{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T23:25:58Z","timestamp":1781306758705,"version":"3.54.1"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T00:00:00Z","timestamp":1550793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pyridoxine dependent epilepsy (PDE) is a treatable epileptic encephalopathy characterized by a positive response to pharmacologic doses of pyridoxine. Despite seizure control, at least 75% of individuals have intellectual disability and developmental delay. Current treatment paradigms have resulted in improved cognitive outcomes emphasizing the importance of an early diagnosis. As genetic testing is increasingly accepted as first tier testing for epileptic encephalopathies, we aimed to provide a comprehensive overview of <jats:italic>ALDH7A1<\/jats:italic> mutations that cause PDE. The genotypes, ethnic origin and reported gender was collected from 185 subjects with a diagnosis of PDE. The population frequency for the variants in this report and the existing literature were reviewed in the Genome Aggregation Database (gnomAD). Novel variants identified in population databases were also evaluated through in silico prediction software and select variants were over\u2010expressed in an <jats:italic>E.coli<\/jats:italic>\u2010based expression system to measure \u03b1\u2010aminoadipic semialdehyde dehydrogenase activity and production of \u03b1\u2010aminoadipic acid. This study adds 47 novel variants to the literature resulting in a total of 165 reported pathogenic variants. Based on this report, in silico predictions, and general population data, we estimate an incidence of approximately 1:64,352 live births. This report provides a comprehensive overview of known <jats:italic>ALDH7A1<\/jats:italic> mutations that cause PDE, and suggests that PDE may be more common than initially estimated. Due to the relative high frequency of the disease, the likelihood of under\u2010diagnosis given the wide clinical spectrum and limited awareness among clinicians as well as the cognitive improvement noted with early treatment, newborn screening for PDE may be warranted.<\/jats:p>","DOI":"10.1002\/jimd.12045","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T11:57:54Z","timestamp":1550836674000},"page":"353-361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["The genotypic spectrum of <i>ALDH7A1<\/i> mutations resulting in pyridoxine dependent epilepsy: A common epileptic encephalopathy"],"prefix":"10.1002","volume":"42","author":[{"suffix":"II","given":"Curtis R.","family":"Coughlin","sequence":"first","affiliation":[{"name":"Section of Clinical Genetics and Metabolism, Department of Pediatrics University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Swanson","sequence":"additional","affiliation":[{"name":"Section of Clinical Genetics and Metabolism, Department of Pediatrics University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Spector","sequence":"additional","affiliation":[{"name":"Section of Clinical Genetics and Metabolism, Department of Pediatrics University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"Molecular Genetics Laboratory, Department of Pathology and Laboratory Medicine Children's Hospital Colorado  Aurora Colorado 80045 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi J. L.","family":"Meeks","sequence":"additional","affiliation":[{"name":"Section of Clinical Genetics and Metabolism, Department of Pediatrics University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"Molecular Genetics Laboratory, Department of Pathology and Laboratory Medicine Children's Hospital Colorado  Aurora Colorado 80045 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E.","family":"Kronquist","sequence":"additional","affiliation":[{"name":"Section of Clinical Genetics and Metabolism, Department of Pediatrics University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"Molecular Genetics Laboratory, Department of Pathology and Laboratory Medicine Children's Hospital Colorado  Aurora Colorado 80045 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mezhgan","family":"Aslamy","sequence":"additional","affiliation":[{"name":"Section of Clinical Genetics and Metabolism, Department of Pediatrics University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Wempe","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Department of Pharmaceutical Sciences University of Colorado, Anschutz Medical Campus  Aurora Colorado 80045 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara D. M.","family":"van Karnebeek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Clinical Genetics Academic Medical Centre  1105 AZ Amsterdam The Netherlands"},{"name":"Department of Pediatrics, Centre for Molecular Medicine and Therapeutics University of British Columbia  Vancouver British Columbia V5Z4H4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Sidney M.","family":"Gospe","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Departments of Neurology and Pediatrics University of Washington  Seattle Washington USA"},{"name":"Seattle Children's Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena G.","family":"Aziz","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becky P.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Fulgent Genetics  Temple City California 91780 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlin","family":"Gao","sequence":"additional","affiliation":[{"name":"Fulgent Genetics  Temple City California 91780 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Nagy","sequence":"additional","affiliation":[{"name":"Medical Neurogenetics Laboratories, LLC  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Hyland","sequence":"additional","affiliation":[{"name":"Medical Neurogenetics Laboratories, LLC  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvy J. 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