{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:17:28Z","timestamp":1783959448470,"version":"3.55.0"},"reference-count":45,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Rare Disease"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Pyridoxine-dependent epilepsy (PDE) due to biallelic pathogenic variants in\n                      <jats:italic toggle=\"yes\">ALDH7A1<\/jats:italic>\n                      (PDE-ALDH7A1) is an metabolic disease of lysine catabolism. Current standard treatment includes pyridoxine, arginine, and lysine- or protein-restricted diet. Pyridoxine treats seizures. Arginine and lysine- or protein-restricted diet decrease elevated \u03b1-aminoadipic semialdehyde (\u03b1-AASA) and \u03941- piperideine-6-carboxylate (P6C) levels to improve neurodevelopmental outcomes. We previously reported abnormalities in tricarboxylic acid (TCA) cycle and electron transport chain in PDE-ALDH7A1. We report a new patient with PDE-ALDH7A1 who did not show any improvements in neurodevelopment on the current standard therapy. We hypothesized that triheptanoin will provide substrate to TCA cycle and improve abnormal energy metabolism leading to improvements in neurodevelopmental outcome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To treat this patient with triheptanoin to improve neurodevelopmental outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Due to complex I deficiency and lack of response to the current standard therapy, we applied triheptanoin novel therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A 4-year-old male had compound heterozygous variants in\n                      <jats:italic toggle=\"yes\">ALDH7A1<\/jats:italic>\n                      and markedly elevated urine \u03b1-AASA. The goal dose of triheptanoin was 50% of the estimated energy requirement (EER). We assessed efficacy of triheptanoin using neuropsychological assessments. We measured 6-oxopipecolic acid using liquid chromatography tandem mass spectrometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Triheptanoin was started at 10\u2009mL\/day. There was nausea up to 3\u2009weeks after each dose increase, which has improved allowing us to increase triheptanoin gradually. The maximum actual dose of triheptanoin was 40% of EER. Cognitive composite score improved from 16% to 63% on treatment. All chemistry and biochemical investigations were normal. 6-oxopipecolic acid levels did not normalize. Triheptanoin treatment seemed to be safe and tolerated well.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Triheptanoin is an anaplerotic agent to provide substrates to the TCA cycle. This novel therapy improved neurodevelopmental outcome in our patient with PDE-ALDH7A1. We think that trihepatonoin should be the part of the current standard therapy to improve neurodevelopmental outcomes in patients with PDE-ALDH7A1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/26330040261427020","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T16:47:33Z","timestamp":1773247653000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel therapy for pyridoxine-dependent epilepsy due to biallelic pathogenic variants in\n                    <i>ALDH7A1<\/i>\n                    : secondary mitochondrial energy deficiency and improvements of neurodevelopmental outcomes on triheptanoin treatment"],"prefix":"10.1177","volume":"7","author":[{"given":"Anastasia","family":"Ambrose","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Alberta Health Services, Edmonton, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morganne","family":"McCabe","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Alberta Health Services, Edmonton, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Bahl","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada"},{"name":"Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sinasac","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Alberta Children\u2019s Hospital, Alberta Precision Laboratories, Calgary, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Alberta, Edmonton, AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-6764","authenticated-orcid":false,"given":"Saadet","family":"Mercimek-Andrews","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine &amp; Dentistry, University of Alberta, 8-39 Medical Sciences Building, 8613 114 Street, Edmonton, AB T6G 2H7, Canada"},{"name":"Women and Children\u2019s Health Research Institute, Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.05.014"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq143"},{"key":"e_1_3_4_4_2","author":"Gospe SM.","year":"1993","unstructured":"Gospe SM. 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