Creatine and guanidinoacetate: diagnostic markers for inborn errors in creatine biosynthesis and transport.

In this study, measurements of guanidinoacetate (GAA) and creatine (Cr) in urine, plasma, and cerebrospinal fluid (CSF) were performed using stable isotope dilution gas chromatography-mass spectrometry. Both compounds were analyzed in a single analysis. Reference values were established for GAA and Cr. These values were age dependent. No differences with gender were observed. Eight guanidinoacetate methyltransferase (GAMT) deficient patients and eight creatine transporter SLC6A8 deficient patients were investigated. In urine, plasma, and CSF of GAMT deficient patients increased levels of GAA are present. The SLC6A8 deficient patients all show increased creatine/creatinine (Cr/Crn) ratio in urine demonstrating the importance of the Cr/Crn ratio as a pathognomonic marker of the SLC6A8 deficiency.