Summary of project PR001652

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


Project ID: PR001652
Project DOI:doi: 10.21228/M85D90
Project Title:Hydroxylated acylcarnitines as potential biomarkers for VLCADD newborn patients in Saudi Arabia
Project Type:newborn screening
Project 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

Summary of all studies in project PR001652

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002560 Hydroxylated acylcarnitines as potential biomarkers for VLCADD newborn patients in Saudi Arabia Homo sapiens King Faisal Specialist Hospital and Research Centre (KFSHRC) MS* 2023-05-04 1 30 Uploaded data (37.7G)*