PracticeUpdate Conference Series - SSIEM 2018

NMR Analysis Helps Diagnose a Variety of Inborn Errors of Metabolism Nuclear magnetic resonance (NMR) spectroscopy proves effective for fast quantification of a wide range of metabolites. A total of 60 diseases of seven substance classes identifiable by conventional methods have been identified using 1H-NMR spectroscopy, reports a comparative, 3-year metabolic laboratory study. NMR spectroscopy is used to study the structure of molecules, interaction of various molecules, kinetics or dynamics of molecules, and the composition of mixtures of biological or synthetic solutions or composites.

Claire Cannet, of Bruker BioSpin GmbH in Rheinstetten, Germany, and colleagues evaluated quantitative NMR analysis for 250 metabolites in seven disease categories. Over 3 years, 6000 urine samples from a metabolic laboratory in Heidelberg were analyzed in parallel with NMR. In addition, 600 urine samples of healthy children were analyzed to generate reference values for comparison with

NMR nuclear spectroscopy complements other structural and analytical techniques such as X-ray, crystallography, and mass spectrometry. The advantage of NMR is the unique ability of a nuclear spectrometer to allow both nondestructive and quantitative study of molecules in solution and in solid state, as well as to enable the study of biological fluids. Instead of a single biomarker, NMR can employ complex patterns of metabolite concentrations as a spectral fingerprint of different diseases. Manfred Spraul, PhD, also of Bruker BioSpin GmbH, said in Clinicalomics.com, “You will, of course, see large concentrations of any metabolite, but you will also see slight changes of several metabolites at the same time--which is difficult for other analytical methods.” Scientists and clinicians can examine a broad array of health- related factors through the lens of metabolic profiles. These profiles hold the potential to save lives and lower healthcare costs by enabling better healthcare management and earlier treatment. The B.I.QUANT-UR was a 2017 innovation for analysis and quantification of metabolites from urine samples using NMR. The module accompanies the 600-MHz NMR Avance in vitro diagnostics research platform. The automated module provides reproducible quantification of up to 150 different metabolites in urine at a rate of 80–100 samples daily, with specific versions for children/adults and neonates. These age groups account for the substantial differences in the ionic matrix of these samples. The versions allow for both targeted and nontargeted approaches. Dr. Spraul stated in a press release, “Using the AVANCE in vitro diagnostics research platform, we have built an NMR database of over 240 metabolites related to inborn errors of metabolism, which is supplemented by an even larger database of metabolites relevant for general health and phenotype assessment. Being able to identify and quantify 150 metabolites simultaneously in a single run, without chromatography or expensive isotopic standards, offers significant cost and throughput benefits.” Ms. Cannet concluded that in this 3-year assessment, NMR analysis was shown to be an excellent tool for fast quantification of a wide range of metabolites, which until now have required various analytical methods.

Claire Cannet

those obtained from the treated group, Reference value cut-off decisions could be determined for 150 of 250 metabolites. These values provided good congruency with age-matched controls. Targeted analysis provided key metabolites found in 56 diseases. In four lysosomal storage diseases, metabolic profiling provided a preliminary hint for the underlying disease. A total of 60 diseases of seven substance classes identified by multiple conventional methods could also be identified by NMR spectroscopy. " Being able to identify and quantify 150 metabolites simultaneously in a single run, without chromatography or expensive isotopic standards, offers significant cost and throughput benefits. " Ms. Cannet explained that NMR analysis in urine is a new approach for quantitative measurement of a high number of analytes of various substance classes. Urine metabolite concentrations can vary substantially both between individuals and within the same individual at different time points. Diet, disease, exercise, and environmental conditions can all affect excreted metabolites in urine. Though these variables can render urine metabolic analysis a complex process, they also allow for an information-rich resource with a large number of applications.

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PRACTICEUPDATE CONFERENCE SERIES • SSIEM 2018 18