{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:58:49Z","timestamp":1761101929492},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,7,2]],"date-time":"2010-07-02T00:00:00Z","timestamp":1278028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>X\u2010linked cerebral creatine deficiency is caused by the deficiency of the creatine transporter encoded by the <jats:italic>SLC6A8<\/jats:italic> gene. Here, we report two half\u2010brothers with this condition and characterize creatine transport in human fibroblasts. The propositus presented at 6 months of age with delays in development and slow progress since then with no regression. Seizures started at 3.5 years of age and responded well to treatment with anticonvulsants. He had failure to thrive with all growth parameters (including head size) at or below the fifth centile. Brain MRI indicated hemispheric white matter abnormalities, while MR spectroscopy indicated markedly reduced creatine peak. Biochemical testing indicated increased urine creatine\/creatinine ratio, with normal plasma creatine and guanidinoacetate. To confirm the diagnosis, we measured <jats:sup>[14]<\/jats:sup>C\u2010creatine transport in fibroblasts. <jats:sup>[14]<\/jats:sup>C\u2010Creatine transport in normal human fibroblasts was linear for up to 2\u2009hr at 37\u00b0C. Kinetic studies indicated the presence of a single saturable creatine transporter with a K<jats:sub>m<\/jats:sub> of 34.7\u2009\u00b1\u20092.5\u2009\u00b5M. Fibroblasts from the propositus lacked creatine transport. DNA testing indicated hemizygosity for a novel deletion producing a frameshift (c.974_975delCA, p.Thr325SerfsX139) in the creatine transporter gene. His 12\u2010year\u2010old half\u2010brother had similar biochemical and clinical abnormalities except for the presence of macrocephaly and the absence of seizures. The mother had history of seizures in childhood, but had normal development. These results show that human fibroblasts have a single major creatine transporter and that measurement of its specific activity can confirm creatine transporter deficiency. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33551","type":"journal-article","created":{"date-parts":[[2010,7,21]],"date-time":"2010-07-21T13:48:03Z","timestamp":1279720083000},"page":"1979-1983","source":"Crossref","is-referenced-by-count":22,"title":["Creatine transporter deficiency in two half\u2010brothers"],"prefix":"10.1002","volume":"152A","author":[{"given":"Orly","family":"Ardon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina Amat di San","family":"Filippo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gajja S.","family":"Salomons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Longo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,7,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309171200"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307911200"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2007.07.010"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-008-0125-5"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.27.061406.093621"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/13554790802060821"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0162-9"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(95)80155-F"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/340092"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000239153.39710.81"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(97)00145-6"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2008.04.003"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004703-200508000-00003"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-008-1063-y"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/422102"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20532"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/320595"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024405821638"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-6486-9_8"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050857"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2005.04.022"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2810021"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1107"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.33551","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33551","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T20:07:17Z","timestamp":1696709237000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,20]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2010,8]]}},"alternative-id":["10.1002\/ajmg.a.33551"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33551","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,7,20]]}}}