{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:46:10Z","timestamp":1784720770689,"version":"3.55.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:00:00Z","timestamp":1649721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> To analyze the clinical feature, treatment, and prognosis of epileptic spasms (ES) in vitamin B6\u2013dependent epilepsy, including patients with pyridoxine-dependent epilepsy (PDE) caused by <jats:italic>ALDH7A1<\/jats:italic> mutation, pyridox(am)ine-5\u2032-phosphate oxidase (<jats:italic>PNPO<\/jats:italic>) deficiency, and <jats:italic>PLPBP<\/jats:italic> deficiency.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We analyzed data from a cohort of 54 cases with PDE, 13 cases with <jats:italic>PNPO<\/jats:italic> deficiency, and 2 cases with <jats:italic>PLPBP<\/jats:italic> deficiency and looked for the presentation of ES among them.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A total of 11 patients with the seizure presentation of ES have been collected. Among them, four patients carried mutations in <jats:italic>ALDH7A1<\/jats:italic>, six carried mutations in <jats:italic>PNPO<\/jats:italic>, and the remaining one carried mutation in <jats:italic>PLPBP<\/jats:italic>. The analysis of this cohort identified nine cases presenting as infantile spasms distributed in the three diseases and two cases presenting as Ohtahara syndrome diagnosed with PDE and <jats:italic>PNPO<\/jats:italic> deficiency, respectively. In the PDE and <jats:italic>PLPBP<\/jats:italic> deficiency groups, seizures were controlled by pyridoxine monotherapy, and the remaining one had refractory seizures due to secondary brain atrophy. In the groups with <jats:italic>PNPO<\/jats:italic> deficiency, one patient showed seizure-free when treated by PLP combined with valproic acid, three still had infrequent seizures treated by PLP monotherapy or pyridoxine or PLP combined with other antiseizure medications, and two died. In two cases presenting as Ohtahara syndrome, after regular treatment, one showed seizure-free, the others showed a marked decrease in seizure frequency, and they both showed an improvement in EEG.<\/jats:p><jats:p><jats:bold>Significance:<\/jats:bold> ES might be a common form of seizures in <jats:italic>PNPO<\/jats:italic> deficiency, and EEG presented as hypsarrhythmia or a burst suppression pattern. It is difficult for pyridoxine to control frequent seizures caused by secondary brain injury. In our <jats:italic>PNPO<\/jats:italic> deficiency cohort, patients with infantile spasms did not respond better to PLP than pyridoxine. Timely and correct treatment could prevent the transformation of the child\u2019s disease from Ohtahara syndrome and infantile spasms to subsequent epileptic encephalopathy or refractory epilepsy.<\/jats:p>","DOI":"10.3389\/fgene.2022.804461","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T04:47:11Z","timestamp":1649738831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["A Rare Presentation Characterized by Epileptic Spasms in ALDH7A1, Pyridox(am)ine-5\u2032-Phosphate Oxidase, and PLPBP Deficiency"],"prefix":"10.3389","volume":"13","author":[{"given":"Xianru","family":"Jiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s11011-016-9933-8","article-title":"Phenotype, Biochemical Features, Genotype and Treatment Outcome of Pyridoxine-dependent Epilepsy","volume":"32","author":"Al Teneiji","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1111\/cge.13843","article-title":"Phenotypic and Molecular Spectrum of Pyridoxamine\u20105\u2032\u2010phosphate Oxidase Deficiency: A Scoping Review of 87 Cases of Pyridoxamine\u20105\u2032\u2010phosphate Oxidase Deficiency","volume":"99","author":"Alghamdi","year":"2021","journal-title":"Clin. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s00431-008-0823-x","article-title":"Clinical Features and the Management of Pyridoxine-dependent and Pyridoxine-Responsive Seizures: Review of 63 North American Cases Submitted to a Patient Registry","volume":"168","author":"Basura","year":"2009","journal-title":"Eur. J. Pediatr."},{"key":"B4","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.pediatrneurol.2012.06.002","article-title":"Early-onset Epileptic Encephalopathies: Ohtahara Syndrome and Early Myoclonic Encephalopathy","volume":"47","author":"Beal","year":"2012","journal-title":"Pediatr. Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1111\/j.1528-1167.2008.01816.x","article-title":"Prevalence ofALDH7A1mutations in 18 North American Pyridoxine-dependent Seizure (PDS) Patients","volume":"50","author":"Bennett","year":"2009","journal-title":"Epilepsia"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1016\/j.ajhg.2016.10.011","article-title":"Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B6-dependent Epilepsy","volume":"99","author":"Darin","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/epi.14679","article-title":"Efficacy and Tolerability of the Ketogenic Diet versus High-Dose Adrenocorticotropic Hormone for Infantile Spasms: A Single-center Parallel-Cohort Randomized Controlled Trial","volume":"60","author":"Dressler","year":"2019","journal-title":"Epilepsia"},{"key":"B8","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s11011-017-0150-x","article-title":"Pyridoxine-dependent Epilepsies: an Observational Study on Clinical, Diagnostic, Therapeutic and Prognostic Features in a Pediatric Cohort","volume":"33","author":"Falsaperla","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"621200","DOI":"10.3389\/fped.2021.621200","article-title":"West Syndrome Is an Exceptional Presentation of Pyridoxine- and Pyridoxal Phosphate-dependent Epilepsy: Data from a French Cohort and Review of the Literature","volume":"9","author":"Gibaud","year":"2021","journal-title":"Front. Pediatr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1177\/0883073814550829","article-title":"Pyridox(am)ine-5-Phosphate Oxidase Deficiency Treatable Cause of Neonatal Epileptic Encephalopathy with Burst Suppression","volume":"30","author":"Guerin","year":"2015","journal-title":"J. Child. Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.seizure.2015.01.001","article-title":"Long-term Outcomes in Patients with West Syndrome: an Outpatient Clinical Study","volume":"25","author":"G\u00fcveli","year":"2015","journal-title":"Seizure"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/jmd2.12183","article-title":"Early\u2010onset Vitamin B 6 \u2010dependent Epilepsy Due to Pathogenic PLPBP Variants in a Premature Infant: A Case Report and Review of the Literature","volume":"58","author":"Heath","year":"2020","journal-title":"JIMD Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1542\/peds.13.2.140","article-title":"Pyridoxine Dependency: Report of a Case of Intractable Convulsions in an Infant Controlled by Pyridoxine","volume":"13","author":"Hunt","year":"1954","journal-title":"Pediatrics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/dmcn.14385","article-title":"Clinical and Genetic Features in Pyridoxine\u2010dependent Epilepsy: a Chinese Cohort Study","volume":"62","author":"Jiao","year":"2020","journal-title":"Dev. Med. Child. Neurol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"385","DOI":"10.4103\/0028-3886.227281","article-title":"Addition of Pyridoxine to Prednisolone in the Treatment of Infantile Spasms: a Pilot, Randomized Controlled Trial","volume":"66","author":"Kunnanayaka","year":"2018","journal-title":"Neurol. India"},{"key":"B16","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.braindev.2020.02.005","article-title":"Electroclinical Variability of Pyridoxine-dependent Epilepsy Caused by ALDH7A1 Gene Mutations in Four Taiwanese Children","volume":"42","author":"Lee","year":"2020","journal-title":"Brain Develop."},{"key":"B17","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1212\/wnl.0000000000001883","article-title":"Intragenic Deletions ofALDH7A1in Pyridoxine-dependent Epilepsy Caused byAlu-Alurecombination","volume":"85","author":"Mefford","year":"2015","journal-title":"Neurology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1093\/brain\/awu051","article-title":"Epilepsy Due to PNPO Mutations: Genotype, Environment and Treatment Affect Presentation and Outcome","volume":"137","author":"Mills","year":"2014","journal-title":"Brain"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.1093\/brain\/awq143","article-title":"Genotypic and Phenotypic Spectrum of Pyridoxine-dependent Epilepsy (ALDH7A1 Deficiency)","volume":"133","author":"Mills","year":"2010","journal-title":"Brain"},{"key":"B20","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nm1366","article-title":"Mutations in Antiquitin in Individuals with Pyridoxine-dependent Seizures","volume":"12","author":"Mills","year":"2006","journal-title":"Nat. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1093\/hmg\/ddi120","article-title":"Neonatal Epileptic Encephalopathy Caused by Mutations in the PNPO Gene Encoding Pyridox(am)ine 5\u2032-phosphate Oxidase","volume":"14","author":"Mills","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"100357","DOI":"10.1016\/j.ebr.2020.100357","article-title":"Variable Treatment Response in a Patient with Pyridoxal N Phosphate Oxidase (PNPO) Deficiency- Understanding the Paradox","volume":"14","author":"Mohanlal","year":"2020","journal-title":"Epilepsy Behav. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.braindev.2011.01.010","article-title":"Vitamin B6 Treatment of Intractable Seizures","volume":"33","author":"Ohtahara","year":"2011","journal-title":"Brain Develop."},{"key":"B24","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/ana.24883","article-title":"Genetics and Genotype-Phenotype Correlations in Early Onset Epileptic Encephalopathy with Burst Suppression","volume":"81","author":"Olson","year":"2017","journal-title":"Ann. Neurol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1111\/epi.12083","article-title":"Clinical, Biochemical, and Molecular Studies in Pyridoxine-dependent Epilepsy. Antisense Therapy as Possible New Therapeutic Option","volume":"54","author":"P\u00e9rez","year":"2013","journal-title":"Epilepsia"},{"key":"B26","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1136\/jmedgenet-2017-104521","article-title":"Confirmation of Mutations inPROSCas a Novel Cause of Vitamin B6-dependent Epilepsy","volume":"54","author":"Plecko","year":"2017","journal-title":"J. Med. Genet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: a Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.pediatrneurol.2020.01.015","article-title":"Infantile Spasms: Outcome in Clinical Studies","volume":"108","author":"Riikonen","year":"2020","journal-title":"Pediatr. Neurol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1111\/j.1528-1157.1996.tb00573.x","article-title":"Long-Term Outcome of West Syndrome: A Study of Adults with a History of Infantile Spasms","volume":"37","author":"Riikonen","year":"1996","journal-title":"Epilepsia"},{"key":"B30","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1007\/s10545-010-9187-2","article-title":"The Genotypic and Phenotypic Spectrum of Pyridoxine-dependent Epilepsy Due to Mutations in ALDH7A1","volume":"33","author":"Scharer","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1111\/epi.13709","article-title":"ILAE Classification of the Epilepsies: Position Paper of the ILAE Commission for Classification and Terminology","volume":"58","author":"Scheffer","year":"2017","journal-title":"Epilepsia"},{"key":"B32","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.ymgme.2011.05.014","article-title":"Pyridoxine Dependent Epilepsy and Antiquitin Deficiency: Clinical and Molecular Characteristics and Recommendations for Diagnosis, Treatment and Follow-Up","volume":"104","author":"Stockler","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"B33","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.gene.2013.01.041","article-title":"Pyridoxine-dependent Epilepsy in Tunisia Is Caused by a Founder Missense Mutation of the ALDH7A1 Gene","volume":"518","author":"Tlili","year":"2013","journal-title":"Gene"},{"key":"B34","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.pediatrneurol.2015.12.013","article-title":"Pyridoxine-Dependent Epilepsy: An Expanding Clinical Spectrum","volume":"59","author":"van Karnebeek","year":"2016","journal-title":"Pediatr. Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1007\/s11011-017-9995-2","article-title":"Novel phenotypes of pyridox(am)ine-5'-phosphate oxidase deficiency and high prevalence of c.445_448del mutation in Chinese patients","volume":"32","author":"Xue","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1007\/s12519-018-0127-9","article-title":"Clinical Characteristics of Two Cohorts of Infantile Spasms: Response to Pyridoxine or Topiramate Monotherapy","volume":"14","author":"Xue","year":"2018","journal-title":"World J. Pediatr."},{"key":"B37","doi-asserted-by":"publisher","first-page":"E113","DOI":"10.1111\/j.1440-1754.2010.01866.x","article-title":"Pyridoxine-dependent Epilepsy: an Under-recognised Cause of Intractable Seizures","volume":"48","author":"Yeghiazaryan","year":"2012","journal-title":"J. paediatrics child Health"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.804461\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T04:47:14Z","timestamp":1649738834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.804461\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,12]]},"references-count":37,"alternative-id":["10.3389\/fgene.2022.804461"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.804461","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,12]]},"article-number":"804461"}}