{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T00:53:34Z","timestamp":1794444814152,"version":"4.9.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T00:00:00Z","timestamp":1668384000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T00:00:00Z","timestamp":1668384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"PHRC Interregional","award":["AOR13016"],"award-info":[{"award-number":["AOR13016"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Betaine is an \u201calternate\u201d methyl donor for homocysteine remethylation catalyzed by betaine homocysteine methyltransferase (BHMT), an enzyme mainly expressed in the liver and kidney. Betaine has been used for more than 30\u00a0years in pyridoxine non-responsive cystathionine beta-synthase (pnrCBS) and cobalamin C (cblC) deficiencies to lower the hyperhomocysteinemia, although little is known about the optimal therapeutic dosage and its pharmacokinetic in these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We compared 2 betaine doses (100\u00a0mg\/kg\/day vs. 250\u00a0mg\/kg\/day) in children affected by pnrCBS or cblC deficiencies. We also measured the pharmacokinetics parameters after a single dose of betaine (100 or 250\u00a0mg\/kg) in these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective, randomized, crossover clinical trial with blinded evaluation. The primary outcome was the equivalence of total plasma homocysteine (tHcy) concentrations upon one-month oral treatment with betaine at 100 versus 250\u00a0mg\/kg\/day.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven patients completed the study (5 pnrCBS and 6 cblC). tHcy concentrations were equivalent after a one-month treatment period for the two betaine dosages. Multivariate analysis showed a significant effect of betaine dose on methionine (Met) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01) and S-adenosylmethionine (SAM) concentrations (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our analysis shows that there is no overt benefit to increasing betaine dosage higher than 100\u00a0mg\/kg\/day to lower tHcy concentrations in pnrCBS and cblC deficiencies. However, increasing betaine up to 250\u00a0mg\/kg\/d could benefit cblC patients through the increase of methionine and SAM concentrations, as low Met and SAM concentrations are involved in the pathophysiology of this disease. In contrast, in pnrCBS deficiency, betaine doses higher than 100\u00a0mg\/kg\/day could be harmful to these patients with pre-existing hypermethioninemia.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                      : Clinical Trials, NCT02404337. Registered 23 May 2015\u2014prospectively registered,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\">https:\/\/clinicaltrials.gov<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-022-02567-4","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T11:20:12Z","timestamp":1668424812000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-8322","authenticated-orcid":false,"given":"Apolline","family":"Imbard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artemis","family":"Toumazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Magr\u00e9ault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Garcia-Segarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Schlemmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florentia","family":"Kaguelidou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Perronneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Haignere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne Ogier","family":"de Baulny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Kuster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Feillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Alberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Guilmin-Cr\u00e9pon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Benoist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Schiff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,14]]},"reference":[{"issue":"3","key":"2567_CR1","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1093\/ajcn\/80.3.539","volume":"80","author":"SA Craig","year":"2004","unstructured":"Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004;80(3):539\u201349.","journal-title":"Am J Clin Nutr"},{"issue":"9","key":"2567_CR2","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.clinbiochem.2010.03.009","volume":"43","author":"M Lever","year":"2010","unstructured":"Lever M, Slow S. The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clin Biochem. 2010;43(9):732\u201344.","journal-title":"Clin Biochem"},{"key":"2567_CR3","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.biochi.2020.02.012","volume":"173","author":"B Balint","year":"2020","unstructured":"Balint B, Jepchumba VK, Gueant JL, Gueant-Rodriguez RM. Mechanisms of homocysteine-induced damage to the endothelial, medial and adventitial layers of the arterial wall. Biochimie. 2020;173:100\u20136.","journal-title":"Biochimie"},{"issue":"4","key":"2567_CR4","doi-asserted-by":"publisher","first-page":"867","DOI":"10.3390\/ijms20040867","volume":"20","author":"R Esse","year":"2019","unstructured":"Esse R, Barroso M, Tavares de Almeida I, Castro R. The Contribution of Homocysteine Metabolism Disruption to Endothelial Dysfunction: State-of-the-Art. Int J Mol Sci. 2019;20(4):867.","journal-title":"Int J Mol Sci."},{"issue":"3","key":"2567_CR5","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S0166-2236(03)00032-8","volume":"26","author":"MP Mattson","year":"2003","unstructured":"Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci. 2003;26(3):137\u201346.","journal-title":"Trends Neurosci"},{"issue":"4","key":"2567_CR6","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s00726-006-0432-9","volume":"32","author":"J Perla-Kajan","year":"2007","unstructured":"Perla-Kajan J, Twardowski T, Jakubowski H. Mechanisms of homocysteine toxicity in humans. Amino Acids. 2007;32(4):561\u201372.","journal-title":"Amino Acids"},{"issue":"3","key":"2567_CR7","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/S0022-3476(81)80352-6","volume":"99","author":"LA Smolin","year":"1981","unstructured":"Smolin LA, Benevenga NJ, Berlow S. The use of betaine for the treatment of homocystinuria. J Pediatr. 1981;99(3):467\u201372.","journal-title":"J Pediatr"},{"issue":"1","key":"2567_CR8","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s10545-016-9979-0","volume":"40","author":"AA Morris","year":"2017","unstructured":"Morris AA, Kozich V, Santra S, Andria G, Ben-Omran TI, Chakrapani AB, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 2017;40(1):49\u201374.","journal-title":"J Inherit Metab Dis"},{"issue":"3","key":"2567_CR9","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1002\/jimd.12338","volume":"44","author":"V Kozich","year":"2021","unstructured":"Kozich V, Sokolova J, Morris AAM, Pavlikova M, Gleich F, Kolker S, et al. Cystathionine beta-synthase deficiency in the E-HOD registry-part I: pyridoxine responsiveness as a determinant of biochemical and clinical phenotype at diagnosis. J Inherit Metab Dis. 2021;44(3):677\u201392.","journal-title":"J Inherit Metab Dis"},{"issue":"2","key":"2567_CR10","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1097\/01.GIM.0000117334.84388.F4","volume":"6","author":"RH Singh","year":"2004","unstructured":"Singh RH, Kruger WD, Wang L, Pasquali M, Elsas LJ 2nd. Cystathionine beta-synthase deficiency: effects of betaine supplementation after methionine restriction in B6-nonresponsive homocystinuria. Genet Med. 2004;6(2):90\u20135.","journal-title":"Genet Med"},{"issue":"2","key":"2567_CR11","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1074\/jbc.275.2.1050","volume":"275","author":"S Bourot","year":"2000","unstructured":"Bourot S, Sire O, Trautwetter A, Touze T, Wu LF, Blanco C, et al. Glycine betaine-assisted protein folding in a lysA mutant of Escherichia coli. J Biol Chem. 2000;275(2):1050\u20136.","journal-title":"J Biol Chem"},{"issue":"43","key":"2567_CR12","doi-asserted-by":"publisher","first-page":"39586","DOI":"10.1074\/jbc.M103081200","volume":"276","author":"S Diamant","year":"2001","unstructured":"Diamant S, Eliahu N, Rosenthal D, Goloubinoff P. Chemical chaperones regulate molecular chaperones in vitro and in cells under combined salt and heat stresses. J Biol Chem. 2001;276(43):39586\u201391.","journal-title":"J Biol Chem"},{"issue":"1","key":"2567_CR13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s10545-010-9087-5","volume":"34","author":"J Kopecka","year":"2011","unstructured":"Kopecka J, Krijt J, Rakova K, Kozich V. Restoring assembly and activity of cystathionine beta-synthase mutants by ligands and chemical chaperones. J Inherit Metab Dis. 2011;34(1):39\u201348.","journal-title":"J Inherit Metab Dis"},{"issue":"2","key":"2567_CR14","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/BF00445602","volume":"142","author":"U Wendel","year":"1984","unstructured":"Wendel U, Bremer HJ. Betaine in the treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency. Eur J Pediatr. 1984;142(2):147\u201350.","journal-title":"Eur J Pediatr"},{"issue":"1","key":"2567_CR15","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s10545-016-9991-4","volume":"40","author":"M Huemer","year":"2017","unstructured":"Huemer M, Diodato D, Schwahn B, Schiff M, Bandeira A, Benoist JF, et al. Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency. J Inherit Metab Dis. 2017;40(1):21\u201348.","journal-title":"J Inherit Metab Dis"},{"issue":"1","key":"2567_CR16","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13023-019-1036-2","volume":"14","author":"V Valayannopoulos","year":"2019","unstructured":"Valayannopoulos V, Schiff M, Guffon N, Nadjar Y, Garcia-Cazorla A, Martinez-Pardo Casanova M, et al. Betaine anhydrous in homocystinuria: results from the RoCH registry. Orphanet J Rare Dis. 2019;14(1):66.","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"2567_CR17","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1093\/jn\/136.1.34","volume":"136","author":"U Schwab","year":"2006","unstructured":"Schwab U, Torronen A, Meririnne E, Saarinen M, Alfthan G, Aro A, et al. Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans. J Nutr. 2006;136(1):34\u20138.","journal-title":"J Nutr"},{"issue":"1","key":"2567_CR18","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1046\/j.1365-2125.2003.01717.x","volume":"55","author":"BC Schwahn","year":"2003","unstructured":"Schwahn BC, Hafner D, Hohlfeld T, Balkenhol N, Laryea MD, Wendel U. Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria. Br J Clin Pharmacol. 2003;55(1):6\u201313.","journal-title":"Br J Clin Pharmacol"},{"issue":"2","key":"2567_CR19","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1373\/49.2.286","volume":"49","author":"PI Holm","year":"2003","unstructured":"Holm PI, Ueland PM, Kvalheim G, Lien EA. Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clin Chem. 2003;49(2):286\u201394.","journal-title":"Clin Chem"},{"issue":"9","key":"2567_CR20","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1002\/pd.4142","volume":"33","author":"A Imbard","year":"2013","unstructured":"Imbard A, Blom HJ, Schlemmer D, Barto R, Czerkiewicz I, Rigal O, et al. Methylation metabolites in amniotic fluid depend on gestational age. Prenat Diagn. 2013;33(9):848\u201355.","journal-title":"Prenat Diagn"},{"issue":"8","key":"2567_CR21","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1373\/clinchem.2004.034538","volume":"50","author":"S Cognat","year":"2004","unstructured":"Cognat S, Cheillan D, Piraud M, Roos B, Jakobs C, Vianey-Saban C. Determination of guanidinoacetate and creatine in urine and plasma by liquid chromatography-tandem mass spectrometry. Clin Chem. 2004;50(8):1459\u201361.","journal-title":"Clin Chem"},{"issue":"20","key":"2567_CR22","doi-asserted-by":"publisher","first-page":"3430","DOI":"10.1002\/sim.2706","volume":"25","author":"S Senn","year":"2006","unstructured":"Senn S. Cross-over trials in statistics in medicine: the first \u201c25\u201d years. Stat Med. 2006;25(20):3430\u201342.","journal-title":"Stat Med"},{"issue":"2","key":"2567_CR23","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1046\/j.1365-2125.2002.01620.x","volume":"54","author":"A Matthews","year":"2002","unstructured":"Matthews A, Johnson TN, Rostami-Hodjegan A, Chakrapani A, Wraith JE, Moat SJ, et al. An indirect response model of homocysteine suppression by betaine: optimising the dosage regimen of betaine in homocystinuria. Br J Clin Pharmacol. 2002;54(2):140\u20136.","journal-title":"Br J Clin Pharmacol"},{"issue":"1","key":"2567_CR24","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s10545-010-9120-8","volume":"34","author":"M Schiff","year":"2011","unstructured":"Schiff M, Benoist JF, Tilea B, Royer N, Giraudier S, Ogier de Baulny H. Isolated remethylation disorders: do our treatments benefit patients? J Inherit Metab Dis. 2011;34(1):137\u201345.","journal-title":"J Inherit Metab Dis."},{"issue":"1","key":"2567_CR25","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/jmd2.12092","volume":"52","author":"BC Schwahn","year":"2020","unstructured":"Schwahn BC, Scheffner T, Stepman H, Verloo P, Das AM, Fletcher J, et al. Cystathionine beta synthase deficiency and brain edema associated with methionine excess under betaine supplementation: four new cases and a review of the evidence. JIMD Rep. 2020;52(1):3\u201310.","journal-title":"JIMD Rep"},{"issue":"1\u20132","key":"2567_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ydbio.2020.09.005","volume":"468","author":"T Chern","year":"2020","unstructured":"Chern T, Achilleos A, Tong X, Hsu CW, Wong L, Poche RA. Mouse models to study the pathophysiology of combined methylmalonic acidemia and homocystinuria, cblC type. Dev Biol. 2020;468(1\u20132):1\u201313.","journal-title":"Dev Biol"},{"issue":"3","key":"2567_CR27","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.ymgme.2014.05.002","volume":"112","author":"MA Moreno-Garcia","year":"2014","unstructured":"Moreno-Garcia MA, Pupavac M, Rosenblatt DS, Tremblay ML, Jerome-Majewska LA. The Mmachc gene is required for pre-implantation embryogenesis in the mouse. Mol Genet Metab. 2014;112(3):198\u2013204.","journal-title":"Mol Genet Metab"},{"issue":"3","key":"2567_CR28","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1212\/WNL.38.3.459","volume":"38","author":"K Hyland","year":"1988","unstructured":"Hyland K, Smith I, Bottiglieri T, Perry J, Wendel U, Clayton PT, et al. Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency. Neurology. 1988;38(3):459\u201362.","journal-title":"Neurology"},{"issue":"8782\u20138783","key":"2567_CR29","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1016\/0140-6736(91)92373-A","volume":"338","author":"R Surtees","year":"1991","unstructured":"Surtees R, Leonard J, Austin S. Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway. Lancet. 1991;338(8782\u20138783):1550\u20134.","journal-title":"Lancet"},{"key":"2567_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ymgmr.2015.02.001","volume":"3","author":"NM Jadavji","year":"2015","unstructured":"Jadavji NM, Wieske F, Dirnagl U, Winter C. Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and gamma-aminobutyric acid in brain tissue. Mol Genet Metab Rep. 2015;3:1\u20134.","journal-title":"Mol Genet Metab Rep"},{"issue":"2","key":"2567_CR31","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s00726-005-0314-6","volume":"31","author":"L Metzner","year":"2006","unstructured":"Metzner L, Neubert K, Brandsch M. Substrate specificity of the amino acid transporter PAT1. Amino Acids. 2006;31(2):111\u20137.","journal-title":"Amino Acids"},{"issue":"1","key":"2567_CR32","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/S0021-9258(18)48543-2","volume":"267","author":"A Yamauchi","year":"1992","unstructured":"Yamauchi A, Uchida S, Kwon HM, Preston AS, Robey RB, Garcia-Perez A, et al. Cloning of a Na(+)- and Cl(-)-dependent betaine transporter that is regulated by hypertonicity. J Biol Chem. 1992;267(1):649\u201352.","journal-title":"J Biol Chem"},{"issue":"1","key":"2567_CR33","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/cphy.c170041","volume":"9","author":"S Broer","year":"2018","unstructured":"Broer S, Fairweather SJ. Amino acid transport across the mammalian intestine. Compr Physiol. 2018;9(1):343\u201373.","journal-title":"Compr Physiol"},{"issue":"2","key":"2567_CR34","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/S1095-6433(00)00301-9","volume":"128","author":"H Kettunen","year":"2001","unstructured":"Kettunen H, Peuranen S, Tiihonen K, Saarinen M. Intestinal uptake of betaine in vitro and the distribution of methyl groups from betaine, choline, and methionine in the body of broiler chicks. Comp Biochem Physiol A Mol Integr Physiol. 2001;128(2):269\u201378.","journal-title":"Comp Biochem Physiol A Mol Integr Physiol"},{"issue":"4","key":"2567_CR35","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.ymgme.2007.05.002","volume":"91","author":"JM Alberto","year":"2007","unstructured":"Alberto JM, Hamelet J, Noll C, Blaise S, Bronowicki JP, Gueant JL, et al. Mice deficient in cystathionine beta synthase display altered homocysteine remethylation pathway. Mol Genet Metab. 2007;91(4):396\u20138.","journal-title":"Mol Genet Metab"},{"key":"2567_CR36","doi-asserted-by":"crossref","unstructured":"Imbard A, Benoist JF, Esse R, Gupta S, Lebon S, de Vriese AS, et al. High homocysteine induces betaine depletion. Biosci Rep. 2015;35(4).","DOI":"10.1042\/BSR20150094"},{"issue":"5","key":"2567_CR37","doi-asserted-by":"publisher","first-page":"6339","DOI":"10.1096\/fj.201802069RR","volume":"33","author":"KN Maclean","year":"2019","unstructured":"Maclean KN, Jiang H, Phinney WN, Keating AK, Hurt KJ, Stabler SP. Taurine alleviates repression of betaine-homocysteine S-methyltransferase and significantly improves the efficacy of long-term betaine treatment in a mouse model of cystathionine beta-synthase-deficient homocystinuria. FASEB J. 2019;33(5):6339\u201353.","journal-title":"FASEB J"},{"issue":"2","key":"2567_CR38","doi-asserted-by":"publisher","first-page":"252","DOI":"10.3390\/ijms18020252","volume":"18","author":"AB Ganz","year":"2017","unstructured":"Ganz AB, Cohen VV, Swersky CC, Stover J, Vitiello GA, Lovesky J, et al. Genetic variation in choline-metabolizing enzymes alters choline metabolism in young women consuming choline intakes meeting current recommendations. Int J Mol Sci. 2017;18(2):252.","journal-title":"Int J Mol Sci."},{"issue":"11","key":"2567_CR39","doi-asserted-by":"publisher","first-page":"2874","DOI":"10.1093\/jn\/nxaa266","volume":"150","author":"MN Ilozumba","year":"2020","unstructured":"Ilozumba MN, Cheng TD, Neuhouser ML, Miller JW, Beresford SAA, Duggan DJ, et al. Associations between plasma choline metabolites and genetic polymorphisms in one-carbon metabolism in postmenopausal women: the women\u2019s health initiative observational study. J Nutr. 2020;150(11):2874\u201381.","journal-title":"J Nutr"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-022-02567-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-022-02567-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-022-02567-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T11:22:48Z","timestamp":1668424968000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-022-02567-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,14]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2567"],"URL":"https:\/\/doi.org\/10.1186\/s13023-022-02567-4","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,14]]},"assertion":[{"value":"1 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration"}},{"value":"This study has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki). The protocol was approved by national ethics committees (Comit\u00e9 de Protection des Personnes [CPP IDF III], the French National Drug Safety Agency [ANSM, EudraCT 2014-003643-36] and the Franch data protection authority.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have read the final version of the manuscript and consent to the publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All of the authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"417"}}