Summary of Study ST003171

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 PR001971. The data can be accessed directly via it's Project DOI: 10.21228/M8Z72R 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.

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Study IDST003171
Study TitleUntargeted Metabolomics for Exploring Metabolomic Profile of Maple Syrup Urine Disease Sick Patients
Study TypeUntargeted LCMS
Study SummaryAbstract non-newborn: Background: A malfunction in the activity of the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex results in maple syrup urine disease (MSUD), a genetically inherited illness. Three amino acids—leucine, isoleucine, and valine—are typically broken down by this complex. Abnormal activity in this process, therefore, can affect vital body systems and result in metabolic dysregulation associated with the consequences of the disease. The therapy and follow-up of ill MSUD patients are greatly aided by many researched endogenous metabolites as well as dysregulated biomarkers and pathways. Objectives: Our goal is to add to the increasing knowledge of information about sick MSUD with relation to MSUD newborns and the pathways that are involved in improving patient outcomes by utilizing untargeted metabolomics to examine the unique profile of MSUD in sick MSUD patients. Methods: This study evaluated the metabolic changes in the dry blood spot (DBS) of 14 sick MSUD patients and 14 healthy controls utilizing untargeted metabolomics studies performed with liquid chromatography–mass spectrometry. Findings: Based on metabolomics analysis,7754 metabolites were found to be highly dysregulated.Out of them,3716 were up-regulated and 4038 were down-regulated.1557 of the annotated metabolites were found to be endogenous metabolites. The research found possible biomarkers for MSUD, including Glutathioselenol and dUDP, which were elevated in sick MSUD relative to healthy controls and LysoPI downregulated in sick MSUD. Moreover, the Sphingolipid metabolism, selenocompound metabolism and porphyrin metabolism pathways were the most impacted in MSUD newborns.This study shows 92 endogenous metabolites between newborn MSUD and sick MSUD. In summary, our findings shows that metabolomics is a noninvasive approach to understanding the pathophysiology of the medical condition and a potentially useful technique for assessing novel biomarkers in the early detection of sick MSUD.Further research is required regarding the relationship of these dysregulated metabolites to compromised pathways.
Institute
King Saud University
DepartmentBiochemistry
LaboratoryClinical Biochemistry
Last NameAlOtaibi
First NameAbeer
Address2808
Email441203289@student.ksu.edu.sa
Phone+966551933703
Submit Date2023-12-09
Num Groups2
Total Subjects28
Num Males7
Num Females7
Raw Data AvailableYes
Raw Data File Type(s)raw(Waters)
Analysis Type DetailLC-MS
Release Date2024-04-29
Release Version1
Abeer AlOtaibi Abeer AlOtaibi
https://dx.doi.org/10.21228/M8Z72R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001971
Project DOI:doi: 10.21228/M8Z72R
Project Title:Comberhincive Chemometric Metabolomic Profile for Maple Syrup Urine Disease Sick Patients
Project Type:Untargeted LCMS
Project Summary:Abstract: Background: A malfunction in the activity of the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex results in maple syrup urine disease (MSUD), a genetically inherited illness. Three amino acids—leucine, isoleucine, and valine—are typically broken down by branched-chain alpha-keto acid dehydrogenase complex. Abnormal activity in this process, therefore, can affect vital body systems and result in metabolic dysregulation associated with the consequences of this disease. The therapy and follow-up of ill MSUD patients are greatly aided by many researched endogenous metabolites as well as dysregulated biomarkers and pathways. Objectives: Our goal is to add to the increasing knowledge of information about sick MSUD and the pathways that are involved in improving patient outcomes by utilizing untargeted metabolomics to examine the unique profile of MSUD in sick MSUD patients. Methods: This study evaluated the metabolic changes in the dry blood spot (DBS) of 14 sick MSUD patients and 14 healthy controls utilizing untargeted metabolomics studies performed with liquid chromatography–mass spectrometry. Findings: Based on metabolomics analysis,7754 metabolites were found to be highly dysregulated.Out of them,3716 were up-regulated and 4038 were down-regulated.1557 of the annotated metabolites were found to be endogenous metabolites. The research found possible biomarkers for MSUD, including Glutathioselenol and dUDP, which were elevated in sick MSUD relative to healthy controls and LysoPI downregulated in sick MSUD. Moreover, the Sphingolipid metabolism, selenocompound metabolism and porphyrin metabolism pathways were the most impacted in sick MSUD. In summary, our findings shows that metabolomics is a noninvasive approach to understanding the pathophysiology of the medical condition and a potentially useful technique for assessing novel biomarkers in the early detection of sick MSUD.Further research is required regarding the relationship of these dysregulated metabolites to compromised pathways.
Institute:King Saud University
Department:Biochemistry
Laboratory:Clinical Biochemistry
Last Name:AlOtaibi
First Name:Abeer
Address:King Fahad road,Riyadh 11211, Saudi Arabia
Email:441203289@student.ksu.edu.sa
Phone:+966551933703

Subject:

Subject ID:SU003290
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:>14 days,
Gender:Male and female
Human Inclusion Criteria:>14 days, MSUD sick patients DBS
Human Exclusion Criteria:</=14 days, any IEM's sick other than MSUD, unknown gender
Species Group:Mammals

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Sex sample_type
SA34307621695964F Control
SA34307721799570F Control
SA34307821800326F Control
SA34307921489309F Control
SA34308021796397F Control
SA34308121489196F Control
SA34308220839516F Control
SA34308321273683F Control
SA34308421805181F MSUD
SA34308521100943F MSUD
SA34308621460012F MSUD
SA34308721799172F MSUD
SA34308820613149F MSUD
SA34308921770104F MSUD
SA34309027339556F MSUD
SA34309120820068M Control
SA34309221532106M Control
SA34309321489947M Control
SA34309420830764M Control
SA34309521581573M Control
SA34309620830816M Control
SA34309721833519M MSUD
SA34309821914504M MSUD
SA343099148705M MSUD
SA34310015383554M MSUD
SA34310121219108M MSUD
SA34310221776205M MSUD
SA34310321796944M MSUD
Showing results 1 to 28 of 28

Collection:

Collection ID:CO003283
Collection Summary:Twenty-eight DBS samples were collected from biochemically and genetically confirmed MSUD sick patients (n=14) at King Faisal Specialist Hospital and Research Center (KFSHRC) and healthy controls (n=14). These healthy individuals were almost age-sex matched with MSUD's group (Female 50%). Samples from newborn patients and controls less than 14 days were excluded from this study, as well as any IEM other than MSUD excluded.
Sample Type:Blood (whole)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003299
Treatment Summary:No treatment used.

Sample Preparation:

Sampleprep ID:SP003297
Sampleprep Summary:One punch, of size 3.3mm, DBS from MSUD newborn and healthy controls were distributed in 96 V-shaped plate wells, then immersed with 250 μL of extraction solvent composed of 20% Water: 20% MeOH:40% ACN. The samples were vortexed in thermomixer (Eppendrof, Germany) at 600 rpm, 25˚C, for 2hrs. The samples were spun down at 16.000 rpm, 4˚C, for 10 min. The supernatants were transferred into new 96 V-shaped plate and the punches discarded, and then the samples were dried in a vacuum concentrator SpeedVac (Christ, City, Germany). Dry residue was re-dissolved in 100 μL of methanol/water with a ratio (1:1) prior to LC-MS analysis.
Sampleprep Protocol Filename:MSUD_Metabolites_Extraction.pdf
Processing Storage Conditions:Room temperature
Extract Storage:Room temperature

Chromatography:

Chromatography ID:CH003938
Methods Filename:MSUD_LC_MS_Metabolomics.pdf
Instrument Name:Waters Acquity UPLC
Column Name:Waters XSelect CSH C18 (100 x 2.1mm 2.5um)
Column Temperature:55
Flow Gradient:95–5% A [0–16 min], 5% A [16–19 min], 5–95% A [19–20 min], and 95–95% A [20–22 min].
Flow Rate:300 μL/min
Solvent A:100% water; 0.1% formic acid
Solvent B:50% MeOH/50% ACN; 0.1% formic acid
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN005204
Analysis Type:MS
Analysis Protocol File:Metabolomics_Pos_and_Neg.pdf
Chromatography ID:CH003938
Has Mz:1
Has Rt:1
Rt Units:Seconds
Results File:ST003171_AN005204_Results.txt
Units:Peak area
  
Analysis ID:AN005205
Analysis Type:MS
Analysis Protocol File:Metabolomics_Pos_and_Neg.pdf
Chromatography ID:CH003938
Has Mz:1
Has Rt:1
Rt Units:Seconds
Results File:ST003171_AN005205_Results.txt
Units:Peak area
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