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).

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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.


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.


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.


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.


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.





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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

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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 regarding optimizing the process of delivery of care to patients with acute and chronic coronary artery disease. Finally, I have a strong interest in defining the genetic contribution to development of coronary artery disease.

Key words: coronary artery disease acute myocardial infarction unstable angina chest pain women biochemical markers risk stratification genetics


Douglas Wixted

Research Program Leader, Sr

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