Summary of project PR002369
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
| 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 |
Summary of all studies in project PR002369
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003792 | Untargeted lipidomics characterization of blood samples from patients with maple syrup urine disease (MSUD) in comparison to healthy controls | Homo sapiens | University of Colorado Denver | MS | 2025-06-05 | 1 | 12 | Uploaded data (927.4M)* |
| ST003793 | Oxylipins in blood samples from patients with maple syrup urine disease (MSUD) in comparison to healthy controls | Homo sapiens | University of Colorado Denver | MS | 2025-06-05 | 1 | 12 | Uploaded data (1.3G)* |
| ST003794 | Metabolomics characterization of blood samples from patients with maple syrup urine disease (MSUD) in comparison to healthy controls | Homo sapiens | University of Colorado Denver | MS | 2025-06-05 | 1 | 12 | Uploaded data (2.1G)* |
