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Three primary Cr deficiencies exists: arginine:glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency and the defect of Cr transporter SLC6A8. Secondary Cr deficiency is characteristic of ornithine\u2010aminotransferase deficiency, whereas non\u2010uniform Cr abnormalities have anecdotally been reported in patients with urea cycle defects (UCDs), a disease category related to arginine metabolism in which Cr must be acquired by <jats:italic>de novo<\/jats:italic> synthesis because of low dietary intake. To evaluate the relationships between ureagenesis and Cr synthesis, we systematically measured plasma Cr in a large series of UCD patients (i.e., OTC, ASS, ASL deficiencies, HHH syndrome and lysinuric protein intolerance). Plasma Cr concentrations in UCDs followed two different trends: patients with OTC and ASS deficiencies and HHH syndrome presented a significant Cr decrease, whereas in ASL deficiency and lysinuric protein intolerance Cr levels were significantly increased (23.5 vs. 82.6 \u03bcmol\/L; p\u2009&lt;\u20090.0001). This trend distribution appears to be regulated upon cellular arginine availability, highlighting its crucial role for both ureagenesis and Cr synthesis. Although decreased Cr contributes to the neurological symptoms in primary Cr deficiencies, still remains to be explored if an altered Cr metabolism may participate to CNS dysfunction also in patients with UCDs. Since arginine in most UCDs becomes a semi\u2010essential aminoacid, measuring plasma Cr concentrations might be of help to optimize the dose of arginine substitution.<\/jats:p>","DOI":"10.1007\/s10545-012-9494-x","type":"journal-article","created":{"date-parts":[[2012,5,29]],"date-time":"2012-05-29T07:06:48Z","timestamp":1338275208000},"page":"647-653","source":"Crossref","is-referenced-by-count":24,"title":["Creatine metabolism in urea cycle defects"],"prefix":"10.1002","volume":"35","author":[{"given":"Sara","family":"Boenzi","sequence":"first","affiliation":[{"name":"Division of Metabolism and Research Unit of Metabolic Biochemistry Bambino Ges\u00f9 Children's Hospital, IRCCS Piazza S. Onofrio 4 Rome 00165 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pastore","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Research Unit of Metabolic Biochemistry Bambino Ges\u00f9 Children's Hospital, IRCCS Piazza S. 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