Guanidinoacetic acid (GAA) is an important metabolite formed from glycine and arginine in the first step of the creatine synthesis pathway. Creatine (Cr) and phosphocreatine play an important role in the storage and transmission of energy in various tissues. Two enzymes are involved in Cr biosynthesis: arginine glycine amidinotransferase (AGAT, EC 2.1.4.1), which converts arginine and glycine to ornithine and guanidinoacetate (GAA), and S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase (GAMT, EC 2.1.1.2) and converts GAA to Cr. Cr is then transported to tissues via creatine transporters (SLC6A8), where it is converted non-enzymatically to creatinine. Creatine deficiency syndrome (CDS) consists of three inborn errors of metabolism: AGAT deficiency (OMIM 602360), GAMT deficiency (OMIM 601240) and SLC6A8 deficiency (OMIM 3000036).

Diagnosis is possible by measuring guanidinoacetate, creatine in plasma and urine. Patients with GAMT deficiency typically exhibit normal to low creatinine, very elevated GAA, and low Cr. Patients with AGAT deficiency typically exhibit normal to low creatinine, low GAA, and normal to low Cr. In comparison, elevated creatinine, normal GAA, normal to low Cr, and an elevated creatinine: creatine ratio characterizes patients with creatine transporter defect.