitamin B6). "
7.	Neurotransmitter Agents (Neurotransmitter)IBA 04/01/2016 - "Severely affected infants sometimes also have hypercalcaemia and hyperphosphataemia due to the blocked entry of minerals into the skeleton, and pyridoxine-dependent seizures from insufficient extracellular hydrolysis of pyridoxal 5'-phosphate, the major circulating form of vitamin B6, required for neurotransmitter synthesis. " 09/01/1994 - "To assess the role of glutamate as an excitatory neurotransmitter and neurotoxin in pyridoxine-dependent epilepsy. " 04/01/2011 - "Cerebrospinal fluid neurotransmitter metabolite chromatography and an assay of serum biomarkers, including pipecolic acid and α-aminoadipic semialdehyde, confirmed the diagnosis of pyridoxine-dependent epilepsy, and genetic testing identified a homozygous mutation in our patient, and in a first cousin with epilepsy. " 02/08/2015 - "Twenty out of the 150 patients (13.3%) were diagnosed with a genetic disorder including inherited neurotransmitter disorders (6 patients) (dihydropteridine reductase, 6-pyruvoyl-tetrahydropterin synthase, guanosine triphosphate cyclohydrolase I, tyrosine hydroxylase, pyridoxine dependent epilepsy due to mutations in the ALDH7A1 gene and pyridoxamine-5-phosphate oxidase deficiencies) and non-neurotransmitter disorders (14 patients). " 01/01/2020 - "Examples are drawn from Komrower's description of treatment of homocystinuria and the author's trials of treatment in bile acid synthesis disorders (3β-hydroxy-Δ5 -C27 -steroid dehydrogenase deficiency and Δ4 -3-oxosteroid 5β-reductase deficiency), neurotransmitter amine disorders (aromatic L-amino acid decarboxylase [AADC] and tyrosine hydroxylase deficiencies), and vitamin B6 disorders (pyridox(am)ine phosphate oxidase deficiency and pyridoxine-dependent epilepsy [ALDH7A1 deficiency]). "
8.	Phosphates (Orthophosphate)IBA 08/01/2009 - "Two are caused by reduced synthesis/availability of PLP (Pyridox(am)in-phosphate oxidase (PNPO) deficiency and infantile hypophosphatasia) and two by increased utilization/inactivation (pyridoxine-dependent epilepsy and hyperprolinemia type II). " 02/08/2015 - "Twenty out of the 150 patients (13.3%) were diagnosed with a genetic disorder including inherited neurotransmitter disorders (6 patients) (dihydropteridine reductase, 6-pyruvoyl-tetrahydropterin synthase, guanosine triphosphate cyclohydrolase I, tyrosine hydroxylase, pyridoxine dependent epilepsy due to mutations in the ALDH7A1 gene and pyridoxamine-5-phosphate oxidase deficiencies) and non-neurotransmitter disorders (14 patients). " 01/01/2020 - "Examples are drawn from Komrower's description of treatment of homocystinuria and the author's trials of treatment in bile acid synthesis disorders (3β-hydroxy-Δ5 -C27 -steroid dehydrogenase deficiency and Δ4 -3-oxosteroid 5β-reductase deficiency), neurotransmitter amine disorders (aromatic L-amino acid decarboxylase [AADC] and tyrosine hydroxylase deficiencies), and vitamin B6 disorders (pyridox(am)ine phosphate oxidase deficiency and pyridoxine-dependent epilepsy [ALDH7A1 deficiency]). "
9.	Tyrosine 3-Monooxygenase (Tyrosine Hydroxylase)IBA 02/08/2015 - "Twenty out of the 150 patients (13.3%) were diagnosed with a genetic disorder including inherited neurotransmitter disorders (6 patients) (dihydropteridine reductase, 6-pyruvoyl-tetrahydropterin synthase, guanosine triphosphate cyclohydrolase I, tyrosine hydroxylase, pyridoxine dependent epilepsy due to mutations in the ALDH7A1 gene and pyridoxamine-5-phosphate oxidase deficiencies) and non-neurotransmitter disorders (14 patients). " 01/01/2020 - "Examples are drawn from Komrower's description of treatment of homocystinuria and the author's trials of treatment in bile acid synthesis disorders (3β-hydroxy-Δ5 -C27 -steroid dehydrogenase deficiency and Δ4 -3-oxosteroid 5β-reductase deficiency), neurotransmitter amine disorders (aromatic L-amino acid decarboxylase [AADC] and tyrosine hydroxylase deficiencies), and vitamin B6 disorders (pyridox(am)ine phosphate oxidase deficiency and pyridoxine-dependent epilepsy [ALDH7A1 deficiency]). "
10.	SteroidsIBA 01/01/2020 - "Examples are drawn from Komrower's description of treatment of homocystinuria and the author's trials of treatment in bile acid synthesis disorders (3β-hydroxy-Δ5 -C27 -steroid dehydrogenase deficiency and Δ4 -3-oxosteroid 5β-reductase deficiency), neurotransmitter amine disorders (aromatic L-amino acid decarboxylase [AADC] and tyrosine hydroxylase deficiencies), and vitamin B6 disorders (pyridox(am)ine phosphate oxidase deficiency and pyridoxine-dependent epilepsy [ALDH7A1 deficiency]). "

Therapies and Procedures

1.	Therapeutics 01/01/2022 - "Timing of therapy and neurodevelopmental outcomes in 18 families with pyridoxine-dependent epilepsy." 06/01/2005 - "In addition, pyridoxine-dependent seizures are discussed as an example of an etiology of refractory seizures that responds well to replacement therapy." 08/25/2022 - "Association Between Lysine Reduction Therapies and Cognitive Outcomes in Patients With Pyridoxine-Dependent Epilepsy." 01/01/2014 - "Lysine-Restricted Diet as Adjunct Therapy for Pyridoxine-Dependent Epilepsy: The PDE Consortium Consensus Recommendations." 12/01/2010 - "Pyridoxine-dependent epilepsy (PDE) is characterized by therapy-resistant seizures (TRS) responding to intravenous (IV) pyridoxine. "
2.	Ketogenic Diet 10/15/2019 - "There was a direct treatment implication in 6% of patients with inherited metabolic disorders including pyridoxine dependent epilepsy, glucose transporter 1 deficiency and neuronal ceroid lipofuscinosis type 2. Additionally, there might be some treatment implications in 30% of patients with genetic diagnoses including SCN1A, SCN2A, SCN8A, and KCNQ2 associated epilepsies by application of effective anti-epileptic drugs or the ketogenic diet therapy. "
3.	Injections 01/01/2023 - "Additionally, we measure the IR spectra of two closely eluting diastereomeric biomarkers for the inborn error of metabolism pyridoxine-dependent epilepsy (PDE-ALDH7A1), which shows that the heartcutting LC-IRIS setup has good sensitivity (requiring ∼μL injections of ∼μM samples) and that the separation between closely eluting isomers is maintained. "
4.	Aftercare (After-Treatment) 07/01/2013 - "To describe a case of pyridoxine-dependent epilepsy and developmental status after treatment. "