Comprehensive metabolomics analysis reveals novel biomarkers and pathways in falsely suspected glutaric aciduria Type-1 newborns.

Autor: Sabi EM; Clinical Biochemistry Unit, Pathology Department, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia., AlMogren M; Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, KSA, Saudi Arabia., Sebaa R; Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia., Sumaily KM; Clinical Biochemistry Unit, Pathology Department, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia., AlMalki R; Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, KSA, Saudi Arabia., Mujamammi AH; Clinical Biochemistry Unit, Pathology Department, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia., Abdel Rahman AM; Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, KSA, Saudi Arabia; The Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. Electronic address: aabdelraman46@kfshrc.edu.sa.
Jazyk: angličtina
Zdroj: Clinica chimica acta; international journal of clinical chemistry [Clin Chim Acta] 2024 Apr 15; Vol. 557, pp. 117861. Date of Electronic Publication: 2024 Mar 13.
DOI: 10.1016/j.cca.2024.117861
Abstrakt: Background: Glutaric aciduria type-1 (GA-1) is a rare metabolic disorder due to glutaryl coenzyme A dehydrogenase deficiency, causing elevated levels of glutaryl-CoA and its derivatives. GA-1 exhibits symptoms like macrocephaly, developmental delays, and movement disorders. Timely diagnosis through genetic testing and newborn screening is crucial. However, in some cases, transiently elevated level of glutarylcarnitine (C5DC) challenges accurate diagnosis, highlighting the need for alternative diagnostic methods, like mass spectrometry-based untargeted metabolomics, to identify additional biomarkers for distinguishing falsely suspected GA-1 from healthy newborns.
Methodology: DBS samples from falsely suspected GA-1 newborns (n = 47) and matched control were collected through the NBS program. Untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) was performed to enable biomarker and pathway investigations for significantly altered metabolites.
Results: 582 and 546 were up- and down-regulated metabolites in transient GA-1. 155 endogenous metabolites displayed significant variations compared to the control group. Furthermore, our data identified novel altered metabolic biomarkers, such as N-palmitoylcysteine, heptacarboxyporphyrin, 3-hydroxylinoleoylcarnitine, and monoacylglyceride (MG) (0:0/20:1/0:0), along with perturbed metabolic pathways like sphingolipid and thiamine metabolism associated with the transient elevated C5DC levels in DBS samples.
Conclusions: A distinct metabolic pattern linked to the transient C5DC elevation in newborns was reported to enhance the prediction of the falsely positive cases, which could help avoiding unnecessary medical treatments and minimizing the financial burdens in the health sector.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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