{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T22:08:27Z","timestamp":1788473307997,"version":"build-2803163510"},"reference-count":82,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Arizona Biomedical Research Centre","award":["No number"],"award-info":[{"award-number":["No number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Neurodevelopmental disorders are associated with metabolic pathway imbalances; however, most metabolic measurements are made peripherally, leaving central metabolic disturbances under-investigated. Cerebrospinal fluid obtained intraoperatively from children with autism spectrum disorder (ASD, n = 34), developmental delays (DD, n = 20), and those without known DD\/ASD (n = 34) was analyzed using large-scale targeted mass spectrometry. Eighteen also had epilepsy (EPI). Metabolites significantly related to ASD, DD and EPI were identified by linear models and entered into metabolite\u2013metabolite network pathway analysis. Common disrupted pathways were analyzed for each group of interest. Central metabolites most involved in metabolic pathways were L-cysteine, adenine, and dodecanoic acid for ASD; nicotinamide adenine dinucleotide phosphate, L-aspartic acid, and glycine for EPI; and adenosine triphosphate, L-glutamine, ornithine, L-arginine, L-lysine, citrulline, and L-homoserine for DD. Amino acid and energy metabolism pathways were most disrupted in all disorders, but the source of the disruption was different for each disorder. Disruption in vitamin and one-carbon metabolism was associated with DD and EPI, lipid pathway disruption was associated with EPI and redox metabolism disruption was related to ASD. Two microbiome metabolites were also detected in the CSF: shikimic and cis-cis-muconic acid. Overall, this study provides increased insight into unique metabolic disruptions in distinct but overlapping neurodevelopmental disorders.<\/jats:p>","DOI":"10.3390\/metabo12050371","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T03:46:11Z","timestamp":1650512771000},"page":"371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Central Nervous System Metabolism in Autism, Epilepsy and Developmental Delays: A Cerebrospinal Fluid Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Danielle","family":"Brister","sequence":"first","affiliation":[{"name":"Barrett, The Honors College, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna A.","family":"Werner","sequence":"additional","affiliation":[{"name":"Section on Neurodevelopmental Disorders, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"},{"name":"Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Gideon","sequence":"additional","affiliation":[{"name":"Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"McCarty","sequence":"additional","affiliation":[{"name":"Section on Neurodevelopmental Disorders, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"},{"name":"Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Lane","sequence":"additional","affiliation":[{"name":"Section on Neurodevelopmental Disorders, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"},{"name":"Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T.","family":"Burrows","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sallie","family":"McLees","sequence":"additional","affiliation":[{"name":"Section on Neurodevelopmental Disorders, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"},{"name":"Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. David","family":"Adelson","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge I.","family":"Arango","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Marsh","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Scottdale, AZ 85259, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelea","family":"Flores","sequence":"additional","affiliation":[{"name":"Department of Pathology, Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Pankratz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Han","family":"Ly","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Flood","sequence":"additional","affiliation":[{"name":"Section on Neurodevelopmental Disorders, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"},{"name":"Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4654-345X","authenticated-orcid":false,"given":"David","family":"Carpentieri","sequence":"additional","affiliation":[{"name":"Department of Pathology, Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jin","sequence":"additional","affiliation":[{"name":"Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwei","family":"Gu","sequence":"additional","affiliation":[{"name":"Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-2937","authenticated-orcid":false,"given":"Richard E.","family":"Frye","sequence":"additional","affiliation":[{"name":"Section on Neurodevelopmental Disorders, Barrow Neurological Institute at Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"},{"name":"Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss6904a1","article-title":"Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years\u2014Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016","volume":"69","author":"Maenner","year":"2020","journal-title":"MMWR Surveill. Summ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S2215-0366(19)30289-5","article-title":"Prevalence of co-occurring mental health diagnoses in the autism population: A systematic review and meta-analysis","volume":"6","author":"Lai","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.5603\/PJNNS.a2021.0047","article-title":"Screening and diagnosis for mood and anxiety disorders in epilepsy: Polish population reference values","volume":"55","author":"Grzegorzewska","year":"2021","journal-title":"Neurol. Neurochir. Polska"},{"key":"ref_4","unstructured":"Armocida, B., Monasta, L., Sawyer, S., Bustreo, F., Segafredo, G., Castelpietra, G., Ronfani, L., Pasovic, M., Hay, S., and Sawyer, S.M. (Lancet Child Adolesc. Health, 2022). Burden of non-communicable diseases among adolescents aged 10\u201324 years in the EU, 1990\u20132019: A systematic analysis of the Global Burden of Diseases Study 2019, Lancet Child Adolesc. Health, in press."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ginsberg, M.R., Rubin, R.A., Falcone, T., Ting, A.H., and Natowicz, M.R. (2012). Brain transcriptional and epigenetic associations with autism. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044736"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3389\/fphys.2014.00150","article-title":"Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism","volume":"5","author":"Rossignol","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.biocel.2016.07.015","article-title":"OxInflammation in Rett syndrome","volume":"81","author":"Pecorelli","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7104","DOI":"10.2174\/0929867325666180510124558","article-title":"Metabolic Routes in Inflammation: The Citrate Pathway and its Potential as Therapeutic Target","volume":"26","author":"Infantino","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Panisi, C., Guerini, F.R., Abruzzo, P.M., Balzola, F., Biava, P.M., Bolotta, A., Brunero, M., Burgio, E., Chiara, A., and Clerici, M. (2021). Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift. J. Pers. Med., 11.","DOI":"10.3390\/jpm11020070"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3389\/fneur.2017.00459","article-title":"Metabolomics as a Tool for the Characterization of Drug-Resistant Epilepsy","volume":"8","author":"Murgia","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1039\/c2mb25105a","article-title":"A metabonomics study of epilepsy in patients using gas chromatography coupled with mass spectrometry","volume":"8","author":"Wei","year":"2012","journal-title":"Mol. Biosyst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.eplepsyres.2016.07.003","article-title":"GC-MS-Based metabolomics discovers a shared serum metabolic characteristic among three types of epileptic seizures","volume":"126","author":"Wang","year":"2016","journal-title":"Epilepsy Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41398-019-0578-3","article-title":"Metabolomics analysis of children with autism, idiopathic-developmental delays, and Down syndrome","volume":"9","author":"Orozco","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"579538","DOI":"10.3389\/fpsyt.2020.579538","article-title":"Association between Plasma Metabolites and Psychometric Scores Among Children With Developmental Disabilities: Investigating Sex-Differences","volume":"11","author":"Abbeduto","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.biopsych.2020.09.025","article-title":"Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder","volume":"89","author":"Needham","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.anaerobe.2017.12.007","article-title":"Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders","volume":"49","author":"Kang","year":"2018","journal-title":"Anaerobe"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D.I., Cristofori, F., Guerzoni, M.E., Gobbetti, M., and Francavilla, R. (2013). Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076993"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Qureshi, F., Adams, J., Hanagan, K., Kang, D.W., Krajmalnik-Brown, R., and Hahn, J. (2020). Multivariate Analysis of Fecal Metabolites from Children with Autism Spectrum Disorder and Gastrointestinal Symptoms before and after Microbiota Transfer Therapy. J. Pers. Med., 10.","DOI":"10.3390\/jpm10040152"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1021\/pr300910n","article-title":"Metabolic perturbance in autism spectrum disorders: A metabolomics study","volume":"11","author":"Ming","year":"2012","journal-title":"J Proteome Res"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"165859","DOI":"10.1016\/j.bbadis.2020.165859","article-title":"A metabolomics approach to investigate urine levels of neurotransmitters and related metabolites in autistic children","volume":"1866","author":"Gevi","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"792319","DOI":"10.3389\/fmolb.2021.792319","article-title":"Urine Organic Acids as Metabolic Indicators for Global Developmental Delay\/Intellectual Disability in Chinese Children","volume":"8","author":"Chen","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_22","first-page":"65","article-title":"Metabolic Profiling of the Cerebrospinal Fluid in Pediatric Epilepsy","volume":"74","author":"Akiyama","year":"2020","journal-title":"Acta Med. Okayama"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s11306-020-01685-z","article-title":"Targeted metabolomics highlights perturbed metabolism in the brain of autism spectrum disorder sufferers","volume":"16","author":"Graham","year":"2020","journal-title":"Metabolomics"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lalwani, A.M., Yilmaz, A., Bisgin, H., Ugur, Z., Akyol, S., and Graham, S.F. (2020). Biochemical Profile of Post-Mortem Brain from People Who Suffered from Epilepsy Reveals Novel Insights into the Etiopathogenesis of the Disease. Metabolites, 10.","DOI":"10.3390\/metabo10060261"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/mp.2010.136","article-title":"Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis","volume":"17","author":"Rossignol","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s40291-018-0352-x","article-title":"Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder","volume":"22","author":"Rose","year":"2018","journal-title":"Mol. Diagn. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"636","DOI":"10.3389\/fpsyt.2018.00636","article-title":"A Subset of Patients With Autism Spectrum Disorders Show a Distinctive Metabolic Profile by Dried Blood Spot Analyses","volume":"9","author":"Barone","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e220","DOI":"10.1038\/tp.2012.143","article-title":"Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder","volume":"3","author":"Frye","year":"2013","journal-title":"Transl. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/ajmg.b.30366","article-title":"Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism","volume":"141B","author":"James","year":"2006","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"321","DOI":"10.2217\/bmm.13.158","article-title":"Metabolic pathology of autism in relation to redox metabolism","volume":"8","author":"Frye","year":"2014","journal-title":"Biomark. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Howsmon, D.P., Kruger, U., Melnyk, S., James, S.J., and Hahn, J. (2017). Classification and adaptive behavior prediction of children with autism spectrum disorder based upon multivariate data analysis of markers of oxidative stress and DNA methylation. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005385"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/btm2.10095","article-title":"Multivariate techniques enable a biochemical classification of children with autism spectrum disorder versus typically-developing peers: A comparison and validation study","volume":"3","author":"Howsmon","year":"2018","journal-title":"Bioeng. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3389\/fncel.2018.00503","article-title":"Comparison of Three Clinical Trial Treatments for Autism Spectrum Disorder Through Multivariate Analysis of Changes in Metabolic Profiles and Adaptive Behavior","volume":"12","author":"Vargason","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.biopsych.2018.08.016","article-title":"Amino Acid Dysregulation Metabotypes: Potential Biomarkers for Diagnosis and Individualized Treatment for Subtypes of Autism Spectrum Disorder","volume":"85","author":"Smith","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rossignol, D.A., and Frye, R.E. (2021). Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11111141"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.nurt.2010.05.004","article-title":"Tetrahydrobiopterin as a novel therapeutic intervention for autism","volume":"7","author":"Frye","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e1036","DOI":"10.1002\/mgg3.1036","article-title":"Abnormalities in the genes that encode Large Amino Acid Transporters increase the risk of Autism Spectrum Disorder","volume":"8","author":"Cascio","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6564585","DOI":"10.1155\/2021\/6564585","article-title":"Blood-Brain Barrier Overview: Structural and Functional Correlation","volume":"2021","author":"Alahmari","year":"2021","journal-title":"Neural Plast."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.mito.2013.08.006","article-title":"Metabolic features of the cell danger response","volume":"16","author":"Naviaux","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mito.2017.12.007","article-title":"Antipurinergic therapy for autism-An in-depth review","volume":"43","author":"Naviaux","year":"2018","journal-title":"Mitochondrion"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/j.bbalip.2013.06.007","article-title":"Peroxisomes contribute to the acylcarnitine production when the carnitine shuttle is deficient","volume":"1831","author":"Violante","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Koju, N., Qin, Z.H., and Sheng, R. (2022). Reduced nicotinamide adenine dinucleotide phosphate in redox balance and diseases: A friend or foe?. Acta Pharmacol. Sin.","DOI":"10.1038\/s41401-021-00838-7"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1124\/dmd.112.048991","article-title":"NADPH-cytochrome P450 oxidoreductase: Roles in physiology, pharmacology, and toxicology","volume":"41","author":"Riddick","year":"2013","journal-title":"Drug Metab. Dispos."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/ars.2000.2.2-251","article-title":"NADH and NADPH-dependent reduction of coenzyme Q at the plasma membrane","volume":"2","author":"Arroyo","year":"2000","journal-title":"Antioxid. Redox Signal."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.freeradbiomed.2013.07.036","article-title":"The thioredoxin antioxidant system","volume":"66","author":"Lu","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/jcp.24926","article-title":"MNADK, a Long-Awaited Human Mitochondrion-Localized NAD Kinase","volume":"230","author":"Zhang","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"770","DOI":"10.4103\/aian.AIAN_1282_20","article-title":"Late Diagnosis of Pyridoxine-Dependent Epilepsy in Two Adolescent Siblings","volume":"24","author":"Isikay","year":"2021","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.seizure.2021.07.014","article-title":"Is oxidative stress an overlooked player in pyridoxine-dependent epilepsy? A focused review","volume":"91","author":"Yazdani","year":"2021","journal-title":"Seizure"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bugiardini, E., Pope, S., Feichtinger, R.G., Poole, O.V., Pittman, A.M., Woodward, C.E., Heales, S., Quinlivan, R., Houlden, H., and Mayr, J.A. (2019). Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases. J. Clin. Med., 8.","DOI":"10.3390\/jcm8070991"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"567","DOI":"10.4103\/jfmpc.jfmpc_1466_20","article-title":"Seizure as a presenting manifestation of Wernicke\u2019s encephalopathy induced by hyperemesis gravidarum","volume":"10","author":"Ghosh","year":"2021","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/1028415X.2017.1357919","article-title":"Anticonvulsant effects of thiamine on pentylenetetrazole-induced seizure in mice","volume":"22","author":"Mesdaghinia","year":"2019","journal-title":"Nutr. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1089\/ars.2011.4357","article-title":"Mitoplasticity: Adaptation biology of the mitochondrion to the cellular redox state in physiology and carcinogenesis","volume":"18","author":"Jose","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41R","DOI":"10.1203\/PDR.0b013e318212f16b","article-title":"Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders","volume":"69","author":"Frye","year":"2011","journal-title":"Pediatr. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10","DOI":"10.13172\/2052-7810-1-1-433","article-title":"Mitochondrial physiology and autism spectrum disorder","volume":"1","author":"Frye","year":"2013","journal-title":"OA Autism"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.mito.2009.09.006","article-title":"Energetics, epigenetics, mitochondrial genetics","volume":"10","author":"Wallace","year":"2010","journal-title":"Mitochondrion"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3389\/fnins.2016.00192","article-title":"Neuropathological Mechanisms of Seizures in Autism Spectrum Disorder","volume":"10","author":"Frye","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1126\/science.1224631","article-title":"Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy","volume":"338","author":"Novarino","year":"2012","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"364976","DOI":"10.1155\/2014\/364976","article-title":"Metabolic and Physiological Roles of Branched-Chain Amino Acids","volume":"2014","author":"Monirujjaman","year":"2014","journal-title":"Adv. Mol. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rossignol, D.A., and Frye, R.E. (2021). The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11080784"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.neubiorev.2015.04.015","article-title":"Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review","volume":"55","author":"Slattery","year":"2015","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12986-022-00653-9","article-title":"Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: A meta-analysis","volume":"19","author":"Zhong","year":"2022","journal-title":"Nutr. metab."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wagner, S., Manickam, R., Brotto, M., and Tipparaju, S.M. (2022). NAD(+) centric mechanisms and molecular determinants of skeletal muscle disease and aging. Mol. Cell. Biochem.","DOI":"10.1007\/s11010-022-04408-1"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.cmet.2022.02.001","article-title":"The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson\u2019s disease","volume":"34","author":"Brakedal","year":"2022","journal-title":"Cell Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"159094","DOI":"10.1016\/j.bbalip.2021.159094","article-title":"NAD supplementation improves mitochondrial performance of cardiolipin mutants","volume":"1867","author":"Ji","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.neubiorev.2021.07.001","article-title":"Altering the gut microbiome to potentially modulate behavioral manifestations in autism spectrum disorders: A systematic review","volume":"128","author":"Davies","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_66","first-page":"28177","article-title":"Enteric short-chain fatty acids: Microbial messengers of metabolism, mitochondria, and mind: Implications in autism spectrum disorders","volume":"26","author":"MacFabe","year":"2015","journal-title":"Microb. Ecol. Health Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"91","DOI":"10.4137\/CMPed.S38338","article-title":"The Significance of the Enteric Microbiome on the Development of Childhood Disease: A Review of Prebiotic and Probiotic Therapies in Disorders of Childhood","volume":"10","author":"Slattery","year":"2016","journal-title":"Clin. Med. Insights Pediatr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e927","DOI":"10.1038\/tp.2016.189","article-title":"Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines","volume":"6","author":"Frye","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41398-017-0089-z","article-title":"Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism","volume":"8","author":"Rose","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/jocd.14136","article-title":"Shikimic acid in the light of current knowledge","volume":"21","author":"Batory","year":"2022","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_71","first-page":"701","article-title":"Antagonistic effects of shikimic acid against focal cerebral ischemia injury in rats subjected to middle cerebral artery thrombosis","volume":"20","author":"Ma","year":"1999","journal-title":"Zhongguo Yao Li Xue Bao Acta Pharmacol. Sin."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s12264-018-0322-7","article-title":"Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice","volume":"35","author":"Lu","year":"2019","journal-title":"Neurosci. Bull."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Choi, S., Lee, H.N., Park, E., Lee, S.J., and Kim, E.S. (2020). Recent Advances in Microbial Production of cis,cis-Muconic Acid. Biomol., 10.","DOI":"10.3390\/biom10091238"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s11306-018-1333-0","article-title":"Strategies to assess and optimize stability of endogenous amines during cerebrospinal fluid sampling","volume":"14","author":"Noga","year":"2018","journal-title":"Metabolomics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"12355","DOI":"10.1021\/acs.analchem.5b03812","article-title":"Globally Optimized Targeted Mass Spectrometry: Reliable Metabolomics Analysis with Broad Coverage","volume":"87","author":"Gu","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15646","DOI":"10.1002\/anie.201609236","article-title":"Quantitative Method to Investigate the Balance between Metabolism and Proteome Biomass: Starting from Glycine","volume":"55","author":"Gu","year":"2016","journal-title":"Angew. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"13737","DOI":"10.1021\/acs.analchem.9b03107","article-title":"Database-Assisted Globally Optimized Targeted Mass Spectrometry (dGOT-MS): Broad and Reliable Metabolomics Analysis with Enhanced Identification","volume":"91","author":"Shi","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1021\/acs.jproteome.9b00100","article-title":"Coccidioidomycosis Detection Using Targeted Plasma and Urine Metabolic Profiling","volume":"18","author":"Jasbi","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1021\/acs.jproteome.0c00038","article-title":"Triple Negative Breast Cancer Detection Using LC-MS\/MS Lipidomic Profiling","volume":"19","author":"Eghlimi","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4303","DOI":"10.1021\/acs.jproteome.1c00290","article-title":"Metabolic Profiling of Neocortical Tissue Discriminates Alzheimer\u2019s Disease from Mild Cognitive Impairment, High Pathology Controls, and Normal Controls","volume":"20","author":"Jasbi","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s13059-019-1790-4","article-title":"Identifying significantly impacted pathways: A comprehensive review and assessment","volume":"20","author":"Nguyen","year":"2019","journal-title":"Genome Biol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/5\/371\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:57:13Z","timestamp":1760137033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/5\/371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,20]]},"references-count":82,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["metabo12050371"],"URL":"https:\/\/doi.org\/10.3390\/metabo12050371","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,20]]}}}