title: 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.
abstract: BACKGROUND
  Disorders of creatine metabolism arise from genetic alterations of arginine:glycine amidinotransferase (AGAT), guanidinoacetate methyltransferase (GAMT), and the creatine transporter. We developed a strategy for the detection of AGAT and GAMT defects by measurement of guanidinoacetate (GAA) and creatine plus creatinine (Cr+Crn) in biological fluids.
  
  
  METHODS
  Three patients with AGAT deficiency from the same pedigree and their eight relatives, as well as a patient affected by a GAMT defect and his parents were analyzed by a new HPLC procedure in comparison with 90 controls. The method, which uses precolumn derivatization with benzoin, separation with a reversed-phase column, and fluorescence detection, has shown good precision and sensitivity and requires minimal sample handling.
  
  
  RESULTS
  In the three AGAT patients, plasma GAA was 0.01-0.04 micro mol/L [mean (SD) for neurologically normal controls was 1.16 (0.59) micromol/L], Cr+Crn was 15-29 micro mol/L [reference limit in our laboratory, 79 (38) micromol/L]. Urinary GAA was 2.4-5.8 micro mol/L [reference, 311 (191) micromol/L], and Cr+Crn was 2.1-3.3 mmol/L [reference, 9.9 (4.1) mmol/L]. We found a smaller decrease in GAA and Cr+Crn in some carriers of an AGAT defect. In the patient with GAMT deficiency, plasma and urine GAA was increased (18.6 and 1783 micromol/L, respectively), and Cr+Crn was decreased in plasma (10.7 micromol/L) and urine (2.1 mmol/L). GAA was increased in the parents' plasmas and in the mother's urine.
  
  
  CONCLUSIONS
  The assessment of GAA is a new tool for the detection of both GAMT and AGAT deficiencies.
mesh_terms: D000579:Amidinotransferases / Q000172:deficiency* / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D001826:Body Fluids / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003401:Creatine / Q000032:analysis* / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000032:analysis* / Q000097:blood / Q000652:urine; D005998:Glycine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000652:urine; D050937:Guanidinoacetate N-Methyltransferase; D006579:Heterozygote; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000172:deficiency* / Q000235:genetics; D010375:Pedigree
chemical_list: D015415:Biomarkers; D003404:Creatinine; D008780:Methyltransferases; C494506:GAMT protein, human; D050937:Guanidinoacetate N-Methyltransferase; D000579:Amidinotransferases; C020681:glycine amidinotransferase; C004946:glycocyamine; D003401:Creatine; D005998:Glycine