A targeted metabolomics approach for clinical diagnosis of inborn errors of metabolism

Jacob, Minnie, Malkawi, Abeer, Albast, Nour, Al Bougha, Salam, Lopata, Andreas, Dasouki, Majed, and Rahman, Anas M. Abdel (2018) A targeted metabolomics approach for clinical diagnosis of inborn errors of metabolism. Analytica Chimica Acta, 1025. pp. 141-153.

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Abstract

Metabolome, the ultimate functional product of the genome, can be studied through identification and quantification of small molecules. The global metabolome influences the individual phenotype through clinical and environmental interventions. Metabolomics has become an integral part of clinical research and allowed for another dimension of better understanding of disease pathophysiology and mechanism. More than 95% of the clinical biochemistry laboratory routine workload is based on small molecular identification, which can potentially be analyzed through metabolomics. However, multiple challenges in clinical metabolomics impact the entire workflow and data quality, thus the biological interpretation needs to be standardized for a reproducible outcome. Herein, we introduce the establishment of a comprehensive targeted metabolomics method for a panel of 220 clinically relevant metabolites using Liquid chromatography-tandem mass spectrometry (LC-MS/MS) standardized for clinical research. The sensitivity, reproducibility and molecular stability of each targeted metabolite (amino acids, organic acids, acylcarnitines, sugars, bile acids, neurotransmitters, polyamines, and hormones) were assessed under multiple experimental conditions. The metabolic tissue distribution was determined in various rat organs. Furthermore, the method was validated in dry blood spot (DBS) samples collected from patients known to have various inborn errors of metabolism (IEMs). Using this approach, our panel appears to be sensitive and robust as it demonstrated differential and unique metabolic profiles in various rat tissues. Also, as a prospective screening method, this panel of diverse metabolites has the ability to identify patients with a wide range of IEMs who otherwise may need multiple, time-consuming and expensive biochemical assays causing a delay in clinical management.

Item ID: 54015
Item Type: Article (Research - C1)
ISSN: 1873-4324
Keywords: dried blood spot, genetic disorder, inborn errors of metabolism, inherited disease, mass spectrometry, metabolomics, targeted metabolomics
Funders: National Health and Medical Research Council (NHMRC), King Faisal Hospital and Research Center (KFSHRC)
Projects and Grants: NHMRC Grant No. 1086656
Date Deposited: 13 Jun 2018 07:35
FoR Codes: 10 TECHNOLOGY > 1004 Medical Biotechnology > 100402 Medical Biotechnology Diagnostics (incl Biosensors) @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 40%
92 HEALTH > 9202 Health and Support Services > 920203 Diagnostic Methods @ 60%
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