{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:08:51Z","timestamp":1783685331955,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T00:00:00Z","timestamp":1360281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rett syndrome is a neurodevelopmental disorder characterized by cognitive and locomotor regression and stereotypic hand movements. The disorder is caused by mutations in the X chromosomal MECP2 a gene encoding methyl CpG\u2010binding protein. It has been associated with disturbances of cerebral folate homeostasis, as well as with speculations on a compromised DNA\u2010methylation. Folinic acid is the stable form of folate. Its derived intermediate 5\u2010MTHF supports the conversion of homocysteine to methionine, the precursor of S\u2010adenosylmethionine (SAM). This in turn donates its methyl group to various acceptors, including DNA, thereby being converted to S\u2010adenosylhomocysteine (SAH). The SAM\/SAH ratio reflects the methylation potential. The goal of our study was to influence DNA methylation processes and ameliorate the clinical symptoms in Rett syndrome. Therefore we examined the hypothesis that folinic acid supplementation, besides increasing cerebrospinal fluid (CSF) 5\u2010MTHF (<jats:italic>p<\/jats:italic>\u2009=\u20090.003), influences SAM and SAH and their ratio. In our randomized, double\u2010blind crossover study on folinic acid supplementation, ten female Rett patients received both folinic acid and placebo for 1 year each. It was shown that both SAM and SAH levels in the CSF remained unchanged following folinic acid administration (<jats:italic>p<\/jats:italic>\u2009=\u20090.202 and <jats:italic>p<\/jats:italic>\u2009=\u20090.097, respectively) in spite of a rise of plasma SAM and SAH (<jats:italic>p<\/jats:italic>\u2009=\u20090.007; <jats:italic>p<\/jats:italic>\u2009=\u20090.009). There was no significant change in the SAM\/SAH ratio either in plasma or CSF. The apparent inability of Rett patients to upregulate SAM and SAH levels in the CSF may contribute to the biochemical anomalies of the Rett syndrome. Our studies warrant further attempts to promote DNA methylation in the true region of interest, i.e. the brain.<\/jats:p>","DOI":"10.1007\/s10545-013-9590-6","type":"journal-article","created":{"date-parts":[[2013,2,7]],"date-time":"2013-02-07T14:15:45Z","timestamp":1360246545000},"page":"967-972","source":"Crossref","is-referenced-by-count":14,"title":["S\u2010adenosylmethionine and S\u2010adenosylhomocysteine in plasma and cerebrospinal fluid in Rett syndrome and the effect of folinic acid supplementation"],"prefix":"10.1002","volume":"36","author":[{"given":"Eveline E. O.","family":"Hagebeuk","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology Academic Medical Center PO Box 22660 Amsterdam 1000 AZ The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinus","family":"Duran","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases Clinical Biochemical Geneticist, Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico G. G. M.","family":"Abeling","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases Clinical Biochemical Geneticist, Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno","family":"Vyth","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bwee Tien","family":"Poll\u2010The","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Academic Medical Center PO Box 22660 Amsterdam 1000 AZ The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.53.12.1096"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199448020-00002"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114599001221"},{"issue":"7","key":"e_1_2_8_5_1","first-page":"S53","article-title":"Low\u2010Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial","volume":"52","author":"Brouwer IA","year":"2000","journal-title":"Indian Heart J"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)02654-9"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-76698-8_5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-76698-8_6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0b013e31822177a8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073808327827"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-007-0500-9"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/ejpn.2002.0612"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073810390037"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073811417184"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2007.310"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2008.05.018"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2001.5421"},{"issue":"2","key":"e_1_2_8_18_1","first-page":"845","article-title":"Influence of oral S\u2010adenosylmethionine on plasma 5\u2010methyltetrahydrofolate, S\u2010adenosyl\u2010homocysteine, homocysteine and methionine in healthy humans","volume":"282","author":"Loehrer FM","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000165342"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000291011.54508.aa"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2006.076448"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-873078"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2004.tb00451.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000078939.64774.1B"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2012-0056"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92373-A"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2008.05.003"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-013-9590-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T07:36:19Z","timestamp":1694763379000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-013-9590-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,8]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1007\/s10545-013-9590-6"],"URL":"https:\/\/doi.org\/10.1007\/s10545-013-9590-6","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,8]]}}}