{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:49:18Z","timestamp":1792097358116,"version":"4.4.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"DOI":"10.1007\/s00431-026-07519-9","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:39:03Z","timestamp":1792096743000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic timing in cerebral creatine deficiency syndromes: neurodevelopmental and genetic characterization of a multicenter cohort"],"prefix":"10.1007","volume":"185","author":[{"given":"Mehmet Akif","family":"Kilic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8777-3548","authenticated-orcid":false,"given":"Volkan","family":"Karaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3223-5408","authenticated-orcid":false,"given":"Pinar","family":"Gencpinar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1821-6881","authenticated-orcid":false,"given":"Ayfer","family":"Sakarya Gunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6304-9800","authenticated-orcid":false,"given":"Fatma Mujgan","family":"Sonmez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7994-4394","authenticated-orcid":false,"given":"Halil Ibrahim","family":"Aydin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-5267","authenticated-orcid":false,"given":"Olgay","family":"Bildik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safiye Gunes","family":"Sager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0596-2690","authenticated-orcid":false,"given":"Tugce","family":"Aksu Uzunhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-6297","authenticated-orcid":false,"given":"Cagatay","family":"Gunay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9414-2231","authenticated-orcid":false,"given":"Ozlem","family":"Ates Yaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-8193","authenticated-orcid":false,"given":"Hakan","family":"Ercelebi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5887-6468","authenticated-orcid":false,"given":"Gunce","family":"Basarir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Gok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melike","family":"Ersoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9297-8222","authenticated-orcid":false,"given":"Deniz","family":"Sunnetci Akkoyunlu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza","family":"Polat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9647-8970","authenticated-orcid":false,"given":"Ayberk","family":"Turkyilmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Turan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1714-3740","authenticated-orcid":false,"given":"Bulent","family":"Uyanik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhtesem","family":"Agildere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-7634","authenticated-orcid":false,"given":"Hande","family":"Kaymakcalan Celebiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1206-6010","authenticated-orcid":false,"given":"Muhammed","family":"Mehtar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5902-3501","authenticated-orcid":false,"given":"Nihal","family":"Olgac Dundar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8016-0404","authenticated-orcid":false,"given":"Edibe","family":"Pembegul Yildiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bulent","family":"Kara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8869-0277","authenticated-orcid":false,"given":"Hulya","family":"Maras Genc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"7519_CR1","unstructured":"Mercimek-Andrews S, Salomons GS 2009 Jan 15 [Updated 2025 Aug 7]. Creatine deficiency disorders. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132026. https:\/\/www.ncbi.nlm.nih.gov\/books\/"},{"key":"7519_CR2","doi-asserted-by":"publisher","first-page":"129","DOI":"10.5152\/TurkArchPediatr.2023.23022","volume":"58","author":"C Mulik","year":"2023","unstructured":"Mulik C, Mercimek-Andrews S (2023) Creatine deficiency disorders: phenotypes, genotypes, diagnosis, and treatment outcomes. Turk Arch Pediatr 58:129\u2013135. https:\/\/doi.org\/10.5152\/TurkArchPediatr.2023.23022","journal-title":"Turk Arch Pediatr"},{"key":"7519_CR3","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1007\/s00438-015-1067-x","volume":"290","author":"CL Desroches","year":"2015","unstructured":"Desroches CL, Patel J, Wang P, Minassian B, Marshall CR, Salomons GS, Mercimek-Mahmutoglu S (2015) Carrier frequency of guanidinoacetate methyltransferase deficiency in the general population by functional characterization of missense variants in the GAMT gene. Mol Genet Genomics 290:2163\u20132171. https:\/\/doi.org\/10.1007\/s00438-015-1067-x","journal-title":"Mol Genet Genomics"},{"key":"7519_CR4","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.gene.2015.08.045","volume":"575","author":"S Mercimek-Mahmutoglu","year":"2016","unstructured":"Mercimek-Mahmutoglu S, Pop A, Kanhai W, Fernandez Ojeda M, Holwerda U, Smith D, Loeber JG, Schielen PC, Salomons GS (2016) A pilot study to estimate incidence of guanidinoacetate methyltransferase deficiency in newborns by direct sequencing of the GAMT gene. Gene 575:127\u2013131. https:\/\/doi.org\/10.1016\/j.gene.2015.08.045","journal-title":"Gene"},{"key":"7519_CR5","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1002\/humu.23018","volume":"37","author":"CL DesRoches","year":"2016","unstructured":"DesRoches CL, Bruun T, Wang P, Marshall CR, Mercimek-Mahmutoglu S (2016) Arginine-glycine amidinotransferase deficiency and functional characterization of missense variants in GATM. Hum Mutat 37:926\u2013932. https:\/\/doi.org\/10.1002\/humu.23018","journal-title":"Hum Mutat"},{"key":"7519_CR6","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s10545-014-9713-8","volume":"37","author":"JM van de Kamp","year":"2014","unstructured":"van de Kamp JM, Mancini GM, Salomons GS (2014) X-linked creatine transporter deficiency: clinical aspects and pathophysiology. J Inherit Metab Dis 37:715\u2013733. https:\/\/doi.org\/10.1007\/s10545-014-9713-8","journal-title":"J Inherit Metab Dis"},{"key":"7519_CR7","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1186\/s13023-020-01617-z","volume":"15","author":"S Bahl","year":"2020","unstructured":"Bahl S, Cordeiro D, MacNeil L, Schulze A, Mercimek-Andrews S (2020) Urine creatine metabolite panel as a screening test in neurodevelopmental disorders. Orphanet J Rare Dis 15:339. https:\/\/doi.org\/10.1186\/s13023-020-01617-z","journal-title":"Orphanet J Rare Dis"},{"key":"7519_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40348-024-00188-4","volume":"12","author":"C Kaufman","year":"2025","unstructured":"Kaufman C, D\u2019Andrea A, Hackenberg A, Poms M, Braissant O, Haberle J (2025) Diagnostic delay in cerebral creatine deficiency disorders: lessons learned from a cross-sectional single center study, and guanidinoacetate and creatine measurements in Switzerland between 2015 and 2023. Mol Cell Pediatr 12:1. https:\/\/doi.org\/10.1186\/s40348-024-00188-4","journal-title":"Mol Cell Pediatr"},{"key":"7519_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-96","volume":"7","author":"D Cheillan","year":"2012","unstructured":"Cheillan D, Joncquel-Chevalier Curt M, Briand G, Salomons GS, Mention-Mulliez K, Dobbelaere D, Cuisset JM, Lion-Francois L, Portes VD, Chabli A et al (2012) Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms. Orphanet J Rare Dis 7:96. https:\/\/doi.org\/10.1186\/1750-1172-7-96","journal-title":"Orphanet J Rare Dis"},{"key":"7519_CR10","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ymgme.2013.10.018","volume":"111","author":"S Stockler-Ipsiroglu","year":"2014","unstructured":"Stockler-Ipsiroglu S, van Karnebeek C, Longo N, Korenke GC, Mercimek-Mahmutoglu S, Marquart I, Barshop B, Grolik C, Schlune A, Angle B et al (2014) Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring. Mol Genet Metab 111:16\u201325. https:\/\/doi.org\/10.1016\/j.ymgme.2013.10.018","journal-title":"Mol Genet Metab"},{"key":"7519_CR11","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.ymgme.2015.10.003","volume":"116","author":"S Stockler-Ipsiroglu","year":"2015","unstructured":"Stockler-Ipsiroglu S, Apatean D, Battini R, DeBrosse S, Dessoffy K, Edvardson S, Eichler F, Johnston K, Koeller DM, Nouioua S et al (2015) Arginine:glycine amidinotransferase (AGAT) deficiency: clinical features and long term outcomes in 16 patients diagnosed worldwide. Mol Genet Metab 116:252\u2013259. https:\/\/doi.org\/10.1016\/j.ymgme.2015.10.003","journal-title":"Mol Genet Metab"},{"key":"7519_CR12","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.ymgme.2010.08.016","volume":"101","author":"S Mercimek-Mahmutoglu","year":"2010","unstructured":"Mercimek-Mahmutoglu S, Connolly MB, Poskitt KJ, Horvath GA, Lowry N, Salomons GS, Casey B, Sinclair G, Davis C, Jakobs C, Stockler-Ipsiroglu S (2010) Treatment of intractable epilepsy in a female with SLC6A8 deficiency. Mol Genet Metab 101:409\u2013412. https:\/\/doi.org\/10.1016\/j.ymgme.2010.08.016","journal-title":"Mol Genet Metab"},{"key":"7519_CR13","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s10545-011-9358-9","volume":"35","author":"V Valayannopoulos","year":"2012","unstructured":"Valayannopoulos V, Boddaert N, Chabli A, Barbier V, Desguerre I, Philippe A, Afenjar A, Mazzuca M, Cheillan D, Munnich A et al (2012) Treatment by oral creatine, L-arginine and L-glycine in six severely affected patients with creatine transporter defect. J Inherit Metab Dis 35:151\u2013157. https:\/\/doi.org\/10.1007\/s10545-011-9358-9","journal-title":"J Inherit Metab Dis"},{"key":"7519_CR14","doi-asserted-by":"publisher","unstructured":"van de Kamp JM, Pouwels PJ, Aarsen FK, ten Hoopen LW, Knol DL, de Klerk JB, de Coo IF, Huijmans JG, Jakobs C, van der Knaap MS et al (2012) Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect. J Inherit Metab Dis 35:141\u2013149. https:\/\/doi.org\/10.1007\/s10545-011-9345-1","DOI":"10.1007\/s10545-011-9345-1"},{"key":"7519_CR15","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1007\/s11011-018-0197-3","volume":"33","author":"TUJ Bruun","year":"2018","unstructured":"Bruun TUJ, Sidky S, Bandeira AO, Debray FG, Ficicioglu C, Goldstein J, Joost K, Koeberl DD, Luisa D, Nassogne MC et al (2018) Treatment outcome of creatine transporter deficiency: international retrospective cohort study. Metab Brain Dis 33:875\u2013884. https:\/\/doi.org\/10.1007\/s11011-018-0197-3","journal-title":"Metab Brain Dis"},{"key":"7519_CR16","doi-asserted-by":"publisher","unstructured":"Group\u00a0WHO Multicentre Growth Reference Study Group (2006) WHO Motor Development Study: windows of achievement for six gross motor development milestones. Acta Paediatr Suppl 450:86\u201395. https:\/\/doi.org\/10.1111\/j.1651-2227.2006.tb02379.x","DOI":"10.1111\/j.1651-2227.2006.tb02379.x"},{"key":"7519_CR17","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1111\/epi.12550","volume":"55","author":"RS Fisher","year":"2014","unstructured":"Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr., Forsgren L, French JA, Glynn M et al (2014) ILAE official report: a practical clinical definition of epilepsy. Epilepsia 55:475\u2013482. https:\/\/doi.org\/10.1111\/epi.12550","journal-title":"Epilepsia"},{"key":"7519_CR18","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1111\/j.1528-1167.2009.02397.x","volume":"51","author":"P Kwan","year":"2010","unstructured":"Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G, Moshe SL, Perucca E, Wiebe S, French J (2010) Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51:1069\u20131077. https:\/\/doi.org\/10.1111\/j.1528-1167.2009.02397.x","journal-title":"Epilepsia"},{"key":"7519_CR19","doi-asserted-by":"publisher","unstructured":"American Psychiatric Association (2022) Diagnostic and statistical manual of mental disorders. American Psychiatric Association Publishing. https:\/\/doi.org\/10.1176\/appi.books.9780890425787","DOI":"10.1176\/appi.books.9780890425787"},{"key":"7519_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108362","volume":"142","author":"J Goldstein","year":"2024","unstructured":"Goldstein J, Thomas-Wilson A, Groopman E, Aggarwal V, Bianconi S, Fernandez R, Hart K, Longo N, Liang N, Reich D et al (2024) ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes. Mol Genet Metab 142:108362. https:\/\/doi.org\/10.1016\/j.ymgme.2024.108362","journal-title":"Mol Genet Metab"},{"key":"7519_CR21","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405\u2013424. https:\/\/doi.org\/10.1038\/gim.2015.30","journal-title":"Genet Med"},{"key":"7519_CR22","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1023\/A:1026764703486","volume":"23","author":"NM Verhoeven","year":"2000","unstructured":"Verhoeven NM, Guerand WS, Struys EA, Bouman AA, van der Knaap MS, Jakobs C (2000) Plasma creatinine assessment in creatine deficiency: a diagnostic pitfall. J Inherit Metab Dis 23:835\u2013840. https:\/\/doi.org\/10.1023\/A:1026764703486","journal-title":"J Inherit Metab Dis"},{"key":"7519_CR23","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2025-072219","author":"LH Rodan","year":"2025","unstructured":"Rodan LH, Stoler J, Chen E, Geleske T, Council on Genetics (2025) Genetic evaluation of the child with intellectual disability or global developmental delay: clinical report. Pediatrics. https:\/\/doi.org\/10.1542\/peds.2025-072219","journal-title":"Pediatrics"},{"key":"7519_CR24","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.ymgme.2021.07.012","volume":"134","author":"K Hart","year":"2021","unstructured":"Hart K, Rohrwasser A, Wallis H, Golsan H, Shao J, Anderson T, Wang X, Szabo-Fresnais N, Morrissey M, Kay DM et al (2021) Prospective identification by neonatal screening of patients with guanidinoacetate methyltransferase deficiency. Mol Genet Metab 134:60\u201364. https:\/\/doi.org\/10.1016\/j.ymgme.2021.07.012","journal-title":"Mol Genet Metab"},{"key":"7519_CR25","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2023-062100","author":"MA Ream","year":"2023","unstructured":"Ream MA, Lam WKK, Grosse SD, Ojodu J, Jones E, Prosser LA, Rose AM, Comeau AM, Tanksley S, Powell CM, Kemper AR (2023) Evidence and recommendation for guanidinoacetate methyltransferase deficiency newborn screening. Pediatrics. https:\/\/doi.org\/10.1542\/peds.2023-062100","journal-title":"Pediatrics"},{"key":"7519_CR26","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1212\/01.wnl.0000230152.25203.01","volume":"67","author":"A Schulze","year":"2006","unstructured":"Schulze A, Hoffmann GF, Bachert P, Kirsch S, Salomons GS, Verhoeven NM, Mayatepek E (2006) Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency. Neurology 67:719\u2013721. https:\/\/doi.org\/10.1212\/01.wnl.0000230152.25203.01","journal-title":"Neurology"},{"key":"7519_CR27","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.ejpn.2018.02.007","volume":"22","author":"Y Khaikin","year":"2018","unstructured":"Khaikin Y, Sidky S, Abdenur J, Anastasi A, Ballhausen D, Buoni S, Chan A, Cheillan D, Dorison N, Goldenberg A et al (2018) Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: an international retrospective cohort study. Eur J Paediatr Neurol 22:369\u2013379. https:\/\/doi.org\/10.1016\/j.ejpn.2018.02.007","journal-title":"Eur J Paediatr Neurol"},{"key":"7519_CR28","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1136\/jmedgenet-2013-101658","volume":"50","author":"JM van de Kamp","year":"2013","unstructured":"van de Kamp JM, Betsalel OT, Mercimek-Mahmutoglu S, Abulhoul L, Grunewald S, Anselm I, Azzouz H, Bratkovic D, de Brouwer A, Hamel B et al (2013) Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. J Med Genet 50:463\u2013472. https:\/\/doi.org\/10.1136\/jmedgenet-2013-101658","journal-title":"J Med Genet"},{"key":"7519_CR29","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1002\/humu.22511","volume":"35","author":"S Mercimek-Mahmutoglu","year":"2014","unstructured":"Mercimek-Mahmutoglu S, Ndika J, Kanhai W, de Villemeur TB, Cheillan D, Christensen E, Dorison N, Hannig V, Hendriks Y, Hofstede FC et al (2014) Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene. Hum Mutat 35:462\u2013469. https:\/\/doi.org\/10.1002\/humu.22511","journal-title":"Hum Mutat"},{"key":"7519_CR30","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1111\/j.1399-0004.2010.01460.x","volume":"79","author":"JM van de Kamp","year":"2011","unstructured":"van de Kamp JM, Mancini GM, Pouwels PJ, Betsalel OT, van Dooren SJ, de Koning I, Steenweg ME, Jakobs C, van der Knaap MS, Salomons GS (2011) Clinical features and X-inactivation in females heterozygous for creatine transporter defect. Clin Genet 79:264\u2013272. https:\/\/doi.org\/10.1111\/j.1399-0004.2010.01460.x","journal-title":"Clin Genet"},{"key":"7519_CR31","doi-asserted-by":"publisher","DOI":"10.3390\/genes14010030","author":"I Halfmeyer","year":"2022","unstructured":"Halfmeyer I, Bartolomaeus T, Popp B, Radtke M, Helms T, Hentschel J, Popp D, Jamra RA (2022) Approach to cohort-wide re-analysis of exome data in 1000 individuals with neurodevelopmental disorders. Genes (Basel). https:\/\/doi.org\/10.3390\/genes14010030","journal-title":"Genes (Basel)"},{"key":"7519_CR32","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1086\/320595","volume":"68","author":"GS Salomons","year":"2001","unstructured":"Salomons GS, van Dooren SJ, Verhoeven NM, Cecil KM, Ball WS, Degrauw TJ, Jakobs C (2001) X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. Am J Hum Genet 68:1497\u20131500. https:\/\/doi.org\/10.1086\/320595","journal-title":"Am J Hum Genet"},{"key":"7519_CR33","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1007\/s00439-006-0162-9","volume":"119","author":"AJ Clark","year":"2006","unstructured":"Clark AJ, Rosenberg EH, Almeida LS, Wood TC, Jakobs C, Stevenson RE, Schwartz CE, Salomons GS (2006) X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology. Hum Genet 119:604\u2013610. https:\/\/doi.org\/10.1007\/s00439-006-0162-9","journal-title":"Hum Genet"},{"key":"7519_CR34","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1111\/ncn3.12726","volume":"11","author":"B Turan","year":"2023","unstructured":"Turan B, G\u00f6kta\u015f E, S\u00f6nmez FM, Aydin HI, Aydogdu D, Zamani AG, Yildirim MS (2023) Cerebral creatine deficiency syndrome with a novel missense variant in SLC6A8 gene. Neurol Clin Neurosci 11:286\u2013288. https:\/\/doi.org\/10.1111\/ncn3.12726","journal-title":"Neurol Clin Neurosci"},{"key":"7519_CR35","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1093\/brain\/awab395","volume":"145","author":"S Hiz Kurul","year":"2022","unstructured":"Hiz Kurul S, Oktay Y, Topf A, Szabo NZ, Gungor S, Yaramis A, Sonmezler E, Matalonga L, Yis U, Schon K et al (2022) High diagnostic rate of trio exome sequencing in consanguineous families with neurogenetic diseases. Brain 145:1507\u20131518. https:\/\/doi.org\/10.1093\/brain\/awab395","journal-title":"Brain"},{"key":"7519_CR36","first-page":"914","volume":"58","author":"S Stockler","year":"1996","unstructured":"Stockler S, Isbrandt D, Hanefeld F, Schmidt B, von Figura K (1996) Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. Am J Hum Genet 58:914\u2013922","journal-title":"Am J Hum Genet"},{"key":"7519_CR37","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.medcli.2009.06.065","volume":"133","author":"A Sempere","year":"2009","unstructured":"Sempere A, Fons C, Arias A, Rodriguez-Pombo P, Merinero B, Alcaide P, Capdevila A, Ribes A, Duque R, Eiris J et al (2009) Cerebral creatine deficiency: first Spanish patients harbouring mutations in GAMT gene. Med Clin (Barc) 133:745\u2013749. https:\/\/doi.org\/10.1016\/j.medcli.2009.06.065","journal-title":"Med Clin (Barc)"},{"key":"7519_CR38","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1002\/humu.9238","volume":"23","author":"CB Item","year":"2004","unstructured":"Item CB, Mercimek-Mahmutoglu S, Battini R, Edlinger-Horvat C, Stromberger C, Bodamer O, Muhl A, Vilaseca MA, Korall H, Stockler-Ipsiroglu S (2004) Characterization of seven novel mutations in seven patients with GAMT deficiency. Hum Mutat 23:524. https:\/\/doi.org\/10.1002\/humu.9238","journal-title":"Hum Mutat"},{"key":"7519_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55832-1","volume":"9","author":"HY Liu","year":"2019","unstructured":"Liu HY, Zhou L, Zheng MY, Huang J, Wan S, Zhu A, Zhang M, Dong A, Hou L, Li J et al (2019) Diagnostic and clinical utility of whole genome sequencing in a cohort of undiagnosed Chinese families with rare diseases. Sci Rep 9:19365. https:\/\/doi.org\/10.1038\/s41598-019-55832-1","journal-title":"Sci Rep"},{"key":"7519_CR40","doi-asserted-by":"publisher","unstructured":"Aydin HI, Sonmez FM (2019) A novel mutation in two cousins with guanidinoacetate methyltransferase (GAMT) deficiency presented with autism. Turk J Pediatr 61:92\u201396. https:\/\/doi.org\/10.24953\/turkjped.2019.01.014","DOI":"10.24953\/turkjped.2019.01.014"},{"key":"7519_CR41","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.ymgme.2011.12.022","volume":"105","author":"OT Betsalel","year":"2012","unstructured":"Betsalel OT, Pop A, Rosenberg EH, Fernandez-Ojeda M, Creatine Transporter Research G, Jakobs C, Salomons GS (2012) Detection of variants in SLC6A8 and functional analysis of unclassified missense variants. Mol Genet Metab 105:596\u2013601. https:\/\/doi.org\/10.1016\/j.ymgme.2011.12.022","journal-title":"Mol Genet Metab"},{"key":"7519_CR42","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1093\/clinchem\/48.5.767","volume":"48","author":"CB Item","year":"2002","unstructured":"Item CB, Stromberger C, Muhl A, Edlinger C, Bodamer OA, Schulze A, Surtees R, Leuzzi V, Salomons GS, Jakobs C, Stockler-Ipsiroglu S (2002) Denaturing gradient gel electrophoresis for the molecular characterization of six patients with guanidinoacetate methyltransferase deficiency. Clin Chem 48:767\u2013769","journal-title":"Clin Chem"}],"container-title":["European Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-07519-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00431-026-07519-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-07519-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:39:05Z","timestamp":1792096745000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00431-026-07519-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,11]]}},"alternative-id":["7519"],"URL":"https:\/\/doi.org\/10.1007\/s00431-026-07519-9","relation":{},"ISSN":["1432-1076"],"issn-type":[{"value":"1432-1076","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"19 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Istanbul Medical Faculty (09.04.2026\u20134005180).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent was obtained from the parents or legal guardians of all participants.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"853"}}