Summary of Study ST002560
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 PR001652. The data can be accessed directly via it's Project DOI: 10.21228/M85D90 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 | ST002560 |
| Study Title | Hydroxylated acylcarnitines as potential biomarkers for VLCADD newborn patients in Saudi Arabia |
| Study Summary | Very long acylcarnitine dehydrogenase deficiency (VLCADD) is an inherited metabolic disorder related to fatty acid β-oxidation. It is characterized by genetic mutations in ACADVL gene and accumulations of acylcarnitines. VLCADD can be developed in the neonatal period or during adulthood. Certain diagnostic approaches are used to confirm the diagnosis of VLCADD including genetic sequencing and newborn bloodspot screening (NBS). The last two approaches have shown some limitations such as VUS with genetic sequencing and false positive or negative results in NBS. Therefore, there are demands for additional diagnostic tools for VLCADD. Since VLCADD is associated with disrupted metabolism, untargeted metabolomics, which is an analytical technique used to detect a large-scale profiling of metabolites in biological samples, could be a useful tool for diagnosis. We hypothesized that VLCADD newborns patients may exhibit a unique metabolic profile and biomarkers compared to healthy newborns. Untargeted metabolomics approach was conducted using liquid chromatography-mass spectrometry (LC-MS) to measure the global metabolites in DBS cards collected from VLCADD newborns (n=15) and healthy controls (n=15). Metabolite extraction was performed and followed by LC-MS analysis. Multivariate and univariate analyses were used to analyze the metabolomics data, and pathway and biomarker analyses were also performed on the significantly endogenous identified metabolites. A moderate T-test was used for statistical analysis with no correction, and the cutoff was (p-value ≤ 0.05 and Fold Change 1.5). VLCADD newborns had 2012 significantly dysregulated metabolites compared to healthy newborns. 58 endogenous metabolites were upregulated while 148 endogenous metabolites were downregulated. Pathway analyses showed phenylalanine, tyrosine, and tryptophan biosynthesis as the most affected pathway. Potential metabolic biomarker for VLCADD was 3,4-dihydroxytetradecanoylcarnitine with an area under the curve (AUC) of 1, was in the top-15 biomarker list with the highest p-value and FC, suggesting its high possibility to be used for diagnosis. However, validation experiments of the biomarker is needed in following-up studies to ensure its accuracy and reliability to be used as a VLCADD marker in the clinical practice. |
| Institute | King Faisal Specialist Hospital and Research Centre (KFSHRC) |
| Last Name | AlMalki |
| First Name | Reem |
| Address | Zahrawi Street, Al Maather, Riyadh 11211, Saudi Arabia |
| 439203044@student.ksu.edu.sa | |
| Phone | 0534045397 |
| Submit Date | 2023-04-11 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Waters) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-05-04 |
| Release Version | 1 |
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Sample Preparation:
| Sampleprep ID: | SP002667 |
| Sampleprep Summary: | The metabolites were extracted as reported before with modification (43). In detail, one punch, a size of 3.2 mm, was collected from each DBS sample and transferred into a 96-well plate for metabolite extraction. Metabolite extraction was performed by adding 250 ul extraction solvent (20:40:40) (H2O: ACN: MeOH) to each well with agitation for 2 hours at room temperature. Subsequently, sample extracts were dried using SpeedVac (Thermo Fischer, Christ, Germany). The dried samples were reconstituted in 100 ul of 50% A: B mobile phase. (A: 0.1% Formic acid in H2O, B: 0.1% FA in 50% ACN: MeOH). Additional punches were taken for quality control (QC) from the project samples to maintain the instrument performance. |
| Sampleprep Protocol Filename: | Metabolites_Extraction.docx |
