{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:18:09Z","timestamp":1787242689474,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T00:00:00Z","timestamp":1600214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004052","name":"King Abdullah University of Science and Technology","doi-asserted-by":"publisher","award":["FCC\/1\/1976\u201025"],"award-info":[{"award-number":["FCC\/1\/1976\u201025"]}],"id":[{"id":"10.13039\/501100004052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pyridoxamine\u20105\u2032\u2010phosphate oxidase (PNPO) deficiency is an autosomal recessive pyridoxal 5\u2032\u2010phosphate (PLP)\u2010vitamin\u2010responsive epileptic encephalopathy. The emerging feature of PNPO deficiency is the occurrence of refractory seizures in the first year of life. Pre\u2010maturity and fetal distress, combined with neonatal seizures, are other associated key characteristics. The phenotype results from a dependency of PLP which regulates several enzymes in the body. We present the phenotypic and genotypic spectrum of (PNPO) deficiency based on a literature review (2002\u20102020) of reports (n = 33) of patients with confirmed PNPO deficiency (n = 87). All patients who received PLP (n = 36) showed a clinical response, with a complete dramatic PLP response with seizure cessation observed in 61% of patients. In spite of effective seizure control with PLP, approximately 56% of patients affected with PLP\u2010dependent epilepsy suffer developmental delay\/intellectual disability. There is no diagnostic biomarker, and molecular testing required for diagnosis. However, we noted that cerebrospinal fluid (CSF) PLP was low in 81%, CSF glycine was high in 80% and urinary vanillactic acid was high in 91% of the cases. We observed only a weak correlation between the severity of PNPO protein disruption and disease outcomes, indicating the importance of other factors, including seizure onset and time of therapy initiation. We found that pre\u2010maturity, the delay in initiation of PLP therapy and early onset of seizures correlate with a poor neurocognitive outcome. Given the amenability of PNPO to PLP therapy for seizure control, early diagnosis is essential.<\/jats:p>","DOI":"10.1111\/cge.13843","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T22:51:05Z","timestamp":1599259865000},"page":"99-110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"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"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8317-5951","authenticated-orcid":false,"given":"Malak","family":"Alghamdi","sequence":"first","affiliation":[{"name":"Medical Genetics Division, Department of Pediatrics, College of Medicine King Saud University  Riyadh Saudi Arabia"},{"name":"Department of Pediatrics King Saud University Medical City  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1436-6727","authenticated-orcid":false,"given":"Fahad A.","family":"Bashiri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics King Saud University Medical City  Riyadh Saudi Arabia"},{"name":"Neurology division, Department of Pediatrics, College of Medicine King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Abdelhakim","sequence":"additional","affiliation":[{"name":"Computer, Electrical and Mathematical Science and Engineering Division (CEMSE), Computational Bioscience Research Center (CBRC) King Abdullah University of Science and Technology (KAUST)  Thuwal Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouran","family":"Adly","sequence":"additional","affiliation":[{"name":"College of Medicine Research Center, College of Medicine King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dima Z.","family":"Jamjoom","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging, College of Medicine King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid M.","family":"Sumaily","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Unit, Department of Laboratory Medicine King Saud University Medical City, King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bandar","family":"Alghanem","sequence":"additional","affiliation":[{"name":"Medical Research Core Facility and Platforms (MRCFP) King Abdullah International Medical, Research Center\/King Saud bin Abdulaziz University for Health Sciences (KSAU\u2010HS), King, Abdulaziz Medical City (KAMC), NGHA  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan T.","family":"Arold","sequence":"additional","affiliation":[{"name":"Computational Bioscience, Research Center (CBRC); Division of Biological and Environmental Sciences and Engineering, (BESE) King Abdullah University of Science and Technology (KAUST)  Thuwal Saudi Arabia"},{"name":"Centre de Biochimie Structurale, CNRS, INSERM Universit\u00e9 de Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi120"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-33673"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.304"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.113.005207"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12060"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki031"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.08.003"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-017-9995-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.05.024"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.4238\/2015.October.29.34"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0508-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2012_194"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12346"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24883"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13312-0"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000344"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1697676"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2015_413"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12055"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2020.100357"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2015_482"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2010.03660.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2014_338"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2015_456"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1353489"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.115162"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073814550829"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.11.006"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2016.01.004"},{"issue":"7","key":"e_1_2_8_31_1","first-page":"335","article-title":"Severe fetal anemia and neonatal epileptic encephalopathy caused by a novel PNPO mutation","volume":"65","author":"Lloreda\u2010Garcia JM","year":"2017","journal-title":"Rev Neurol"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073819863992"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2015.08.001"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2010.12.046"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(01)00357-5"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.10.003"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.04.008"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0356203"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4734"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b01358"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12059"},{"issue":"3","key":"e_1_2_8_42_1","first-page":"3S48","article-title":"Value of lumbar puncture in the diagnosis of infantile epilepsy and folinic acid\u2010responsive seizures","volume":"17","author":"Hyland K","year":"2002","journal-title":"J Child Neurol"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01801674"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu051"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13843","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13843","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13843","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T09:44:17Z","timestamp":1693734257000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13843"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,16]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/cge.13843"],"URL":"https:\/\/doi.org\/10.1111\/cge.13843","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.13843\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13843\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13843\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13843\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13843\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13843\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13843\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13843\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13843\/v2\/review1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,16]]},"assertion":[{"value":"2020-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}