Abstract
Guanidinoacetate (GA), Creatine (Cr), and creatinine are small polar molecules. It is well recognized that Cr plays an important role in energy transmission and storage in cells and tissues with high energy demand. Recent developments have revealed alteration in the levels of the above-mentioned metabolites in different disease states, i.e. guanidinoacetate methyltransferase (GAMT) deficiency, L-arginine:glycine amidino transferase (AGAT) deficiency and Cr transporter (SLC6A8) deficiency. This group of diseases is referred to as creatine deficiency syndromes (CDS) and can be detected in vivo by 1H magnetic resonance spectroscopy (MRS) of the brain. Quantification of GA and Cr in body fluids forms the biochemical basis for the (differential) diagnosis of the CDS. This current chapter describes a detailed procedure for the simultaneous measurement of GA and Cr in urine, plasma, and cerebrospinal fluid employing Stable-Isotope Dilution Gas Chromatography-Mass Spectrometry. In addition, recent analytical developments using tandem mass spectrometry for the measurement of GA and Cr are briefly discussed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Salomons GS, Wyss M, Jakobs C (2005) Creatine. In: Coates P, Blackman MR, Cragg G, Levine M, Moss J, White J (eds) Encyclopedia of Dietary Supplements. Marcel Dekker, pp 151–158
Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Phys Rev 80:1107–1213
Item CB, Stöckler-Ipsiroglu S, Stromberger C, Mühl A, Alessandrì MG, Bianchi MC, Tosetti M, Fornai F, Cioni G (2001) Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet 69:1127–1133
Battini R, Leuzzi V, Carducci C, Tosetti M, Bianchi MC, Item CB, Stöckler-Ipsiroglu S, Cioni G (2002) Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree. Mol Genet Metab 77:326–331
Salomons GS, Johnston K, Plawner L, Cooper L, Barkovich J, Verhoeven NM, Jakobs C (2005) The second family with AGAT deficiency (creatine biosynthesis defect); diagnosis, treatment and the first prenatal diagnosis. J Inherit Metab Dis 28:224
Stromberger C, Bodamer OA, Stöckler-Ipsiroglu S (2003) Clinical characteristics and diagnostic clues in inborn errors of creatine metabolism. J Inherit Metab Dis 26:299–308
Salomons GS, van Dooren SJ, Verhoeven NM, Marsden D, Schwartz C, Cecil KM, DeGrauw TJ, Jakobs C (2003) X-linked creatine transporter defect: an overview. J Inherit Metab Dis 26:309–318
Rosenberg EH, Almeida LS, Kleefstra T, deGrauw RS, Yntema HG, Bahi N, Moraine C, Ropers HH, Fryns JP, deGrauw TJ, Jakobs C, Salomons GS (2004) High prevalence of SLC6A8 deficiency in X-linked mental retardation. Am J Hum Genet 75:97–105
Mancini GM, Catsman-Berrevoets CE, de Coo IF, Aarsen FK, Kamphoven JH, Huijmans JG, Duran M, van der Knaap MS, Jakobs C, Salomons GS (2004) Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X-linked mental retardation in two unrelated Dutch families. Am J Med Genet A 132:288–295
Verhoeven NM, Salomons GS, Jakobs C (2005) Laboratory diagnosis of defects of creatine biosynthesis and transport. Clin Chim Acta 361:1–9
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 23:835–840
Stöckler S, Marescau B, De Deyn PP, Trijbels JM, Hanefeld F (1997) Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism 46:1189–11939
Struys EA, Jansen EE, ten Brink HJ, Verhoeven NM, van der Knaap MS, Jakobs C (1998) An accurate stable isotope dilution gas chromatographic-mass spectrometric approach to the diagnosis of guanidinoacetate methyltransferase deficiency. J Pharm Biomed Anal 18:659–665
Almeida LS, Verhoeven NM, Roos B, Valongo C, Cardoso ML, Vilarinho L, Salomons GS, Jakobs C (2004) Creatine and guanidinoacetate: diagnostic markers for inborn errors in creatine biosynthesis and transport. Mol Genet Metab 82:214–219
Carducci C, Birarelli M, Leuzzi V, Carducci C, Battini R, Cioni G, Antonozzi I (2002) Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies. Clin Chem 48:1772–1778
Verhoeven NM, Roos B, Struys EA, Salomons GS, van der Knaap MS, Jakobs C (2004) Enzyme assay for diagnosis of guanidinoacetate methyltransferase deficiency. Clin Chem 50:441–443
Verhoeven NM, Schor DS, Roos B, Battini R, Stöckler-Ipsiroglu S, Salomons GS, Jakobs C (2003) Diagnostic enzyme assay that uses stable-isotope-labeled substrates to detect l-arginine:glycine amidinotransferase deficiency. Clin Chem 49:803–805
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 68:1497–1500
Carducci C, Birarelli M, Santagata P, Leuzzi V, Carducci C, Antonozzi I (2001) Automated high-performance liquid chromatographic method for the determination of guanidinoacetic acid in dried blood spots: a tool for early diagnosis of guanidinoacetate methyltransferase deficiency. J Chromatogr B Biomed Sci Appl 755:343–348
Bodamer OA, Bloesch SM, Gregg AR, Stockler-Ipsiroglu S, O’Brien WE (2001) Analysis of guanidinoacetate and creatine by isotope dilution electrospray tandem mass spectrometry. Clin Chim Acta 308:173–178
Cognat S, Cheillan D, Piraud M, Roos B, Jakobs C, Vianey-Saban C (2004) Determination of guanidinoacetate and creatine in urine and plasma by liquid chromatography-tandem mass spectrometry. Clin Chem 50:1459–1461
Carducci C, Santagata S, Leuzzi V, Carducci C, Artiola C, Giovanniello T, Battini R, Antonozzi I (2006) Quantitative determination of guanidinoacetate and creatine in dried blood spot by flow injection analysis-electrospray tandem mass spectrometry. Clin Chim Acta 364:180–187
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Struys, E., Verhoeven-Duif, N., Jakobs, C. (2008). Creatine and its Metabolites. In: Blau, N., Duran, M., Gibson, K. (eds) Laboratory Guide to the Methods in Biochemical Genetics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-76698-8_32
Download citation
DOI: https://doi.org/10.1007/978-3-540-76698-8_32
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-76697-1
Online ISBN: 978-3-540-76698-8
eBook Packages: MedicineMedicine (R0)