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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).
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Synopsis</h4>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
Journal articleSubject
AlloisoleucineBCKDH
Branched-chain amino acids
Branched-chain ketoacid dehydrogenase deficiency
Isoleucine
Leucine
Lipids
MSUD
Maple syrup urine disease
Metabolomics
Mitochondria
Peroxisomes
Valine
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https://hdl.handle.net/10161/26351Published Version (Please cite this version)
10.1016/j.ymgmr.2020.100651Publication Info
Douglas, Teresa D; Newby, L Kristin; Eckstrand, Julie; Wixted, Douglas; & Singh, Rani
H (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. pp. 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.
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Show full item recordScholars@Duke
Laura Kristin Newby
Professor of Medicine
Research Description General Focus: Clinical investigation the process and treatment
of acute and chronic coronary artery disease and systems issues for delivery of care
to patients with these illnesses. Particular interests include management of patients
with chest pain and unstable angina, evaluation of the use of biochemical markers
other than CK-MB for diagnosis and risk stratification in these patients, issues related
to coronary artery disease in women, and systems issues rega
Douglas Wixted
Research Program Leader, Tier 2
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