Autism and carnitine: A possible link
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摘要
Patients with autism spectrum disorders(ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD have not been defined yet. Many factors seem to be involved in the onset of this disorder. These include genetic and environmental factors, but autism is not linked to a single origin, only. Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency. Carnitine is a derivative of two amino acid lysine and methionine. Carnitine is a cofactor for a large family of enzymes: the carnitine acyltransferases. Through their action these enzymes(and L-carnitine) are involved in energy production and metabolic homeostasis. Some people with autism(less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with Lcarnitine is beneficial. This review summarizes the available information on this topic.
Patients with autism spectrum disorders(ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD have not been defined yet. Many factors seem to be involved in the onset of this disorder. These include genetic and environmental factors, but autism is not linked to a single origin, only. Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency. Carnitine is a derivative of two amino acid lysine and methionine. Carnitine is a cofactor for a large family of enzymes: the carnitine acyltransferases. Through their action these enzymes(and L-carnitine) are involved in energy production and metabolic homeostasis. Some people with autism(less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with Lcarnitine is beneficial. This review summarizes the available information on this topic.
Patients with autism spectrum disorders(ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD have not been defined yet. Many factors seem to be involved in the onset of this disorder. These include genetic and environmental factors, but autism is not linked to a single origin, only. Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency. Carnitine is a derivative of two amino acid lysine and methionine. Carnitine is a cofactor for a large family of enzymes: the carnitine acyltransferases. Through their action these enzymes(and L-carnitine) are involved in energy production and metabolic homeostasis. Some people with autism(less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with Lcarnitine is beneficial. This review summarizes the available information on this topic.
引文
1 American Psychiatric Association:Diagnostic and Statistical Manual of Mental Disorders:Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.Arlington,VA:American Psychiatric Association,2013
2 Lincoln AJ,Courchesne E,Kilman BA,Elmasian R,Allen M.A study of intellectual abilities in high-functioning people with autism.J Autism Dev Disord 1988;18:505-524[PMID:3215879 DOI:10.1007/bf02211870]
3 Baron-Cohen S,Leslie AM,Frith U.Does the autistic child have a"theory of mind"?Cognition1985;21:37-46[PMID:2934210 DOI:10.1016/0010-0277(85)90022-8]
4 HappéF,Frith U.The weak coherence account:detail-focused cognitive style in autism spectrum disorders.J Autism Dev Disord 2006;36:5-25[PMID:16450045 DOI:10.1007/s10803-005-0039-0]
5 Bogdashina O.Sensory perceptual issues in autism and asperger syndrome:different sensory experiences-different perceptual worlds.Jessica Kingsley Publishers.Jessica Kingsley Publishers,2016
6 Fombonne E.Epidemiology of pervasive developmental disorders.Pediatr Res 2009;65:591-598[PMID:19218885 DOI:10.1203/PDR.0b013e31819e7203]
7 Fombonne E.Editorial:The rising prevalence of autism.J Child Psychol Psychiatry 2018;59:717-720[PMID:29924395 DOI:10.1111/jcpp.12941]
8 Grabrucker AM.Environmental factors in autism.Front Psychiatry 2013;3:118[PMID:23346059DOI:10.3389/fpsyt.2012.00118]
9 Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006Principal Investigators;Centers for Disease Control and Prevention(CDC).Prevalence of autism spectrum disorders-Autism and Developmental Disabilities Monitoring Network,United States,2006.MMWR Surveill Summ 2009;58:1-20[PMID:20023608]
10 Ozonoff S,Young GS,Carter A,Messinger D,Yirmiya N,Zwaigenbaum L,Bryson S,Carver LJ,Constantino JN,Dobkins K.Recurrence risk for autism spectrum disorders:a Baby Siblings Research Consortium study.Pediatrics 2011;128:e488-e495[PMID:21844053 DOI:10.1542/peds.2010-2825]
11 Becerra TA,von Ehrenstein OS,Heck JE,Olsen J,Arah OA,Jeste SS,Rodriguez M,Ritz B.Autism spectrum disorders and race,ethnicity,and nativity:a population-based study.Pediatrics2014;134:e63-e71[PMID:24958588 DOI:10.1542/peds.2013-3928]
12 Lavelle TA,Weinstein MC,Newhouse JP,Munir K,Kuhlthau KA,Prosser LA.Economic burden of childhood autism spectrum disorders.Pediatrics 2014;133:e520-e529[PMID:24515505 DOI:10.1542/peds.2013-0763]
13 Fakhoury M.Autistic spectrum disorders:A review of clinical features,theories and diagnosis.Int J Dev Neurosci 2015;43:70-77[PMID:25862937 DOI:10.1016/j.ijdevneu.2015.04.003]
14 Rossignol DA,Frye RE.Mitochondrial dysfunction in autism spectrum disorders:a systematic review and meta-analysis.Mol Psychiatry 2012;17:290-314[PMID:21263444 DOI:10.1038/mp.2010.136]
15 Persico AM,Bourgeron T.Searching for ways out of the autism maze:genetic,epigenetic and environmental clues.Trends Neurosci 2006;29:349-358[PMID:16808981 DOI:10.1016/j.tins.2006.05.010]
16 Rossignol DA,Bradstreet JJ.Evidence of mitochondrial dysfunction in autism and implications for treatment.Am J Biochem Biotech 2008;4:208-217[DOI:10.3844/ajbbsp.2008.208.217]
17 Gardener H,Spiegelman D,Buka SL.Perinatal and neonatal risk factors for autism:a comprehensive meta-analysis.Pediatrics 2011;128:344-355[PMID:21746727 DOI:10.1542/peds.2010-1036]
18 Durkin MS,Maenner MJ,Newschaffer CJ,Lee LC,Cunniff CM,Daniels JL,Kirby RS,Leavitt L,Miller L,Zahorodny W.Advanced parental age and the risk of autism spectrum disorder.Am JEpidemiol 2008;168:1268-1276[PMID:18945690 DOI:10.1093/aje/kwn250]
19 Ouss-Ryngaert L,Alvarez L,Boissel A.[Autism and prematurity:state of the art].Arch Pediatr2012;19:970-975[PMID:22877858 DOI:10.1016/j.arcped.2012.06.007]
20 Darcy-Mahoney A,Minter B,Higgins M,Guo Y,Williams B,Head Zauche LM,Birth K.Probability of an Autism Diagnosis by Gestational Age.Newborn Infant Nurs Rev 2016;16:322-326[PMID:28989329 DOI:10.1053/j.nainr.2016.09.019]
21 Shelton JF,Geraghty EM,Tancredi DJ,Delwiche LD,Schmidt RJ,Ritz B,Hansen RL,HertzPicciotto I.Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides:the CHARGE study.Environ Health Perspect 2014;122:1103-1109[PMID:24954055DOI:10.1289/ehp.1307044]
22 Coleman M,Blass JP.Autism and lactic acidosis.J Autism Dev Disord 1985;15:1-8[PMID:3980425 DOI:10.1007/BF01837894]
23 Lombard J.Autism:a mitochondrial disorder?Med Hypotheses 1998;50:497-500[PMID:9710323DOI:10.1016/S0306-9877(98)90270-5]
24 Loenarz C,Schofield CJ.Expanding chemical biology of 2-oxoglutarate oxygenases.Nat Chem Biol 2008;4:152-156[PMID:18277970 DOI:10.1038/nchembio0308-152]
25 Strijbis K,Vaz FM,Distel B.Enzymology of the carnitine biosynthesis pathway.IUBMB Life2010;62:357-362[PMID:20306513 DOI:10.1002/iub.323]
26 Rigault C,Le Borgne F,Demarquoy J.Genomic structure,alternative maturation and tissue expression of the human BBOX1 gene.Biochim Biophys Acta 2006;1761:1469-1481[PMID:17110165 DOI:10.1016/j.bbalip.2006.09.014]
27 Evans AM,Fornasini G.Pharmacokinetics of L-carnitine.Clin Pharmacokinet 2003;42:941-967[PMID:12908852 DOI:10.2165/00003088-200342110-00002]
28 Demarquoy J.Lcarnitine:Structure and Function.In:eLS John Wiley Sons Ltd,Chichester 2011;[DOI:10.1002/9780470015902.a0023200]
29 Bloisi W,Colombo I,Garavaglia B,Giardini R,Finocchiaro G,Didonato S.Purification and properties of carnitine acetyltransferase from human liver.Eur J Biochem 1990;189:539-546[PMID:2351134 DOI:10.1111/j.1432-1033.1990.tb15520.x]
30 Le Borgne F,Ben Mohamed A,Logerot M,Garnier E,Demarquoy J.Changes in carnitine octanoyltransferase activity induce alteration in fatty acid metabolism.Biochem Biophys Res Commun 2011;409:699-704[PMID:21619872 DOI:10.1016/j.bbrc.2011.05.068]
31 Demarquoy J,Le Borgne F.Crosstalk between mitochondria and peroxisomes.World J Biol Chem2015;6:301-309[PMID:26629313 DOI:10.4331/wjbc.v6.i4.301]
32 Pietrocola F,Galluzzi L,Bravo-San Pedro JM,Madeo F,Kroemer G.Acetyl coenzyme A:a central metabolite and second messenger.Cell Metab 2015;21:805-821[PMID:26039447 DOI:10.1016/j.cmet.2015.05.014]
33 Madiraju P,Pande SV,Prentki M,Madiraju SR.Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone acetylation.Epigenetics 2009;4:399-403[PMID:19755853 DOI:10.4161/epi.4.6.9767]
34 Le Borgne F,Ravaut G,Bernard A,Demarquoy J.L-carnitine protects C2C12 cells against mitochondrial superoxide overproduction and cell death.World J Biol Chem 2017;8:86-94[PMID:28289521 DOI:10.4331/wjbc.v8.i1.86]
35 Surai,P.F.Antioxidant action of carnitine:molecular mechanisms and practical applications.EC Veterinary Science 2015;vol.2,no 1,p.66-84
36 Rose S,Niyazov DM,Rossignol DA,Goldenthal M,Kahler SG,Frye RE.Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder.Mol Diagn Ther 2018;22:571-593[PMID:30039193 DOI:10.1007/s40291-018-0352-x]
37 Filipek PA,Juranek J,Nguyen MT,Cummings C,Gargus JJ.Relative carnitine deficiency in autism.J Autism Dev Disord 2004;34:615-623[PMID:15679182 DOI:10.1007/s10803-004-5283-1]
38 Mostafa GA,El-Gamal HA,El-Wakkad AS,El-Shorbagy OE,Hamza MM.Polyunsaturated fatty acids,carnitine and lactate as biological markers of brain energy in autistic children.Int J Child Neuropsychiatry 2005;2:179-188
39 Frye RE,Melnyk S,Macfabe DF.Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder.Transl Psychiatry 2013;3:e220[PMID:23340503 DOI:10.1038/tp.2012.143]
40 Lv QQ,You C,Zou XB,Deng HZ.Acyl-carnitine,C5DC,and C26 as potential biomarkers for diagnosis of autism spectrum disorder in children.Psychiatry Res 2018;267:277-280[PMID:29945069 DOI:10.1016/j.psychres.2018.06.027]
41 Fahmy SF,El-hamamsy MH,Zaki OK,Badary OA.l-Carnitine supplementation improves the behavioral symptoms in autistic children.Res Autism Spectr Disord 2013;7:159-66[DOI:10.1016/j.rasd.2012.07.006]
42 Celestino-Soper PB,Shaw CA,Sanders SJ,Li J,Murtha MT,Ercan-Sencicek AG,Davis L,Thomson S,Gambin T,Chinault AC.Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE.Hum Mol Genet2011;20:4360-4370[PMID:21865298 DOI:10.1093/hmg/ddr363]
43 Celestino-Soper PB,Violante S,Crawford EL,Luo R,Lionel AC,Delaby E,Cai G,Sadikovic B,Lee K,Lo C.A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism.Proc Natl Acad Sci USA 2012;109:7974-7981[PMID:22566635 DOI:10.1073/pnas.1120210109]
44 Nava C,Lamari F,Héron D,Mignot C,Rastetter A,Keren B,Cohen D,Faudet A,Bouteiller D,Gilleron M.Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes,including TMLHE.Transl Psychiatry 2012;2:e179[PMID:23092983 DOI:10.1038/tp.2012.102]
45 Ziats MN,Comeaux MS,Yang Y,Scaglia F,Elsea SH,Sun Q,Beaudet AL,Schaaf CP.Corrigendum to"Improvement of regressive autism symptoms in a child with TMLHEdeficiency following carnitine supplementation".Am J Med Genet A 2015;167A:2496[PMID:26355286 DOI:10.1002/ajmg.a.37192]
46 T?rlungeanu DC,Deliu E,Dotter CP,Kara M,Janiesch PC,Scalise M,Galluccio M,Tesulov M,Morelli E,Sonmez FM.Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.Cell 2016;167:1481-1494.e18[PMID:27912058 DOI:10.1016/j.cell.2016.11.013]
47 Medhasi S,Pinthong D,Pasomsub E,Vanwong N,Ngamsamut N,Puangpetch A,Chamnanphon M,Hongkaew Y,Pratoomwun J,Limsila P.Pharmacogenomic Study Reveals New Variants of Drug Metabolizing Enzyme and Transporter Genes Associated with SteadyState Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Thai Autism Spectrum Disorder Patients.Front Pharmacol 2016;7:475[PMID:28018217 DOI:10.3389/fphar.2016.00475]
48 Beaudet AL.Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias:A hypothesis.Bioessays 2017;39[PMID:28703319 DOI:10.1002/bies.201700012]
2 Lincoln AJ,Courchesne E,Kilman BA,Elmasian R,Allen M.A study of intellectual abilities in high-functioning people with autism.J Autism Dev Disord 1988;18:505-524[PMID:3215879 DOI:10.1007/bf02211870]
3 Baron-Cohen S,Leslie AM,Frith U.Does the autistic child have a"theory of mind"?Cognition1985;21:37-46[PMID:2934210 DOI:10.1016/0010-0277(85)90022-8]
4 HappéF,Frith U.The weak coherence account:detail-focused cognitive style in autism spectrum disorders.J Autism Dev Disord 2006;36:5-25[PMID:16450045 DOI:10.1007/s10803-005-0039-0]
5 Bogdashina O.Sensory perceptual issues in autism and asperger syndrome:different sensory experiences-different perceptual worlds.Jessica Kingsley Publishers.Jessica Kingsley Publishers,2016
6 Fombonne E.Epidemiology of pervasive developmental disorders.Pediatr Res 2009;65:591-598[PMID:19218885 DOI:10.1203/PDR.0b013e31819e7203]
7 Fombonne E.Editorial:The rising prevalence of autism.J Child Psychol Psychiatry 2018;59:717-720[PMID:29924395 DOI:10.1111/jcpp.12941]
8 Grabrucker AM.Environmental factors in autism.Front Psychiatry 2013;3:118[PMID:23346059DOI:10.3389/fpsyt.2012.00118]
9 Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006Principal Investigators;Centers for Disease Control and Prevention(CDC).Prevalence of autism spectrum disorders-Autism and Developmental Disabilities Monitoring Network,United States,2006.MMWR Surveill Summ 2009;58:1-20[PMID:20023608]
10 Ozonoff S,Young GS,Carter A,Messinger D,Yirmiya N,Zwaigenbaum L,Bryson S,Carver LJ,Constantino JN,Dobkins K.Recurrence risk for autism spectrum disorders:a Baby Siblings Research Consortium study.Pediatrics 2011;128:e488-e495[PMID:21844053 DOI:10.1542/peds.2010-2825]
11 Becerra TA,von Ehrenstein OS,Heck JE,Olsen J,Arah OA,Jeste SS,Rodriguez M,Ritz B.Autism spectrum disorders and race,ethnicity,and nativity:a population-based study.Pediatrics2014;134:e63-e71[PMID:24958588 DOI:10.1542/peds.2013-3928]
12 Lavelle TA,Weinstein MC,Newhouse JP,Munir K,Kuhlthau KA,Prosser LA.Economic burden of childhood autism spectrum disorders.Pediatrics 2014;133:e520-e529[PMID:24515505 DOI:10.1542/peds.2013-0763]
13 Fakhoury M.Autistic spectrum disorders:A review of clinical features,theories and diagnosis.Int J Dev Neurosci 2015;43:70-77[PMID:25862937 DOI:10.1016/j.ijdevneu.2015.04.003]
14 Rossignol DA,Frye RE.Mitochondrial dysfunction in autism spectrum disorders:a systematic review and meta-analysis.Mol Psychiatry 2012;17:290-314[PMID:21263444 DOI:10.1038/mp.2010.136]
15 Persico AM,Bourgeron T.Searching for ways out of the autism maze:genetic,epigenetic and environmental clues.Trends Neurosci 2006;29:349-358[PMID:16808981 DOI:10.1016/j.tins.2006.05.010]
16 Rossignol DA,Bradstreet JJ.Evidence of mitochondrial dysfunction in autism and implications for treatment.Am J Biochem Biotech 2008;4:208-217[DOI:10.3844/ajbbsp.2008.208.217]
17 Gardener H,Spiegelman D,Buka SL.Perinatal and neonatal risk factors for autism:a comprehensive meta-analysis.Pediatrics 2011;128:344-355[PMID:21746727 DOI:10.1542/peds.2010-1036]
18 Durkin MS,Maenner MJ,Newschaffer CJ,Lee LC,Cunniff CM,Daniels JL,Kirby RS,Leavitt L,Miller L,Zahorodny W.Advanced parental age and the risk of autism spectrum disorder.Am JEpidemiol 2008;168:1268-1276[PMID:18945690 DOI:10.1093/aje/kwn250]
19 Ouss-Ryngaert L,Alvarez L,Boissel A.[Autism and prematurity:state of the art].Arch Pediatr2012;19:970-975[PMID:22877858 DOI:10.1016/j.arcped.2012.06.007]
20 Darcy-Mahoney A,Minter B,Higgins M,Guo Y,Williams B,Head Zauche LM,Birth K.Probability of an Autism Diagnosis by Gestational Age.Newborn Infant Nurs Rev 2016;16:322-326[PMID:28989329 DOI:10.1053/j.nainr.2016.09.019]
21 Shelton JF,Geraghty EM,Tancredi DJ,Delwiche LD,Schmidt RJ,Ritz B,Hansen RL,HertzPicciotto I.Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides:the CHARGE study.Environ Health Perspect 2014;122:1103-1109[PMID:24954055DOI:10.1289/ehp.1307044]
22 Coleman M,Blass JP.Autism and lactic acidosis.J Autism Dev Disord 1985;15:1-8[PMID:3980425 DOI:10.1007/BF01837894]
23 Lombard J.Autism:a mitochondrial disorder?Med Hypotheses 1998;50:497-500[PMID:9710323DOI:10.1016/S0306-9877(98)90270-5]
24 Loenarz C,Schofield CJ.Expanding chemical biology of 2-oxoglutarate oxygenases.Nat Chem Biol 2008;4:152-156[PMID:18277970 DOI:10.1038/nchembio0308-152]
25 Strijbis K,Vaz FM,Distel B.Enzymology of the carnitine biosynthesis pathway.IUBMB Life2010;62:357-362[PMID:20306513 DOI:10.1002/iub.323]
26 Rigault C,Le Borgne F,Demarquoy J.Genomic structure,alternative maturation and tissue expression of the human BBOX1 gene.Biochim Biophys Acta 2006;1761:1469-1481[PMID:17110165 DOI:10.1016/j.bbalip.2006.09.014]
27 Evans AM,Fornasini G.Pharmacokinetics of L-carnitine.Clin Pharmacokinet 2003;42:941-967[PMID:12908852 DOI:10.2165/00003088-200342110-00002]
28 Demarquoy J.Lcarnitine:Structure and Function.In:eLS John Wiley Sons Ltd,Chichester 2011;[DOI:10.1002/9780470015902.a0023200]
29 Bloisi W,Colombo I,Garavaglia B,Giardini R,Finocchiaro G,Didonato S.Purification and properties of carnitine acetyltransferase from human liver.Eur J Biochem 1990;189:539-546[PMID:2351134 DOI:10.1111/j.1432-1033.1990.tb15520.x]
30 Le Borgne F,Ben Mohamed A,Logerot M,Garnier E,Demarquoy J.Changes in carnitine octanoyltransferase activity induce alteration in fatty acid metabolism.Biochem Biophys Res Commun 2011;409:699-704[PMID:21619872 DOI:10.1016/j.bbrc.2011.05.068]
31 Demarquoy J,Le Borgne F.Crosstalk between mitochondria and peroxisomes.World J Biol Chem2015;6:301-309[PMID:26629313 DOI:10.4331/wjbc.v6.i4.301]
32 Pietrocola F,Galluzzi L,Bravo-San Pedro JM,Madeo F,Kroemer G.Acetyl coenzyme A:a central metabolite and second messenger.Cell Metab 2015;21:805-821[PMID:26039447 DOI:10.1016/j.cmet.2015.05.014]
33 Madiraju P,Pande SV,Prentki M,Madiraju SR.Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone acetylation.Epigenetics 2009;4:399-403[PMID:19755853 DOI:10.4161/epi.4.6.9767]
34 Le Borgne F,Ravaut G,Bernard A,Demarquoy J.L-carnitine protects C2C12 cells against mitochondrial superoxide overproduction and cell death.World J Biol Chem 2017;8:86-94[PMID:28289521 DOI:10.4331/wjbc.v8.i1.86]
35 Surai,P.F.Antioxidant action of carnitine:molecular mechanisms and practical applications.EC Veterinary Science 2015;vol.2,no 1,p.66-84
36 Rose S,Niyazov DM,Rossignol DA,Goldenthal M,Kahler SG,Frye RE.Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder.Mol Diagn Ther 2018;22:571-593[PMID:30039193 DOI:10.1007/s40291-018-0352-x]
37 Filipek PA,Juranek J,Nguyen MT,Cummings C,Gargus JJ.Relative carnitine deficiency in autism.J Autism Dev Disord 2004;34:615-623[PMID:15679182 DOI:10.1007/s10803-004-5283-1]
38 Mostafa GA,El-Gamal HA,El-Wakkad AS,El-Shorbagy OE,Hamza MM.Polyunsaturated fatty acids,carnitine and lactate as biological markers of brain energy in autistic children.Int J Child Neuropsychiatry 2005;2:179-188
39 Frye RE,Melnyk S,Macfabe DF.Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder.Transl Psychiatry 2013;3:e220[PMID:23340503 DOI:10.1038/tp.2012.143]
40 Lv QQ,You C,Zou XB,Deng HZ.Acyl-carnitine,C5DC,and C26 as potential biomarkers for diagnosis of autism spectrum disorder in children.Psychiatry Res 2018;267:277-280[PMID:29945069 DOI:10.1016/j.psychres.2018.06.027]
41 Fahmy SF,El-hamamsy MH,Zaki OK,Badary OA.l-Carnitine supplementation improves the behavioral symptoms in autistic children.Res Autism Spectr Disord 2013;7:159-66[DOI:10.1016/j.rasd.2012.07.006]
42 Celestino-Soper PB,Shaw CA,Sanders SJ,Li J,Murtha MT,Ercan-Sencicek AG,Davis L,Thomson S,Gambin T,Chinault AC.Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE.Hum Mol Genet2011;20:4360-4370[PMID:21865298 DOI:10.1093/hmg/ddr363]
43 Celestino-Soper PB,Violante S,Crawford EL,Luo R,Lionel AC,Delaby E,Cai G,Sadikovic B,Lee K,Lo C.A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism.Proc Natl Acad Sci USA 2012;109:7974-7981[PMID:22566635 DOI:10.1073/pnas.1120210109]
44 Nava C,Lamari F,Héron D,Mignot C,Rastetter A,Keren B,Cohen D,Faudet A,Bouteiller D,Gilleron M.Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes,including TMLHE.Transl Psychiatry 2012;2:e179[PMID:23092983 DOI:10.1038/tp.2012.102]
45 Ziats MN,Comeaux MS,Yang Y,Scaglia F,Elsea SH,Sun Q,Beaudet AL,Schaaf CP.Corrigendum to"Improvement of regressive autism symptoms in a child with TMLHEdeficiency following carnitine supplementation".Am J Med Genet A 2015;167A:2496[PMID:26355286 DOI:10.1002/ajmg.a.37192]
46 T?rlungeanu DC,Deliu E,Dotter CP,Kara M,Janiesch PC,Scalise M,Galluccio M,Tesulov M,Morelli E,Sonmez FM.Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.Cell 2016;167:1481-1494.e18[PMID:27912058 DOI:10.1016/j.cell.2016.11.013]
47 Medhasi S,Pinthong D,Pasomsub E,Vanwong N,Ngamsamut N,Puangpetch A,Chamnanphon M,Hongkaew Y,Pratoomwun J,Limsila P.Pharmacogenomic Study Reveals New Variants of Drug Metabolizing Enzyme and Transporter Genes Associated with SteadyState Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Thai Autism Spectrum Disorder Patients.Front Pharmacol 2016;7:475[PMID:28018217 DOI:10.3389/fphar.2016.00475]
48 Beaudet AL.Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias:A hypothesis.Bioessays 2017;39[PMID:28703319 DOI:10.1002/bies.201700012]