One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders
dc.contributor.author | Paşca, Sergiu P. | en_US |
dc.contributor.author | Dronca, Eleonora | en_US |
dc.contributor.author | Kaucsár, Tamás | en_US |
dc.contributor.author | Craciun, Elena C. | en_US |
dc.contributor.author | Endreffy, Emõke | en_US |
dc.contributor.author | Ferencz, Beatrix K. | en_US |
dc.contributor.author | Iftene, Felicia | en_US |
dc.contributor.author | Benga, Ileana | en_US |
dc.contributor.author | Cornean, Rodica | en_US |
dc.contributor.author | Banerjee, Ruma | en_US |
dc.contributor.author | Dronca, Maria | en_US |
dc.date.accessioned | 2010-06-01T20:49:32Z | |
dc.date.available | 2010-06-01T20:49:32Z | |
dc.date.issued | 2009-10 | en_US |
dc.identifier.citation | Paşca, Sergiu P.; Dronca, Eleonora; KaucsÁr, TamÁs; Craciun, Elena C.; Endreffy, EmÕke; Ferencz, Beatrix K.; Iftene, Felicia; Benga, Ileana; Cornean, Rodica; Banerjee, Ruma; Dronca, Maria (2009). "One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders." Journal of Cellular and Molecular Medicine 13(10): 4229-4238. <http://hdl.handle.net/2027.42/73924> | en_US |
dc.identifier.issn | 1582-1838 | en_US |
dc.identifier.issn | 1582-4934 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/73924 | |
dc.description.abstract | Autism spectrum disorders (ASDs), which include the prototypic autistic disorder (AD), Asperger’s syndrome (AS) and pervasive developmental disorders not otherwise specified (PDD-NOS), are complex neurodevelopmental conditions of unknown aetiology. The current study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B 12 and the C677T polymorphism of the MTHFR gene in three groups of children diagnosed with AD ( n = 15), AS ( n = 5) and PDD-NOS ( n = 19) and their age- and sex-matched controls ( n = 25). No metabolic disturbances were seen in the AS patients, while in the AD and PDD-NOS groups, lower plasma levels of methionine ( P = 0.01 and P = 0.03, respectively) and Α-aminobutyrate were observed ( P = 0.01 and P = 0.001, respectively). Only in the AD group, plasma cysteine ( P = 0.02) and total blood glutathione ( P = 0.02) were found to be reduced. Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups. The serum levels of vitamin B 12 and folate were in the normal range. The results of the MTHFR gene analysis showed a normal distribution of the C677T polymorphism in children with ASDs, but the frequency of the 677T allele was slightly more prevalent in AD patients. Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs. | en_US |
dc.format.extent | 790285 bytes | |
dc.format.extent | 3109 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Blackwell Publishing Ltd | en_US |
dc.rights | © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd | en_US |
dc.subject.other | Autism | en_US |
dc.subject.other | Methionine Cycle | en_US |
dc.subject.other | Transsulphuration | en_US |
dc.subject.other | Vitamins | en_US |
dc.subject.other | MTHFR | en_US |
dc.title | One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationother | Department of Medical Biochemistry, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania | en_US |
dc.contributor.affiliationother | Center for Cognitive and Neural Studies (Coneural), Cluj-Napoca, Romania | en_US |
dc.contributor.affiliationother | Department of Genetics, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania | en_US |
dc.contributor.affiliationother | Department of Pharmaceutical Biochemistry and Clinical Laboratory, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania | en_US |
dc.contributor.affiliationother | Department of Pediatrics, Albert Szent-GyÖrgyi Medical Center, University of Szeged, Hungary | en_US |
dc.contributor.affiliationother | Molecular Biology Center, Institute of Interdisciplinary Research of Babeş-Bolyai University, Cluj-Napoca, Romania | en_US |
dc.contributor.affiliationother | Department of Child Psychiatry, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania | en_US |
dc.contributor.affiliationother | Department of Child Neurology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania | en_US |
dc.identifier.pmid | 19267885 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/73924/1/j.1582-4934.2008.00463.x.pdf | |
dc.identifier.doi | 10.1111/j.1582-4934.2008.00463.x | en_US |
dc.identifier.source | Journal of Cellular and Molecular Medicine | en_US |
dc.identifier.citedreference | Volkmar FR, Pauls D. Autism. Lancet. 2003; 362: 1133 – 41. | en_US |
dc.identifier.citedreference | 2. American Psychiatric Association. Diagnostic and Statistical Manual-Text Revision. 4th ed. Washington, DC: American Psychiatric Association; 2000. | en_US |
dc.identifier.citedreference | 3. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2002 Principal Investigators, Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders-autism and developmental disabilities monitoring network, 14 sites, United States, 2002. MMWR Surveill Summ. 2007; 56: 12 – 28. | en_US |
dc.identifier.citedreference | Baird G, Simonoff E, Pickles A, et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet. 2006; 368: 210 – 5. | en_US |
dc.identifier.citedreference | Gupta AR, State MW. Recent advances in the genetics of autism. Biol Psychiatry. 2007; 61: 429 – 37. | en_US |
dc.identifier.citedreference | Persico AM, Bourgeron T. Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci. 2006; 29: 349 – 58. | en_US |
dc.identifier.citedreference | Geschwind DH, Levitt P. Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol. 2007; 17: 103 – 11. | en_US |
dc.identifier.citedreference | Happe F, Ronald A, Plomin R. Time to give up on a single explanation for autism. Nat Neurosci. 2006; 9: 1218 – 20. | en_US |
dc.identifier.citedreference | Manzi B, Loizzo AL, Giana G, et al. Autism and metabolic diseases. J Child Neurol. 2008; 23: 307 – 14. | en_US |
dc.identifier.citedreference | James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004; 80: 1611 – 7. | en_US |
dc.identifier.citedreference | James SJ, Melnyk S, Jernigan S, et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet. 2006; 141: 947 – 56. | en_US |
dc.identifier.citedreference | PaÜsca SP, Nemes B, Vlase L, et al. High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism. Life Sci. 2006; 78: 2244 – 8. | en_US |
dc.identifier.citedreference | Geier DA, Geier MR. A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders. Horm Res. 2006; 66: 182 – 8. | en_US |
dc.identifier.citedreference | Moretti P, Peters SU, Del Gaudio D, et al. Brief report: autistic symptoms, developmental regression, mental retardation, epilepsy, and dyskinesias in CNS folate deficiency. J Autism Dev Disord. 2008; 38: 1170 – 7. | en_US |
dc.identifier.citedreference | Boris M, Goldblatt A, Galanko J, et al. Association of MTHFR gene variants with autism. J Am Phys Sur g. 2004; 9: 106 – 8. | en_US |
dc.identifier.citedreference | Deth R, Muratore C, Benzecry J, et al. How environmental and genetic factors combine to cause autism: A redox/ methylation hypothesis. Neurotoxicology. 2008; 29: 190 – 201. | en_US |
dc.identifier.citedreference | Suh J, Walsh W, McGinnis W, et al. Altered sulfur amino acid metabolism in immune cells of children diagnosed with autism. Am J Biochem Biotech. 2008; 4: 105 – 13. | en_US |
dc.identifier.citedreference | Adams M, Lucock M, Stuart J, et al. Preliminary evidence for involvement of the folate gene polymorphism 19bp deletion-DHFR in occurrence of autism. Neurosci Lett. 2007; 422: 24 – 9. | en_US |
dc.identifier.citedreference | Geier DA, Kern JK, Garver CR, et al. A prospective study of transsulfuration biomarkers in autistic disorders. Neurochem Res. 2009; 34: 394. | en_US |
dc.identifier.citedreference | Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology. 2006; 13: 171 – 81. | en_US |
dc.identifier.citedreference | Stabler SP, Lindenbaum J, Savage DG, et al. Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood. 1993; 81: 3404 – 13. | en_US |
dc.identifier.citedreference | Stabler SP, Marcell PD, Podell ER, et al. Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. J Clin Invest. 1988; 81: 466 – 74. | en_US |
dc.identifier.citedreference | Aslanidis C, Nauck M, Schmitz G. High-speed prothrombin G–>A 20210 and methylenetetrahydrofolate reductase C–>T 677 mutation detection using real-time fluorescence PCR and melting curves. Biotechniques. 1999; 27: 234 – 6, 8. | en_US |
dc.identifier.citedreference | Moore LE, Hung R, Karami S, et al. Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. Int J Cancer. 2008; 122: 1710 – 5. | en_US |
dc.identifier.citedreference | Walker DR, Thompson A, Zwaigenbaum L, et al. Specifying PDD-NOS: a comparison of PDD-NOS, Asperger syndrome, and autism. J Am Acad Child Adolesc Psychiatry. 2004; 43: 172 – 80. | en_US |
dc.identifier.citedreference | Schanen NC. Epigenetics of autism spectrum disorders. Hum Mol Genet. 2006; 2: R138 – 50. | en_US |
dc.identifier.citedreference | Sugden C. One-carbon metabolism in psychiatric illness. Nutr Res Rev. 2006; 19: 117 – 36. | en_US |
dc.identifier.citedreference | Muskiet FA, Kemperman RF. Folate and long-chain polyunsaturated fatty acids in psychiatric disease. J Nutr Biochem. 2006; 17: 717 – 27. | en_US |
dc.identifier.citedreference | Ahearn WH, Castine T, Nault K, et al. An assessment of food acceptance in children with autism or pervasive developmental disorder-not otherwise specified. J Autism Dev Disord. 2001; 31: 505 – 11. | en_US |
dc.identifier.citedreference | Arnold GL, Hyman SL, Mooney RA, et al. Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. J Autism Dev Disord. 2003; 33: 449 – 54. | en_US |
dc.identifier.citedreference | Levy SE, Souders MC, Ittenbach RF, et al. Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders. Biol Psychiatry. 2007; 61: 492 – 7. | en_US |
dc.identifier.citedreference | Rozen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb Haemost. 1997; 78: 523 – 6. | en_US |
dc.identifier.citedreference | Latif A, Heinz P, Cook R. Iron deficiency in autism and Asperger syndrome. Autism. 2002; 6: 103 – 14. | en_US |
dc.identifier.citedreference | Fernell E, Karagiannakis A, Edman G, et al. Aberrant amino acid transport in fibroblasts from children with autism. Neurosci Lett. 2007; 418: 82 – 6. | en_US |
dc.identifier.citedreference | Siva Sankar DV. Plasma levels of folates, riboflavin, vitamin B6, and ascorbate in severely disturbed children. J Autism Dev Disord. 1979; 9: 73 – 82. | en_US |
dc.identifier.citedreference | Adams JB, George F, Audhya T. Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements. J Altern Complement Med. 2006; 12: 59 – 63. | en_US |
dc.identifier.citedreference | Adams JB, Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med. 2004; 10: 1033 – 9. | en_US |
dc.identifier.citedreference | Geier DA, Geier MR. A prospective assessment of androgen levels in patients with autistic spectrum disorders: biochemical underpinnings and suggested therapies. Neuro Endocrinol Lett. 2007; 28: 565 – 73. | en_US |
dc.identifier.citedreference | Prudova A, Albin M, Bauman Z, et al. Testosterone regulation of homocysteine metabolism modulates redox status in human prostate cancer cells. Antioxid Redox Signal. 2007; 9: 1875 – 81. | en_US |
dc.identifier.citedreference | Vitvitsky V, Prudova A, Stabler S, et al. Testosterone regulation of renal cystathionine beta-synthase: implications for sex-dependent differences in plasma homocysteine levels. Am J Physiol Renal Physiol. 2007; 293: F594 – 600. | en_US |
dc.identifier.citedreference | Alberti A, Pirrone P, Elia M, et al. Sulphation deficit in “low-functioning” autistic children: a pilot study. Biol Psychiatry. 1999; 46: 420 – 4. | en_US |
dc.identifier.citedreference | Clarkson TW, Nordberg GF, Sager PR. Reproductive and developmental toxicity of metals. Scand J Work Environ Health. 1985; 11: 145 – 54. | en_US |
dc.identifier.citedreference | Nataf R, Skorupka C, Amet L, et al. Porphyrinuria in childhood autistic disorder: implications for environmental toxicity. Toxicol Appl Pharmacol. 2006; 214: 99 – 108. | en_US |
dc.identifier.citedreference | Geier DA, Geier MR. A prospective study of mercury toxicity biomarkers in autistic spectrum disorders. J Toxicol Environ Health A. 2007; 70: 1723 – 30. | en_US |
dc.identifier.citedreference | Geier DA, Geier MR. A prospective assessment of porphyrins in autistic disorders: a potential marker for heavy metal exposure. Neurotox Res. 2006; 10: 57 – 64. | en_US |
dc.identifier.citedreference | Boger-Megiddo I, Shaw DW, Friedman SD, et al. Corpus callosum morphometrics in young children with autism spectrum disorder. J Autism Dev Disord. 2006; 36: 733 – 9. | en_US |
dc.identifier.citedreference | Connolly AM, Chez M, Streif EM, et al. Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy. Biol Psychiatry. 2006; 59: 354 – 63. | en_US |
dc.identifier.citedreference | Van den Veyver IB. Genetic effects of methylation diets. Annu Rev Nutr. 2002; 22: 255 – 82. | en_US |
dc.identifier.citedreference | Badcock C, Crespi B. Imbalanced genomic imprinting in brain development: an evolutionary basis for the aetiology of autism. J Evol Biol. 2006; 19: 1007 – 32. | en_US |
dc.identifier.citedreference | Uhlhaas PJ, Singer W. What do disturbances in neural synchrony tell us about autism ? Biol Psychiatry. 2007; 62: 190 – 1. | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.