{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T19:12:03Z","timestamp":1770577923785,"version":"3.49.0"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"06","funder":[{"name":"Children's Research Center","award":["protected time 2020 - program"],"award-info":[{"award-number":["protected time 2020 - program"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To describe a new phenotype and the diagnostic workup of a vitamin-B6-dependent epilepsy due to pyridoxal 5\u2032-phosphate-binding protein (PLPBP) deficiency in an infant with early-onset epilepsy at the age of 5 years 6 months. Following immediate and impressive clinical response to treatment with pyridoxine, metabolic screening for vitamin-B6-dependent epilepsies and targeted next-generation sequencing (NGS)-based gene panel analysis were performed. Potentially pathogenic variants were confirmed by Sanger sequencing in the patient, and variants were analyzed in both parents to confirm biallelic inheritance. The clinical phenotype and course of disease were compared to the 44 cases reported in the literature, harboring variants in pyridoxal phosphate homeostasis protein (PLPHP) and with cases of vitamin-B6-dependent epilepsy due to other known causative genes. Levels of alpha-aminoadipic semialdehyde in urine and amino acids were normal. Two inherited pathogenic variations in PLPHP were found in compound heterozygosity, including one novel deletion. We here describe a previously unreported individual harboring biallelic pathogenic PLPHP variants presenting with paroxysmal eye\u2013head movements followed by epileptic spasms and an almost normal interictal electroencephalogram, thus expanding the clinical spectrum of PLPBP deficiency. This warrants consideration of vitamin-B6-dependent epilepsies in patients with early-onset epilepsy, including epileptic spasms, and eye movement disorders also beyond the neonatal period even when metabolic screening for vitamin-B6-dependent epilepsies is negative. PLPHP should be included systematically in NGS epilepsy gene panels.<\/jats:p>","DOI":"10.1055\/a-2003-9886","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:01:56Z","timestamp":1672272116000},"page":"422-425","source":"Crossref","is-referenced-by-count":2,"title":["Infantile Spasms without Hypsarrhythmia and Paroxysmal Eye\u2013Head Movements in an Infant with a Pyridoxine-Dependent Epilepsy due to PLPBP\/PLPHP Deficiency"],"prefix":"10.1055","volume":"54","author":[{"given":"Judith","family":"Kalser","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neurorehabilitation Unit, Department of Woman-Mother-Child, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabienne","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Peralta","sequence":"additional","affiliation":[{"name":"Pediatric Unit for Metabolic Diseases, Department of Woman-Mother-Child, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Plecko","sequence":"additional","affiliation":[{"name":"Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0008-3339","authenticated-orcid":false,"given":"Bigna K.","family":"B\u00f6lsterli","sequence":"additional","affiliation":[{"name":"Child Development Center, University Children's Hospital Zurich, Zurich, Switzerland"},{"name":"Department of Pediatric Neurology, University Children's Hospital Zurich, Zurich, Switzerland"},{"name":"Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland"},{"name":"Department of Pediatric Neurology, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.amsu.2020.11.079","article-title":"Vitamin B6-dependent epilepsy due to pyridoxal phosphate-binding protein (PLPBP) defect - first case report from Pakistan and review of literature","volume":"60","author":"S Ahmed","year":"2020","journal-title":"Ann Med Surg (Lond)"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1055\/s-0039-1685501","article-title":"Excessive seizure clusters in an otherwise well-controlled epilepsy as a possible hallmark of untreated vitamin B6-responsive epilepsy due to a homozygous PLPBP missense variant","volume":"8","author":"J Johannsen","year":"2019","journal-title":"J Pediatr Genet"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/jmd2.12196","article-title":"A founder mutation in the PLPBP gene in families from Saguenay-Lac-St-Jean region affected by a pyridoxine-dependent epilepsy","volume":"59","author":"M Pal","year":"2021","journal-title":"JIMD Rep"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jmd2.12183","article-title":"Early-onset vitamin B6-dependent epilepsy due to pathogenic PLPBP variants in a premature infant: a case report and review of the literature","volume":"58","author":"O Heath","year":"2020","journal-title":"JIMD Rep"},{"issue":"04","key":"ref5","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/jimd.12060","article-title":"Disorders affecting vitamin B6 metabolism","volume":"42","author":"M P Wilson","year":"2019","journal-title":"J Inherit Metab Dis"},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.seizure.2010.11.018","article-title":"Infantile spams without hypsarrhythmia: a study of 16 cases","volume":"20","author":"R H Caraballo","year":"2011","journal-title":"Seizure"},{"issue":"02","key":"ref7","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1684\/epd.2015.0738","article-title":"Epileptic spasms without hypsarrhythmia in infancy and childhood: tonic spasms as a seizure type","volume":"17","author":"L R Marchi","year":"2015","journal-title":"Epileptic Disord"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"804461","DOI":"10.3389\/fgene.2022.804461","article-title":"A rare presentation characterized by epileptic spasms in ALDH7A1, pyridox(am)ine-5\u2032-phosphate oxidase, and PLPBP deficiency","volume":"13","author":"X Jiao","year":"2022","journal-title":"Front Genet"},{"key":"ref9","doi-asserted-by":"crossref","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":"M Gibaud","year":"2021","journal-title":"Front Pediatr"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1099\/mic.0.000255","article-title":"Evidence that COG0325 proteins are involved in PLP homeostasis","volume":"162","author":"L Prunetti","year":"2016","journal-title":"Microbiology (Reading)"},{"issue":"03","key":"ref11","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1093\/brain\/awy346","article-title":"PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights","volume":"142","author":"D L Johnstone","year":"2019","journal-title":"Brain"},{"issue":"02","key":"ref12","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/epi4.12055","article-title":"Gene panel analysis for nonsyndromic cryptogenic neonatal\/infantile epileptic encephalopathy","volume":"2","author":"C W Fung","year":"2017","journal-title":"Epilepsia Open"},{"key":"ref13","doi-asserted-by":"crossref","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":"P B Mills","year":"2014","journal-title":"Brain"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1055\/s-0039-1697775","article-title":"Pyridoxine responsive seizures: beyond aldehyde dehydrogenase 7a1","volume":"10","author":"R Koul","year":"2019","journal-title":"J Neurosci Rural Pract"},{"issue":"17","key":"ref15","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1212\/WNL.0000000000003867","article-title":"Paroxysmal eye-head movements in Glut1 deficiency syndrome","volume":"88","author":"T S Pearson","year":"2017","journal-title":"Neurology"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2003-9886.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T23:37:15Z","timestamp":1699918635000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2003-9886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,28]]},"references-count":15,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2023,11,13]]},"published-print":{"date-parts":[[2023,12]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2003-9886","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,12,28]]},"published":{"date-parts":[[2022,12,28]]}}}