Pulido Ninna, Guevara-Morales Johana M, Rodriguez-López Alexander, Pulido Álvaro, Díaz Jhon, Edrada-Ebel Ru Angelie, Echeverri-Peña Olga Y
San Ignacio University Hospital, Bogota 4665684, Colombia.
Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Cra 7 # 43-82, Edificio 54 Lab 303A, Bogota 4665684, Colombia.
Metabolites. 2021 Dec 20;11(12):891. doi: 10.3390/metabo11120891.
The utility of low-resolution H-NMR analysis for the identification of biomarkers provided evidence for rapid biochemical diagnoses of organic acidemia and aminoacidopathy. H-NMR, with a sensitivity expected for a field strength of 400 MHz at 64 scans was used to establish the metabolomic urine sample profiles of an infant population diagnosed with small molecule Inborn Errors of Metabolism (smIEM) compared to unaffected individuals. A qualitative differentiation of the H-NMR spectral profiles of urine samples obtained from individuals affected by different organic acidemias and aminoacidopathies was achieved in combination with GC-MS. The smIEM disorders investigated in this study included phenylalanine metabolism; isovaleric, propionic, 3-methylglutaconicm and glutaric type I acidemia; and deficiencies in medium chain acyl-coenzyme and holocarboxylase synthase. The observed metabolites were comparable and similar to those reported in the literature, as well as to those detected with higher-resolution NMR. In this study, diagnostic marker metabolites were identified for the smIEM disorders. In some cases, changes in metabolite profiles differentiated post-treatments and follow-ups while allowing for the establishment of different clinical states of a biochemical disorder. In addition, for the first time, a H-NMR-based biomarker profile was established for holocarboxylase synthase deficiency spectrum.
低分辨率氢核磁共振（H-NMR）分析在生物标志物识别方面的实用性为有机酸血症和氨基酸病的快速生化诊断提供了证据。使用在64次扫描下预期场强为400 MHz灵敏度的H-NMR，来建立与未受影响个体相比，被诊断患有小分子先天性代谢缺陷（smIEM）的婴儿群体的代谢组学尿液样本图谱。结合气相色谱-质谱联用（GC-MS）实现了对来自不同有机酸血症和氨基酸病患者尿液样本的H-NMR光谱图谱的定性区分。本研究中调查的smIEM疾病包括苯丙氨酸代谢；异戊酸、丙酸、3-甲基戊二酸和I型戊二酸血症；以及中链酰基辅酶和全羧化酶合成酶缺乏症。观察到的代谢物与文献报道的以及用高分辨率核磁共振检测到的代谢物具有可比性和相似性。在本研究中，确定了smIEM疾病的诊断标志物代谢物。在某些情况下，代谢物谱的变化区分了治疗后和随访情况，同时能够确定生化疾病的不同临床状态。此外，首次建立了基于H-NMR的全羧化酶合成酶缺乏谱生物标志物图谱。
