In:
Clinical Chemistry, Oxford University Press (OUP), Vol. 48, No. 10 ( 2002-10-01), p. 1772-1778
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 μmol/L [mean (SD) for neurologically normal controls was 1.16 (0.59) μmol/L], Cr+Crn was 15–29 μmol/L [reference limit in our laboratory, 79 (38) μmol/L] . Urinary GAA was 2.4–5.8 μmol/L [reference, 311 (191) μmol/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 μmol/L, respectively), and Cr+Crn was decreased in plasma (10.7 μmol/L) and urine (2.1 mmol/L). GAA was increased in the parents’ plasmas and in the mother’s urine. Conclusion: The assessment of GAA is a new tool for the detection of both GAMT and AGAT deficiencies.
Type of Medium:
Online Resource
ISSN:
0009-9147
,
1530-8561
DOI:
10.1093/clinchem/48.10.1772
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2002
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