Summary of Study ST003792
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
| Study ID | ST003792 |
| Study Title | Untargeted lipidomics characterization of blood samples from patients with maple syrup urine disease (MSUD) in comparison to healthy controls |
| Study Summary | Lipidomics 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: | SU003926 |
| 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 |
|---|---|---|
| SA413021 | AG-88-1 | Healthy control |
| SA413022 | AG-88-2 | Healthy control |
| SA413023 | AG-88-3 | Healthy control |
| SA413024 | AG-88-4 | Healthy control |
| SA413025 | AG-88-5 | Healthy control |
| SA413026 | AG-88-6 | Healthy control |
| SA413029 | AG-88-7 | MSUD |
| SA413030 | AG-88-8 | MSUD |
| SA413031 | AG-88-9 | MSUD |
| SA413027 | AG-88-10 | MSUD with transplant |
| SA413028 | AG-88-11 | MSUD with transplant |
| SA413032 | AG-88-12 | Pool of MSUD with transplant |
| Showing results 1 to 12 of 12 |
Collection:
| Collection ID: | CO003919 |
| 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: | TR003935 |
| Treatment Summary: | No treatment was performed |
Sample Preparation:
| Sampleprep ID: | SP003932 |
| Sampleprep Summary: | Blood aliquots were thawed on ice, then 10 uL of whole blood was treated with with 90 uL of cold methanol. Samples were vortexed 30 min at 4 degrees C then supernatants clarified by centrifugation (10 min, 10,000 g, 4 degrees C) and transferred to autosampler vials. |
| Processing Storage Conditions: | 4℃ |
| Extract Storage: | -80℃ |
Combined analysis:
| Analysis ID | AN006233 | AN006234 |
|---|---|---|
| Chromatography ID | CH004725 | CH004726 |
| MS ID | MS005936 | MS005937 |
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Thermo Vanquish | Thermo Vanquish |
| Column | Phenomenex Kinetex C18 (30 x 2.1mm,1.7um) | Phenomenex Kinetex C18 (30 x 2.1mm,1.7um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
| Ion Mode | NEGATIVE | POSITIVE |
| Units | peak area | peak area |
Chromatography:
| Chromatography ID: | CH004725 |
| Chromatography Summary: | Negative C18 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 (30 x 2.1mm,1.7um) |
| Column Temperature: | 50 |
| Flow Gradient: | 0-3 min 10-95% B at 0.3 mL/min, 3-4.2 min hold at 95% B at 0.3 mL/min, 4.2-4.3 min drop to 10% B at 0.45 mL/min, 4.3-4.9 min hold at 10%B while lowering flow rate to 0.4 mL/min, 4.9-5 min hold at 10%B while lowering flow rate to 0.3 mL/min. |
| Flow Rate: | 0.3 mL/min - 0.45 mL/min |
| Sample Injection: | 10 uL |
| Solvent A: | 75% water/25% acetonitrile; 5 mM ammonium acetate |
| Solvent B: | 90% isopropanol/10% acetonitrile; 5 mM ammonium acetate |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH004726 |
| Chromatography Summary: | Positive C18 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 (30 x 2.1mm,1.7um) |
| Column Temperature: | 50 |
| Flow Gradient: | 0-3 min 30-100% B at 0.3 mL/min, 3-4.2 min hold at 100% B at 0.3 mL/min, 4.2-4.3 min 100-30% B at 0.4 mL/min, 4.3-4.9 min hold at 30%B and 0.4 mL/min, 4.9-5 min hold at 30%B while lowering flow rate to 0.3 mL/min |
| Flow Rate: | 0.3 mL/min - 0.4 mL/min |
| Sample Injection: | 10 uL |
| Solvent A: | 75% water/25% acetonitrile; 5 mM ammonium acetate |
| Solvent B: | 90% isopropanol/10% acetonitrile; 5 mM ammonium acetate |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS005936 |
| Analysis ID: | AN006233 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The Q Exactive was run independently in positive and negative ion mode, scanning using full MS from 125-1500 m/z at 70,000 resolution and top 10 data-dependent MS2 at 17,500 resolution. Electrospray ionization was achieved with 45 Arb sheath gas, 25 Arb auxiliary gas, and 3 kV spray voltage. Calibration was performed prior to the run using the PierceTM Positive and Negative Ion Calibration Solutions (Thermo Fisher Scientific). Run order of samples was randomized and technical replicates were injected after every 4 samples to assess quality control. |
| Ion Mode: | NEGATIVE |
| MS ID: | MS005937 |
| Analysis ID: | AN006234 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The Q Exactive was run independently in positive and negative ion mode, scanning using full MS from 125-1500 m/z at 70,000 resolution and top 10 data-dependent MS2 at 17,500 resolution. Electrospray ionization was achieved with 45 Arb sheath gas, 25 Arb auxiliary gas, and 4 kV spray voltage. Calibration was performed prior to the run using the PierceTM Positive and Negative Ion Calibration Solutions (Thermo Fisher Scientific). Run order of samples was randomized and technical replicates were injected after every 4 samples to assess quality control. |
| Ion Mode: | POSITIVE |
