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1 Dipartimento di Medicina Sperimentale e Patologia, Università degli Studi di Roma "La Sapienza", Viale del Policlinico 155, 00161 Rome, Italy.
2 Dipartimento di Scienze Neurologiche e Psichiatriche dell’ Età Evolutiva, Università degli Studi di Roma "La Sapienza", Via dei Sabelli 108, 00185 Rome, Italy.
3 Divisione di Neuropsichiatria Infantile, Istituto Scientifico Stella Maris, Università di Pisa, Viale del Tirreno 331, 56021 Calabrone (Pisa), Italy.
aAuthor for correspondence. Fax 39-06-49918278; e-mail cardu_cla{at}yahoo.com.
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.
The following articles in journals at HighWire Press have cited this article:
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  D. Cheillan, G. S. Salomons, C. Acquaviva, C. Boisson, P. Roth, M.-P. Cordier, L. Francois, C. Jakobs, and C. Vianey-Saban Prenatal diagnosis of guanidinoacetate methyltransferase deficiency: increased guanidinoacetate concentrations in amniotic fluid. Clin. Chem., April 1, 2006; 52(4): 775 - 777. [Full Text] [PDF]
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 F L Raymond X linked mental retardation: a clinical guide J. Med. Genet., March 1, 2006; 43(3): 193 - 200. [Abstract] [Full Text] [PDF]
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S. Cognat, D. Cheillan, M. Piraud, B. Roos, C. Jakobs, and C. Vianey-Saban Determination of Guanidinoacetate and Creatine in Urine and Plasma by Liquid Chromatography-Tandem Mass Spectrometry Clin. Chem., August 1, 2004; 50(8): 1459 - 1461. [Full Text] [PDF]
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 A. Schmidt, B. Marescau, E. A. Boehm, W. K. J. Renema, R. Peco, A. Das, R. Steinfeld, S. Chan, J. Wallis, M. Davidoff, et al. Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency Hum. Mol. Genet., May 1, 2004; 13(9): 905 - 921. [Abstract] [Full Text] [PDF]
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