{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:29Z","timestamp":1787029049390,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:00Z","timestamp":1582243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, the levels of concentration of homocysteine thiolactone (HTL), cysteine (Cys), and cysteinylglycine (CysGly) in the urine of autistic and non-autistic children were investigated and compared. HTL has never been analyzed in autistic children. The levels of low molecular weight sulfur compounds in the urine of both groups were determined by validated methods based on high-performance liquid chromatography with spectrofluorometric and diode-array detectors. The statistical data show a significant difference between the examined groups. Children with autism were characterized by a significantly higher level of HTL (p = 5.86 \u00d7 10\u22128), Cys (p = 1.49 \u00d7 10\u221210) and CysGly (p = 1.06 \u00d7 10\u22128) in urine compared with the control group. A difference in the p-value of &lt;0.05 is statistically significant. Higher levels of HTL, Cys, and CysGly in the urine of 41 children with autism, aged 3 to 17, were observed. The obtained results may indicate disturbances in the metabolism of methionine, Cys, and glutathione in some autistic patients. These preliminary results suggest that further research with more rigorous designs and a large number of subjects is needed.<\/jats:p>","DOI":"10.3390\/molecules25040973","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T03:21:16Z","timestamp":1582773676000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Higher Levels of Low Molecular Weight Sulfur Compounds and Homocysteine Thiolactone in the Urine of Autistic Children"],"prefix":"10.3390","volume":"25","author":[{"given":"Paulina","family":"G\u0105tarek","sequence":"first","affiliation":[{"name":"Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-5502","authenticated-orcid":false,"given":"Angelina","family":"Rosiak","sequence":"additional","affiliation":[{"name":"Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8737-7913","authenticated-orcid":false,"given":"Kamila","family":"Borowczyk","sequence":"additional","affiliation":[{"name":"Department of Environmental Chemistry, Faculty of Chemistry, University of Lodz, 91-403 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0071-1470","authenticated-orcid":false,"given":"Rafa\u0142","family":"G\u0142owacki","sequence":"additional","affiliation":[{"name":"Department of Environmental Chemistry, Faculty of Chemistry, University of Lodz, 91-403 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5106-4667","authenticated-orcid":false,"given":"Joanna","family":"Ka\u0142u\u017cna-Czapli\u0144ska","sequence":"additional","affiliation":[{"name":"Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5), American Psychiatric Association Publishing. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.clinbiochem.2011.01.015","article-title":"Noninvasive urinary organic acids test to assess biochemical and nutritional individuality in autistic children","volume":"44","year":"2011","journal-title":"Clin. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jpba.2018.01.007","article-title":"Identification of metabolic pathway disturbances using multimodal metabolomics in autistic disorders in a Middle Eastern population","volume":"152","author":"Bitar","year":"2018","journal-title":"J. Pharmaceut. Biomed."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s00213-013-3290-7","article-title":"Biomarkers in autism spectrum disorder: The old and the new","volume":"231","author":"Ruggeri","year":"2014","journal-title":"Psychopharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00726-016-2332-y","article-title":"Body fluid levels of neuroactive amino acids in autism spectrum disorders: A review of the literature","volume":"49","author":"Zheng","year":"2017","journal-title":"Amino Acids"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.trac.2015.04.029","article-title":"Analysis of amino acids in autism spectrum disorders","volume":"73","year":"2015","journal-title":"TRAC Trends Anal. Chem."},{"key":"ref_7","first-page":"31","article-title":"Homocysteine level in urine of autistic and healthy children","volume":"58","author":"Michalska","year":"2011","journal-title":"Acta Biochim. Pol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1046\/j.1523-1755.2002.00151.x","article-title":"Plasma aminothiol oxidation in chronic hemodialysis patients","volume":"61","author":"Himmelfarb","year":"2002","journal-title":"Kidney Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0006-2952(00)00293-8","article-title":"Status of glutathione and other thiols and disulfides in human plasma","volume":"60","author":"Kleinman","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1096\/fj.06-7435com","article-title":"Mutations in methylenetetrahydrofolate reductase or cystathionine \u03b2-synthase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice","volume":"21","author":"Chwatko","year":"2007","journal-title":"FASEB J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1007\/s12325-008-0097-8","article-title":"Plasma homocysteine thiolactone associated with risk of macrovasculopathy in Chinese patients with type 2 diabetes mellitus","volume":"25","author":"Gu","year":"2008","journal-title":"Adv. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/joim.12834","article-title":"Urinary excretion of homocysteine thiolactone and the risk of acute myocardial infarction in coronary artery disease patients: The WENBIT trial","volume":"285","author":"Borowczyk","year":"2019","journal-title":"J. Int. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.yebeh.2014.08.134","article-title":"Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder","volume":"47","author":"Frye","year":"2015","journal-title":"Epilepsy Behav."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fnmol.2017.00034","article-title":"Metabolic Dysfunction Underlying Autism Spectrum Disorder and Potential Treatment Approaches","volume":"10","author":"Cheng","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5923","DOI":"10.1073\/pnas.94.11.5923","article-title":"Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor","volume":"94","author":"Lipton","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6920","DOI":"10.1523\/JNEUROSCI.20-18-06920.2000","article-title":"Homocysteine elicits a DNA damage response in neurons that promotesapoptosis and hypersensitivity to excitotoxicity","volume":"20","author":"Kruman","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jchromb.2014.12.032","article-title":"Simultaneous determination of albumin and low-molecular-mass thiols in plasma by HPLC with UV detection","volume":"981\u2013982","author":"Borowczyk","year":"2015","journal-title":"J. Chromatogr. B"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00216-005-3166-8","article-title":"Determination of total cysteamine in human plasma in the form of its 2-S-quinolinium derivative by high performance liquid chromatography","volume":"382","author":"Bald","year":"2005","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00726-010-0521-7","article-title":"An on-column derivatization method for the determination of homocysteine-thiolactone and protein N-linked homocysteine","volume":"41","author":"Bald","year":"2011","journal-title":"Amino Acids."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jchromb.2014.04.051","article-title":"Determination of homocysteine thiolactone in urine by field amplified sample injection and sweeping MEKC method with UV detection","volume":"961","author":"Furmaniak","year":"2014","journal-title":"J. Chromatogr. B"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jchromb.2018.09.009","article-title":"Application of GC-MS technique for the determination of homocysteine thiolactone in human urine","volume":"1099","author":"Chwatko","year":"2018","journal-title":"J. Chromatogr. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1016\/S0021-9258(19)67504-6","article-title":"Metabolism of homocysteine thiolactone in human cell cultures: Possible mechanism for pathological consequences of elevated homocysteine levels","volume":"272","author":"Jakubowski","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D801","DOI":"10.1093\/nar\/gks1065","article-title":"HMDB 3.0\u2013The Human Metabolome Database in 2013","volume":"41","author":"Wishart","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.biopha.2003.11.005","article-title":"Sulfur containing amino acids and human disease","volume":"58","author":"Townsend","year":"2004","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1556\/AChrom.21.2009.3.5","article-title":"Analysis of major urinary aminothiols by high-performance liquid chromatography with ultraviolet detection","volume":"21","author":"Bald","year":"2009","journal-title":"Acta Chromatogr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1152\/physrev.1970.50.3.428","article-title":"Effects of ingestion of disproportionate amounts of amino acids","volume":"50","author":"Harper","year":"1970","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev.nu.04.070184.001105","article-title":"Adverse effects of excessive consumption of amino acids","volume":"4","author":"Benevenga","year":"1984","journal-title":"Annu. Rev. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1093\/jn\/118.1.128","article-title":"Effects of ingestion of high protein or excess methionine diets by rats for two years","volume":"118","author":"Fau","year":"1988","journal-title":"J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1155\/2013\/536521","article-title":"Increased glutamate and homocysteine and decreasedglutamine levels in autism: A review and strategies for future studies of aminoacids in autism","volume":"35","author":"Ghanizadeh","year":"2013","journal-title":"Dis. Markers"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1093\/ajcn\/80.6.1611","article-title":"Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism","volume":"80","author":"James","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1016\/j.lfs.2005.09.040","article-title":"High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism","volume":"78","author":"Pasca","year":"2006","journal-title":"Life Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.nutres.2011.03.009","article-title":"Vitamin supplementation reduces the level of homocysteine in the urine of autistic children","volume":"31","author":"Michalska","year":"2011","journal-title":"Nutr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10882-005-4387-7","article-title":"Comparing selective eaters with and without developmental disabilities","volume":"17","author":"Williams","year":"2005","journal-title":"J. Dev. Phys. Disabil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1089\/acm.2004.10.1033","article-title":"Pilot study of a moderate dose multivitamin\/mineral supplement for children with autistic spectrum disorder","volume":"10","author":"Adams","year":"2004","journal-title":"J. Altern. Complem. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1089\/acm.2010.0146","article-title":"Effectiveness of nutritional supplements for reducing symptoms in autism- spectrum disorder: A case report","volume":"17","author":"Xia","year":"2011","journal-title":"J. Altern. Complem. Med."},{"key":"ref_36","first-page":"137","article-title":"A focus on homocysteine in autism","volume":"60","author":"Michalska","year":"2013","journal-title":"Acta Biochim. Pol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ijdevneu.2015.06.006","article-title":"Abnormal transsulfuration metabolism and reduced antioxidant capacity in Chinese children with autism spectrum disorders","volume":"46","author":"Han","year":"2015","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1096\/fasebj.13.15.2277","article-title":"Protein homocysteinylation: Possible mechanism underlying pathological consequences of elevated homocysteine levels","volume":"13","author":"Jakubowski","year":"1999","journal-title":"FASEB J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"377S","DOI":"10.1093\/jn\/130.2.377S","article-title":"Homocysteine thiolactone: Metabolic origin and protein homocysteinylation in humans","volume":"130","author":"Jakubowski","year":"2000","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1373\/clinchem.2004.042531","article-title":"Urinary excretion of homocysteine-thiolactone in humans","volume":"51","author":"Chwatko","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Filip, N., and Iancu, C.-E. (2018). HPLC analysis of homocysteine and related compounds, non-proteinogenic amino acids. Non-Proteinogenic Amino Acids, IntechOpen Limited.","DOI":"10.5772\/intechopen.71648"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1741S","DOI":"10.1093\/jn\/136.6.1741S","article-title":"Pathophysiological consequences of homocysteine excess","volume":"136","author":"Jakubowski","year":"2006","journal-title":"J. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1086\/513520","article-title":"The methylenetetrahydrofolate reductase 677C\u2192T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism","volume":"80","author":"Hustad","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.neulet.2007.05.025","article-title":"Preliminary evidence for involvement of folate gene polymorphism 19bp deletion-DHFR in occurrence of autism","volume":"422","author":"Adams","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1002\/ajmg.b.31094","article-title":"A functional polymorphism in the reduced folate carrier gene and DANN hypomethylation in mothers of children with autism","volume":"153B","author":"James","year":"2010","journal-title":"Am. J. Med. Genet. B"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1055\/s-2002-37082","article-title":"Psychomotor retardation, spastic paraplegia, cerebellar ataxia, and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: A novel neurometabolic condition responding to folinic acid substitution","volume":"33","author":"Ramaekers","year":"2002","journal-title":"Neuropediatrics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1097\/EDE.0b013e31821d0e30","article-title":"Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism","volume":"22","author":"Schmidt","year":"2011","journal-title":"Epidemiology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1742-4682-5-8","article-title":"A mathematical model of glutathione metabolism","volume":"5","author":"Reed","year":"2008","journal-title":"Theor. Biol. Med. Model."},{"key":"ref_49","first-page":"472","article-title":"Autism, an extreme challenge to integrative medicine. Part II: Medical management","volume":"7","author":"Kidd","year":"2002","journal-title":"Altern. Med. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.aca.2010.09.023","article-title":"Speciation and determination of thiols in biological samples using high performance liquid chromatography-inductively coupled plasma-mass spectrometry and high performance liquid chromatography-Orbitrap MS","volume":"680","author":"Bakirdere","year":"2010","journal-title":"Anal. Chim. Acta"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s42003-019-0485-4","article-title":"Metabolome signature of autism in the human prefrontal cortex","volume":"2","author":"Kurochkin","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1021\/pr901188e","article-title":"Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls","volume":"9","author":"Yap","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S0006-3223(98)00337-0","article-title":"Sulphation deficit in \u2018low functioning\u2019 autistic children: A pilot study","volume":"46","author":"Alberti","year":"1999","journal-title":"Biol. Psychiat."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3945\/ajcn.2008.26615","article-title":"Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism","volume":"89","author":"James","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_55","unstructured":"World Health Organization (2003). The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research, World Health Organization."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1093\/clinchem\/38.10.1933","article-title":"Serum creatinine as an index of renal function: New insights into old concepts","volume":"38","author":"Perrone","year":"1992","journal-title":"Clin. Chem."},{"key":"ref_57","first-page":"427","article-title":"Studies of urea excretion. II. Relationship between urine volume and the rate of urea excretion by normal adults","volume":"6","author":"Moller","year":"1928","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1515\/cclm.1991.29.3.185","article-title":"Urine screening in outdoor volunteers: Day versus night versus 24 h collection","volume":"29","author":"Khalaf","year":"1991","journal-title":"Clin. Chem. Lab Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1093\/clinchem\/37.6.785","article-title":"The role of the laboratory in evaluation of kidney function","volume":"37","author":"Cohen","year":"1991","journal-title":"Clin. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00216-006-0454-x","article-title":"Analysis of urine for cysteine, cysteinylglycine, and homocysteine by high-performance liquid chromatography","volume":"385","author":"Bald","year":"2006","journal-title":"Anal. Bioanal. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/4\/973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:59:45Z","timestamp":1760173185000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/4\/973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,21]]},"references-count":60,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["molecules25040973"],"URL":"https:\/\/doi.org\/10.3390\/molecules25040973","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,21]]}}}