Engelke Udo F H, Liebrand-van Sambeek Maria L F, de Jong Jan G N, Leroy Jules G, Morava Eva, Smeitink Jan A M, Wevers Ron A
University Medical Center Nijmegen, Laboratory of Pediatrics and Neurology, NL-6500 HB Nijmegen, The Netherlands.
Clin Chem. 2004 Jan;50(1):58-66. doi: 10.1373/clinchem.2003.020214. Epub 2003 Nov 18.
There is no comprehensive analytical technique to analyze N-acetylated metabolites in urine. Many of these compounds are involved in inborn errors of metabolism. In the present study, we examined the potential of proton nuclear magnetic resonance ((1)H-NMR) spectroscopy as a tool to identify and quantify N-acetylated metabolites in urine of patients with various inborn errors of metabolism.
We performed (1)H-NMR spectroscopy on a 500 MHz spectrometer. Using a combination of one- and two-dimensional correlation spectroscopy (COSY) (1)H-NMR spectra, we were able to assign and quantify resonances of characteristic N-acetylated compounds products in urine of patients with 13 inborn errors of metabolism.
The disease-specific N-acetylated metabolites were excreted at concentrations >100 micromol/mmol of creatinine in the patients' urine. In control urine samples, the concentration of individual N-acetyl-containing compounds was <40 micromol/mmol of creatinine. The combination of one- and two-dimensional COSY NMR spectroscopy led to the correct diagnosis of nine different inborn errors of metabolism. No abnormalities were observed in the spectra of urine from patients with G(M1)- or G(M2)-gangliosidosis. We also determined the (1)H-NMR characteristics of N-acetylated metabolites that may be relevant to human metabolism.
(1)H-NMR spectroscopy may be used to identify and quantify N-acetylated metabolites of diagnostic importance for the field of inborn errors of metabolism.
目前尚无用于分析尿液中N - 乙酰化代谢物的综合分析技术。这些化合物中的许多都与先天性代谢缺陷有关。在本研究中，我们研究了质子核磁共振（(1)H - NMR）光谱作为一种工具来鉴定和定量患有各种先天性代谢缺陷患者尿液中N - 乙酰化代谢物的潜力。
我们在500 MHz光谱仪上进行(1)H - NMR光谱分析。通过结合一维和二维相关光谱（COSY）(1)H - NMR光谱，我们能够对13种先天性代谢缺陷患者尿液中特征性N - 乙酰化化合物产物的共振峰进行归属和定量。
疾病特异性的N - 乙酰化代谢物在患者尿液中的排泄浓度>100微摩尔/毫摩尔肌酐。在对照尿液样本中，单个含N - 乙酰基化合物的浓度<40微摩尔/毫摩尔肌酐。一维和二维COSY NMR光谱的结合使得能够正确诊断出9种不同的先天性代谢缺陷。在患有G(M1) - 或G(M2) - 神经节苷脂沉积症患者的尿液光谱中未观察到异常。我们还确定了可能与人类代谢相关的N - 乙酰化代谢物的(1)H - NMR特征。
(1)H - NMR光谱可用于鉴定和定量对先天性代谢缺陷领域具有诊断重要性的N - 乙酰化代谢物。
