Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function

Yana Sandlers, Kelly Mercier, Wimal Pathmasiri, Jim Carlson, Susan McRitchie, Susan Sumner, Hilary J. Vernon

Research output: Research - peer-reviewArticle

Abstract

Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects.

LanguageEnglish (US)
Pagese0151802
JournalPloS one
Volume11
Issue number3
DOIs
StatePublished - 2016

Fingerprint

cardiolipins
metabolomics
pathogenesis
metabolites
Cardiolipins
Metabolites
Metabolomics
Barth Syndrome
Metabolism
Amino Acids
neutropenia
fatty acid metabolism
muscular diseases
amino acid metabolism
cardiomyopathy
biogenic amines
lipid metabolism
liquid chromatography
biochemical pathways
nuclear magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function. / Sandlers, Yana; Mercier, Kelly; Pathmasiri, Wimal; Carlson, Jim; McRitchie, Susan; Sumner, Susan; Vernon, Hilary J.

In: PloS one, Vol. 11, No. 3, 2016, p. e0151802.

Research output: Research - peer-reviewArticle

Sandlers Y, Mercier K, Pathmasiri W, Carlson J, McRitchie S, Sumner S et al. Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function. PloS one. 2016;11(3):e0151802. Available from, DOI: 10.1371/journal.pone.0151802
Sandlers, Yana ; Mercier, Kelly ; Pathmasiri, Wimal ; Carlson, Jim ; McRitchie, Susan ; Sumner, Susan ; Vernon, Hilary J./ Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function. In: PloS one. 2016 ; Vol. 11, No. 3. pp. e0151802
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