Lipid changes in the metabolome of a single case study with maple syrup urine disease (MSUD) after five days of improved diet adherence of controlled branched-chain amino acids (BCAA).
Date
2020-12
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Abstract
Background
Distinguishing systemic metabolic disruptions in maple syrup urine disease (MSUD) beyond amino acid pathways is under-investigated, yet important to understanding disease pathology and treatment options.Methods
An adolescent female (15 years) with MSUD without liver transplant, attended 2 study visits, 5 days apart. Medical diet adherence was determined based on her 3-day diet records and plasma branched-chain amino acid (BCAA) concentrations at both study visits. Plasma from a single age- and sex-matched control (MURDOCK Study, Duke University) and the case patient were analyzed with UPLC/MS/MS for intensity (m/z), annotated, and normalized against a median of 1 (Metabolon, Morrisville NC). Differences between case/control and 5-day comparisons were defined as ≥ ǀ 0.5 ǀ.Results
434 lipid metabolites were identified across samples; 90 (20.7%) were higher and 120 (27.6%) lower in the MSUD case at baseline compared with control. By study visit 2, plasma BCAA had declined, while 48 (53%) of elevated lipids and 14 (11.7%) of lower lipid values had moved to within ǀ 0.5 ǀ of control. Most shifts towards control by day 5 were seen in long-chain fatty acid intermediates (42%) and acylcarnitines (32%). Although androgenic (28%) and bile acid (23%) metabolites increased towards control, neither reached control level by day 5.Discussion
This comparative metabolomics study in a single MSUD case and healthy control suggests intrinsic differences in MSUD lipid metabolism potentially influenced by therapeutic diet. Findings suggest influences on hormone regulation, fatty acid oxidation, and bile acid synthesis, but further studies are needed to confirm an association between MSUD and lipid dysregulation.Synopsis
Within 5 days of improved dietary adherence, a single MSUD case experienced substantial changes in lipid markers potentially related to changes in plasma branched-chain amino acids.Type
Department
Description
Provenance
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Douglas, Teresa D, L Kristin Newby, Julie Eckstrand, Douglas Wixted and Rani H Singh (2020). Lipid changes in the metabolome of a single case study with maple syrup urine disease (MSUD) after five days of improved diet adherence of controlled branched-chain amino acids (BCAA). Molecular genetics and metabolism reports, 25. p. 100651. 10.1016/j.ymgmr.2020.100651 Retrieved from https://hdl.handle.net/10161/26351.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Douglas Wixted
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.