H-Nuclear Magnetic Resonance Analysis of Urine As Diagnostic Tool for Organic Acidemias and Aminoacidopathies

Overview

Journal Metabolites

Publisher MDPI

Date 2021 Dec 23

PMID 34940649

Citations 5

Authors

Ninna Pulido

Johana M Guevara-Morales

Alexander Rodriguez-Lopez

Alvaro Pulido

Jhon Diaz

Ru Angelie Edrada-Ebel

Olga Y Echeverri-Pena

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

NMR Spectroscopy in Diagnosis and Monitoring of Methylmalonic and Propionic Acidemias.

Deleanu C, Nicolescu A Biomolecules. 2024; 14(5).

PMID: 38785935 PMC: 11117674. DOI: 10.3390/biom14050528.

Phenylketonuria (PKU) Urinary Metabolomic Phenotype Is Defined by Genotype and Metabolite Imbalance: Results in 51 Early Treated Patients Using Ex Vivo H-NMR Analysis.

Cannet C, Bayat A, Frauendienst-Egger G, Freisinger P, Spraul M, Himmelreich N Molecules. 2023; 28(13).

PMID: 37446577 PMC: 10343293. DOI: 10.3390/molecules28134916.

Metabolomic Studies in Inborn Errors of Metabolism: Last Years and Future Perspectives.

Cossu M, Pintus R, Zaffanello M, Mussap M, Serra F, Marcialis M Metabolites. 2023; 13(3).

PMID: 36984887 PMC: 10058105. DOI: 10.3390/metabo13030447.

Changes in the Urine Metabolomic Profile in Patients Recovering from Severe COVID-19.

Rosolanka R, Liptak P, Baranovicova E, Bobcakova A, Vysehradsky R, duricek M Metabolites. 2023; 13(3).

PMID: 36984804 PMC: 10058594. DOI: 10.3390/metabo13030364.

A narrative review of metabolomics in the era of "-omics": integration into clinical practice for inborn errors of metabolism.

Hertzog A, Selvanathan A, Devanapalli B, Ho G, Bhattacharya K, Tolun A Transl Pediatr. 2022; 11(10):1704-1716.

PMID: 36345452 PMC: 9636448. DOI: 10.21037/tp-22-105.

References

Schmidt-Sommerfeld E, Penn D, Rinaldo P, Kossak D, Li B, Huang Z . Urinary medium-chain acylcarnitines in medium-chain acyl-CoA dehydrogenase deficiency, medium-chain triglyceride feeding and valproic acid therapy: sensitivity and specificity of the radioisotopic exchange/high performance liquid chromatography.... Pediatr Res. 1992; 31(6):545-51. DOI: 10.1203/00006450-199206000-00002. View

Ulrich E, Akutsu H, Doreleijers J, Harano Y, Ioannidis Y, Lin J . BioMagResBank. Nucleic Acids Res. 2007; 36(Database issue):D402-8. PMC: 2238925. DOI: 10.1093/nar/gkm957. View

Van Hove J, Zhang W, Kahler S, Roe C, Chen Y, Terada N . Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood. Am J Hum Genet. 1993; 52(5):958-66. PMC: 1682046. View

Miller M, Kennedy A, Eckhart A, Burrage L, Wulff J, Miller L . Untargeted metabolomic analysis for the clinical screening of inborn errors of metabolism. J Inherit Metab Dis. 2015; 38(6):1029-39. PMC: 4626538. DOI: 10.1007/s10545-015-9843-7. View

Vernon H . Inborn Errors of Metabolism: Advances in Diagnosis and Therapy. JAMA Pediatr. 2015; 169(8):778-82. DOI: 10.1001/jamapediatrics.2015.0754. View

Kobayashi H, Hasegawa Y, Endo M, Purevsuren J, Yamaguchi S . ESI-MS/MS study of acylcarnitine profiles in urine from patients with organic acidemias and fatty acid oxidation disorders. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 855(1):80-7. DOI: 10.1016/j.jchromb.2006.12.010. View

Eriksson L, Johansson E, Lindgren F, Sjostrom M, Wold S . Megavariate analysis of hierarchical QSAR data. J Comput Aided Mol Des. 2003; 16(10):711-26. DOI: 10.1023/a:1022450725545. View

Bouatra S, Aziat F, Mandal R, Guo A, Wilson M, Knox C . The human urine metabolome. PLoS One. 2013; 8(9):e73076. PMC: 3762851. DOI: 10.1371/journal.pone.0073076. View

Engelke U, Liebrand-van Sambeek M, de Jong J, Leroy J, Morava E, Smeitink J . N-acetylated metabolites in urine: proton nuclear magnetic resonance spectroscopic study on patients with inborn errors of metabolism. Clin Chem. 2003; 50(1):58-66. DOI: 10.1373/clinchem.2003.020214. View

10.

Bales J, Higham D, Howe I, Nicholson J, Sadler P . Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem. 1984; 30(3):426-32. View

11.

Rinaldo P, Cowan T, Matern D . Acylcarnitine profile analysis. Genet Med. 2008; 10(2):151-6. DOI: 10.1097/GIM.0b013e3181614289. View

12.

Villani G, Gallo G, Scolamiero E, Salvatore F, Ruoppolo M . "Classical organic acidurias": diagnosis and pathogenesis. Clin Exp Med. 2016; 17(3):305-323. DOI: 10.1007/s10238-016-0435-0. View

13.

Kind T, Wohlgemuth G, Lee D, Lu Y, Palazoglu M, Shahbaz S . FiehnLib: mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography/mass spectrometry. Anal Chem. 2009; 81(24):10038-48. PMC: 2805091. DOI: 10.1021/ac9019522. View

14.

Miller M, Cusmano-Ozog K, Oglesbee D, Young S . Laboratory analysis of acylcarnitines, 2020 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020; 23(2):249-258. DOI: 10.1038/s41436-020-00990-1. View

15.

Ismail I, Showalter M, Fiehn O . Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics. Metabolites. 2019; 9(10). PMC: 6835511. DOI: 10.3390/metabo9100242. View

16.

Engelke U, Kremer B, Kluijtmans L, van der Graaf M, Morava E, Loupatty F . NMR spectroscopic studies on the late onset form of 3-methylglutaconic aciduria type I and other defects in leucine metabolism. NMR Biomed. 2006; 19(2):271-8. DOI: 10.1002/nbm.1018. View

17.

Mardhiah M, Azize N, Yakob Y, Affandi O, Hock N, Rowani M . Clinical, biochemical and mutational findings in biotinidase deficiency among Malaysian population. Mol Genet Metab Rep. 2020; 22:100548. PMC: 7144277. DOI: 10.1016/j.ymgmr.2019.100548. View

18.

Triba M, Le Moyec L, Amathieu R, Goossens C, Bouchemal N, Nahon P . PLS/OPLS models in metabolomics: the impact of permutation of dataset rows on the K-fold cross-validation quality parameters. Mol Biosyst. 2014; 11(1):13-9. DOI: 10.1039/c4mb00414k. View

19.

Kang S, Park J, Shin M, Lee H, Oh J, Ryu D . ¹H nuclear magnetic resonance based metabolic urinary profiling of patients with ischemic heart failure. Clin Biochem. 2010; 44(4):293-9. DOI: 10.1016/j.clinbiochem.2010.11.010. View

20.

Xiao C, Hao F, Qin X, Wang Y, Tang H . An optimized buffer system for NMR-based urinary metabonomics with effective pH control, chemical shift consistency and dilution minimization. Analyst. 2009; 134(5):916-25. DOI: 10.1039/b818802e. View