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We hypothesize that nonsyndromic or \u201cessential\u201d autism involves extreme male bias in infants who are genetically normal, but they develop deficiency of carnitine and perhaps other nutrients in the brain causing autism that may be amenable to early reversal and prevention. That brain carnitine deficiency might cause autism is suggested by reports of severe carnitine deficiency in autism and by evidence that <jats:italic>TMLHE<\/jats:italic> deficiency \u2212 a defect in carnitine biosynthesis \u2212 is a risk factor for autism. A gene on the X chromosome (<jats:italic>SLC6A14<\/jats:italic>) likely escapes random X\u2010inactivation (a mixed epigenetic and genetic regulation) and could limit carnitine transport across the blood\u2010brain barrier in boys compared to girls. A mixed, common gene variant\u2010environment hypothesis is proposed with diet, minor illnesses, microbiome, and drugs as possible risk modifiers. The hypothesis can be tested using animal models and by a trial of carnitine supplementation in siblings of probands. Perhaps the lack of any Recommended Dietary Allowance for carnitine in infants should be reviewed. Also see the video abstract here: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/youtu.be\/BuRH_jSjX5Y\">https:\/\/youtu.be\/BuRH_jSjX5Y<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1002\/bies.201700012","type":"journal-article","created":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T10:40:08Z","timestamp":1499942408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias: A hypothesis"],"prefix":"10.1002","volume":"39","author":[{"given":"Arthur L.","family":"Beaudet","sequence":"first","affiliation":[{"name":"Departments of Molecular and Human Genetics and Pediatrics Baylor College of Medicine Texas Children's Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,13]]},"reference":[{"key":"e_1_2_22_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120210109"},{"key":"e_1_2_22_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00081-7"},{"key":"e_1_2_22_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/302497"},{"key":"e_1_2_22_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138659"},{"key":"e_1_2_22_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13908"},{"key":"e_1_2_22_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3585"},{"key":"e_1_2_22_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000410)91:4<245::AID-AJMG1>3.0.CO;2-2"},{"key":"e_1_2_22_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37192"},{"key":"e_1_2_22_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.01.004"},{"key":"e_1_2_22_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.317.5835.190"},{"key":"e_1_2_22_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00345"},{"key":"e_1_2_22_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-9877(98)90270-5"},{"key":"e_1_2_22_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-004-5283-1"},{"key":"e_1_2_22_15_1","first-page":"179","article-title":"Polyunsaturated fatty acids, carnitine and lactate as biological markers of brain energy in autistic children","volume":"2","author":"Mostafa GA","year":"2005","journal-title":"Int J Child Neuropsychiatry"},{"key":"e_1_2_22_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12993-014-0048-2"},{"key":"e_1_2_22_17_1","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174415001439"},{"key":"e_1_2_22_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-008-0583-5"},{"key":"e_1_2_22_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181c5e6f7"},{"key":"e_1_2_22_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.12.015"},{"key":"e_1_2_22_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00174"},{"key":"e_1_2_22_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2008.05.013"},{"key":"e_1_2_22_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160510061"},{"key":"e_1_2_22_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2015.10.019"},{"key":"e_1_2_22_25_1","article-title":"The potential relevance of docosahexaenoic acid and eicosapentaenoic acid to the etiopathogenesis of childhood neuropsychiatric disorders","author":"Tesei A","year":"2016","journal-title":"Eur Child Adolesc Psychiatry"},{"key":"e_1_2_22_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0899-9007(95)00068-2"},{"key":"e_1_2_22_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32835ee548"},{"key":"e_1_2_22_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001081"},{"key":"e_1_2_22_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1115455"},{"key":"e_1_2_22_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705803104"},{"key":"e_1_2_22_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.05.015"},{"key":"e_1_2_22_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.08.122"},{"key":"e_1_2_22_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.229518"},{"key":"e_1_2_22_34_1","first-page":"G1463","article-title":"Molecular and functional characterization of intestinal Na(+)\u2010dependent neutral amino acid transporter B0","volume":"272","author":"Kekuda R","year":"1997","journal-title":"Am J Physiol"},{"key":"e_1_2_22_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0297f.x"},{"key":"e_1_2_22_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02752.x"},{"key":"e_1_2_22_37_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-13-RG-058"},{"key":"e_1_2_22_38_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/BF03542994","article-title":"L\u2010carnitine as essential methylated compound in animal metabolism. 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