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 |
Select appropriate tab below to view additional metadata details:
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Factor |
|---|---|---|
| SA318308 | 20830117_C | Control |
| SA318309 | 20820305_C | Control |
| SA318310 | 20809384_C | Control |
| SA318311 | 20830418_C | Control |
| SA318312 | 20818595_C | Control |
| SA318313 | 20851147_C | Control |
| SA318314 | 20859945_C | Control |
| SA318315 | 20859015_C | Control |
| SA318316 | 20851217_C | Control |
| SA318317 | 20808613_C | Control |
| SA318318 | 20839215_C | Control |
| SA318319 | 20808598_C | Control |
| SA318320 | 20688815_C | Control |
| SA318321 | 20688684_C | Control |
| SA318322 | 20649302_C | Control |
| SA318323 | 20419817_C | Control |
| SA318324 | 20771984_C | Control |
| SA318325 | 20799041_C | Control |
| SA318326 | 20859954_C | Control |
| SA318327 | 20799980_C | Control |
| SA318328 | 20799892_C | Control |
| SA318329 | 20799050_C | Control |
| SA318330 | 20808604_C | Control |
| SA318331 | 20864956_C | Control |
| SA318332 | 21554366_C | Control |
| SA318333 | 21554348_C | Control |
| SA318334 | 21501966_C | Control |
| SA318335 | 21492242_C | Control |
| SA318336 | 21558089_C | Control |
| SA318337 | 21610033_C | Control |
| SA318338 | 21753462_C | Control |
| SA318339 | 21703814_C | Control |
| SA318340 | 21670026_C | Control |
| SA318341 | 21610051_C | Control |
| SA318342 | 21484386_C | Control |
| SA318343 | 21462162_C | Control |
| SA318344 | 20902618_C | Control |
| SA318345 | 20890216_C | Control |
| SA318346 | 20884792_C | Control |
| SA318347 | 20882846_C | Control |
| SA318348 | 20940654_C | Control |
| SA318349 | 20975067_C | Control |
| SA318350 | 21077520_C | Control |
| SA318351 | 21073931_C | Control |
| SA318352 | 21027899_C | Control |
| SA318353 | 19534501_C | Control |
| SA318354 | 19281533_C | Control |
| SA318355 | 20407797_GA | GA |
| SA318356 | 20334941_GA | GA |
| SA318357 | 20312851_GA | GA |
| SA318358 | 20310303_GA | GA |
| SA318359 | 20488455_GA | GA |
| SA318360 | 20492412_GA | GA |
| SA318361 | 20639226_GA | GA |
| SA318362 | 20624808_GA | GA |
| SA318363 | 20537584_GA | GA |
| SA318364 | 20525109_GA | GA |
| SA318365 | 20308928_GA | GA |
| SA318366 | 20249546_GA | GA |
| SA318367 | 19762935_GA | GA |
| SA318368 | 19568043_GA | GA |
| SA318369 | 19558785_GA | GA |
| SA318370 | 19533094_GA | GA |
| SA318371 | 19785967_GA | GA |
| SA318372 | 19844611_GA | GA |
| SA318373 | 20249412_GA | GA |
| SA318374 | 19929105_GA | GA |
| SA318375 | 19885751_GA | GA |
| SA318376 | 19864732_GA | GA |
| SA318377 | 20735858_GA | GA |
| SA318378 | 20749860_GA | GA |
| SA318379 | 21437087_GA | GA |
| SA318380 | 21371994_GA | GA |
| SA318381 | 21368884_GA | GA |
| SA318382 | 21355783_GA | GA |
| SA318383 | 21443088_GA | GA |
| SA318384 | 21444935_GA | GA |
| SA318385 | MOH00027361087_GA | GA |
| SA318386 | MOH00027354847_GA | GA |
| SA318387 | MOH00027340288_GA | GA |
| SA318388 | MOH00027337062_GA | GA |
| SA318389 | 21349010_GA | GA |
| SA318390 | 21294251_GA | GA |
| SA318391 | 20788142_GA | GA |
| SA318392 | 20780043_GA | GA |
| SA318393 | 20777340_GA | GA |
| SA318394 | 20774404_GA | GA |
| SA318395 | 20830630_GA | GA |
| SA318396 | 20854922_GA | GA |
| SA318397 | 21033438_GA | GA |
| SA318398 | 20927291_GA | GA |
| SA318399 | 20876340_GA | GA |
| SA318400 | 20855976_GA | GA |
| SA318401 | 18862900_GA | GA |
| Showing results 1 to 94 of 94 |
