Summary of Study ST002934
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001825. The data can be accessed directly via it's Project DOI: 10.21228/M8T714 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002934 |
| Study Title | Metabolic profiling of newborn DBS samples associated with transit and false elevation of glutarylcarnitine (C5DC) |
| Study Summary | Background: Glutaric aciduria type-1 (GA-1) is a rare autosomal recessive metabolic disorder caused by a glutaryl coenzyme A dehydrogenase (GCDH) deficiency, affecting approximately 1 in 110,000 individuals globally. This enzymatic deficiency leads to abnormal elevations of glutaryl-CoA and its derivatives, specifically glutaric acid (GA), 3-hydroxyglutaric acid (3OHGA), and glutarylcarnitine (C5DC). Clinical manifestations encompass macrocephaly, developmental delays, and movement disorders. Early detection via genetic testing and newborn screening (NBS), utilizing GA-1 biomarkers in dried blood spot (DBS) samples, is vital for prompt intervention. Despite the NBS system, transit-elevated C5DC-containing DBS samples from falsely suspected GA-1 newborns sometimes yield normal results, posing diagnostic sensitivity and specificity challenges. Consequently, there is a growing need for alternative diagnostic tools. Comprehensive mass spectrometry-based untargeted metabolomics offers promise in identifying additional informative biomarkers for distinguishing falsely suspected GA-1 newborns from healthy counterparts. Methodology: In this prospective study, we obtained DBS samples with transit-elevated C5DC levels from falsely suspected GA-1 newborns (n=47) and matched control DBS samples from healthy newborns (n=47) through the NBS program. Metabolites were extracted and analyzed via liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Subsequent multivariate and univariate statistical analyses and feature annotation enabled biomarker and pathway investigations for significantly altered metabolites. Results: Untargeted metabolomics analysis revealed alterations in 582 upregulated and 546 downregulated metabolites. The commonly used GA-1 biomarkers, including C5DC, exhibited no significant changes in the falsely suspected GA-1 DBS samples. Conversely, 155 endogenous metabolites displayed significant variations compared to the control group. Furthermore, our data identified novel altered metabolic biomarkers, such as N-Palmitoylcysteine, 3-hydroxylinoleoylcarnitine, Heptacarboxyporphyrin, and MG (0:0/20:1/0:0), along with perturbed metabolic pathways like sphingolipid and thiamine metabolism associated with the transient and falsely elevated C5DC levels in DBS samples. Conclusions: Our untargeted metabolomics investigation unveiled distinct metabolic pathways and biomarkers linked to the transient C5DC elevation in DBS samples from falsely suspected GA-1 newborns. These findings can enhance GA-1 diagnosis by serving as predictive indicators during NBS analysis. Validation studies are warranted to confirm the presence of these newly identified metabolic pathways and biomarkers in confirmed GA-1 cases. |
| Institute | King Faisal Specialist Hospital and Research Centre (KFSHRC) |
| Last Name | Al Mogren |
| First Name | Maha |
| Address | Zahrawi Street, Al Maather, Riyadh 11211, Saudi Arabia |
| mahamogren@gmail.com | |
| Phone | 966541205332 |
| Submit Date | 2023-09-11 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Waters) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-04-02 |
| Release Version | 1 |
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Subject:
| Subject ID: | SU003047 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Gender: | Male and female |
