Summary of Study ST003794
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 PR002369. The data can be accessed directly via it's Project DOI: 10.21228/M8DR7V 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 | ST003794 |
| Study Title | Metabolomics characterization of blood samples from patients with maple syrup urine disease (MSUD) in comparison to healthy controls |
| Study Summary | Metabolomics analysis was performed on blood samples from MSUD patients and MSUD patients post-liver transplantation in comparison to healthy controls. |
| Institute | University of Colorado Denver |
| Last Name | Haines |
| First Name | Julie |
| Address | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| julie.haines@cuanschutz.edu | |
| Phone | 3037243339 |
| Submit Date | 2025-03-10 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-06-05 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002369 |
| Project DOI: | doi: 10.21228/M8DR7V |
| Project Title: | Advancing the Biochemical Understanding of Maple Syrup Urine Disease and the impact of liver transplantation: A Pilot Study |
| Project Summary: | Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by impaired catabolism of branched-chain amino acids (BCAAs), leading to severe systemic dysregulation. The disease has an incidence of approximately 1 in 185,000 live births in the general U.S. population, with much higher prevalence in the Mennonite communities (up to 1 in 140 live births in the latter due to the c.1312T>A p.Tyr438Asn BCKDHA founder mutation). Using a multi-omics approach integrating metabolomics, lipidomics, and proteomics, we analyzed blood samples from three MSUD patients on a BCAA-restricted diet, two post-liver transplantation patients, and six healthy controls. Gene ontology analysis highlighted enriched pathways in MSUD, including glycolysis, oxidative phosphorylation, and purine metabolism, revealing systemic metabolic imbalances. Lipidomics indicated disruptions in sphingolipids and lysophosphatidylcholines, which impact cellular signaling and membrane integrity. Liver transplantation corrected some abnormalities, but several metabolites and proteins remained dysregulated. Proteomic analysis revealed significant alterations in redox homeostasis, energy metabolism, and cytoskeletal organization, with only partial recovery post-transplantation. Post-translational modifications, such as methylation and cysteine oxidation, suggested ongoing oxidative stress and immune activation in the LT group. Elevated levels of L-isoleucine, L-valine, and their ketoacids persisted post-transplant, correlating with impaired amino acid metabolism, lipid remodeling, and protein folding. These findings provide comprehensive insight into MSUD-associated metabolic dysfunctions and highlight potential therapeutic targets to improve patient outcomes. |
| Institute: | University of Colorado Denver |
| Laboratory: | Angelo D'Alessandro in collaboration with D. Holmes Morton |
| Last Name: | Haines |
| First Name: | Julie |
| Address: | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| Email: | julie.haines@cuanschutz.edu |
| Phone: | 3037243339 |
Subject:
| Subject ID: | SU003928 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Gender: | Male and female |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Disease state |
|---|---|---|
| SA413045 | AG-88-1 | Healthy control |
| SA413046 | AG-88-2 | Healthy control |
| SA413047 | AG-88-3 | Healthy control |
| SA413048 | AG-88-4 | Healthy control |
| SA413049 | AG-88-5 | Healthy control |
| SA413050 | AG-88-6 | Healthy control |
| SA413053 | AG-88-7 | MSUD |
| SA413054 | AG-88-8 | MSUD |
| SA413055 | AG-88-9 | MSUD |
| SA413051 | AG-88-10 | MSUD with transplant |
| SA413052 | AG-88-11 | MSUD with transplant |
| SA413056 | AG-88-12 | Pool of MSUD with transplant |
| Showing results 1 to 12 of 12 |
Collection:
| Collection ID: | CO003921 |
| Collection Summary: | The study was conducted in accordance with the Declaration of Helsinki; specimens were collected at the Central Pennsylvania Clinic, Boston Children’s Hospital, and Lancaster General Hospitals under institutionally reviewed Protocol No. 2014-12 and upon signing of informed consent. Blood collections were carried out using standard equipment and clinical procedures. To study the metabolic changes occurring in patients with maple syrup urine disease, whole blood was collected from 3 patients having diagnosis of MSUD with a biallelic inactivating mutation of BCKDHA (c.1312T>A p.Tyr438Asn). Additional samples were collected from 6 healthy controls. Finally, samples were collected from two patients having a previous diagnosis of MSUD, but who had received liver transplantations to cure their condition. These two samples were combined 1:1, v:v, to generate a third replicate for statistical analysis. |
| Sample Type: | Blood (whole) |
Treatment:
| Treatment ID: | TR003937 |
| Treatment Summary: | No treatment was performed |
Sample Preparation:
| Sampleprep ID: | SP003934 |
| Sampleprep Summary: | Blood aliquots were thawed on ice, then 10 uL of whole blood was treated with with 90 uL of cold 5:3:2 methanol:acetonitrile:water. Samples were vortexed 30 min at 4 degrees C then supernatants clarified by centrifugation (10 min, 10,000 g, 4 degrees C). For negative ion mode runs, supernatants were transferred to autosampler vials. For positive ion mode runs, 35 uL of extract was dried on a speedvac then resuspended in 35 uL of 0.1% formic acid in water. FA solutions were then transferred to autosampler vials for analysis. |
| Processing Storage Conditions: | 4℃ |
| Extract Storage: | -80℃ |
Chromatography:
| Chromatography ID: | CH004728 |
| Chromatography Summary: | Negative C18 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) |
| Column Temperature: | 45 |
| Flow Gradient: | 0-0.5 min hold at 0% B, 0.5-1.1 min increase to 100% B, 1.1-2.75 min hold at 100% B, 2.75-3 min decrease to 0% B, 3-5 min hold at 0% B |
| Flow Rate: | 0.45 mL/min |
| Sample Injection: | 10 uL |
| Solvent A: | 5% acetonitrile/95% water; 5 mM ammonium acetate |
| Solvent B: | 95% acetonitrile/5% water; 5 mM ammonium acetate |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH004729 |
| Chromatography Summary: | Positive C18 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) |
| Column Temperature: | 45 |
| Flow Gradient: | 0-0.5 min hold at 0% B, 0.5-1.1 min increase to 100% B, 1.1-2.75 min hold at 100% B, 2.75-3 min decrease to 0% B, 3-5 min hold at 0% B |
| Flow Rate: | 0.45 mL/min |
| Sample Injection: | 10 uL |
| Solvent A: | 100% water; 0.1% formic acid |
| Solvent B: | 100% acetonitrile |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN006236 |
| Analysis Type: | MS |
| Chromatography ID: | CH004728 |
| Num Factors: | 4 |
| Num Metabolites: | 77 |
| Units: | peak area |
| Analysis ID: | AN006237 |
| Analysis Type: | MS |
| Chromatography ID: | CH004729 |
| Num Factors: | 4 |
| Num Metabolites: | 126 |
| Units: | peak area |
