Engelke Udo F H, Tassini Maria, Hayek Joseph, de Vries Maaike, Bilos Appie, Vivi Antonio, Valensin Gianni, Buoni Sabrina, Zannolli Raffaella, Brussel Wim, Kremer Berry, Salomons Gajja S, Veendrick-Meekes Monique J B M, Kluijtmans Leo A J, Morava Eva, Wevers Ron A
Laboratory of Pediatrics and Neurology, Nijmegen Medical Center, Radboud University, Nijmegen, The Netherlands.
NMR Biomed. 2009 Jun;22(5):538-44. doi: 10.1002/nbm.1367.
In patients with guanidinoacetate methyltransferase (GAMT) deficiency several parameters may point towards the diagnosis of GAMT deficiency. These include the low levels of creatine and creatinine in urine, the high concentration of guanidinoacetic acid (GAA) in urine and the low levels of creatine and creatinine in the cerebrospinal fluid (CSF). In this study, body fluids from 10 GAMT deficient patients were analysed using (1)H NMR spectroscopy. The urine 1D (1)H NMR spectra of all the patients showed a doublet resonance at 3.98 ppm (pH 2.50) derived from GAA present in high concentration. For this compound, a good recovery and good correlation was found between an LC-MS/MS method and (1)H NMR spectroscopy. In CSF NMR spectra of these patients, the singlet resonances of creatine and creatinine (3.05 and 3.13 ppm, respectively) were absent (normally always present in (1)H NMR spectra of CSF). Due to overlap by other resonances, the doublet of GAA could not be observed. Our data demonstrate that (1)H NMR spectroscopy of urine and CSF can be used to diagnose patients with GAMT deficiency.
在患有胍基乙酸甲基转移酶（GAMT）缺乏症的患者中，有几个参数可能指向GAMT缺乏症的诊断。这些参数包括尿液中肌酸和肌酐水平较低、尿液中胍基乙酸（GAA）浓度较高以及脑脊液（CSF）中肌酸和肌酐水平较低。在本研究中，使用核磁共振氢谱（¹H NMR）对10例GAMT缺乏症患者的体液进行了分析。所有患者的尿液一维¹H NMR谱在3.98 ppm（pH 2.50）处显示出一个双峰共振，这是由高浓度的GAA产生的。对于该化合物，在液相色谱-串联质谱（LC-MS/MS）方法和¹H NMR光谱之间发现了良好的回收率和良好的相关性。在这些患者的脑脊液NMR谱中，肌酸和肌酐的单峰共振（分别为3.05和3.13 ppm）不存在（正常情况下，脑脊液的¹H NMR谱中总是存在）。由于被其他共振峰重叠，无法观察到GAA的双峰。我们的数据表明，尿液和脑脊液的¹H NMR光谱可用于诊断GAMT缺乏症患者。
