Journal of Inherited Metabolic Disease

, Volume 36, Issue 1, pp 91–101 | Cite as

Substrate metabolism during basal and hyperinsulinemic conditions in adolescents and young-adults with Barth syndrome

  • W. Todd Cade
  • Carolyn T. Spencer
  • Dominic N. Reeds
  • Alan D. Waggoner
  • Robert O’Connor
  • Melissa Maisenbacher
  • Jan R. Crowley
  • Barry J. Byrne
  • Linda R. Peterson
Original Article



Barth syndrome (BTHS) is a rare X-linked disorder that is characterized by mitochondrial abnormalities, infantile or childhood onset of cardioskeletal myopathy, and high mortality rates. It is currently unknown if BTHS related mitochondrial dysfunction results in substrate metabolism abnormalities and thereby contributes to cardioskeletal myopathy in patients with BTHS.


Adolescents and young adults with BTHS (n = 5, 20 ± 4 yrs) and age and activity matched healthy controls (n = 5, 18 ± 4 yrs) underwent an hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracers for measurement of lipolysis, fatty acid oxidation, glucose disposal, and whole-body proteolysis rates; dual energy x-ray absorptiometry for measurement of body composition and 2-D and strain echocardiography for measurement of left ventricular function.


Participants with BTHS had lower fat-free mass (FFM) (BTHS: 31.4 ± 6.9 vs. Control: 46.7 ± 5.3 kg, p < 0.005), lower systolic function (strain, BTHS: -15.2 ± 2.4 vs. Control: −19.0 ± 2.4 %, p < 0.05), greater insulin-stimulated glucose disposal rate per kg FFM (BTHS: 96.5 ± 16.3 vs. Control: 67.4 ± 17.6 μmol/kgFFM/min, p < 0.05), lower basal (BTHS: 4.6 ± 2.7 vs. Control: 11.9 ± 4.4 μmol/kgFM/min, p < 0.05) and hyperinsulinemic (BTHS: 1.6 ± 0.4 vs. Control: 3.6 ± 1.6 μmol/kgFM/min, p < 0.05) lipolytic rate per kg fat mass (FM), and a trend towards higher basal leucine rate of appearance per kg FFM (BTHS: 271.4 ± 69.3 vs. Control: 193.1 ± 28.7 μmol/kgFFM/hr, p = 0.07) compared to controls. Higher basal leucine rate of appearance per kg FFM (i.e. whole-body proteolytic rate) tended to be associated with lower left ventricular systolic strain (r = −0.57, p = 0.09).


Whole-body fatty acid, glucose and amino acid metabolism kinetics when expressed per unit of body composition are altered and appear to be related to cardioskeletal myopathy in humans with BTHS. Further studies examining myocardial substrate metabolism and whole-body substrate metabolism during increased energy demands (e.g., exercise) and their relationships to skeletal and cardiac function are recommended.


Fatty Acid Oxidation Barth Syndrome Lipolytic Rate Serum Free Fatty Acid Level Hyperinsulinemic Condition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This project was supported by the Barth Syndrome Foundation and by National Institutes of Health grants DK074343 to WTC, DK056341, Institute of Clinical and Translational Sciences (UL1 RR024992), Diabetes Research and Training Center (DK-020579), Biomedical Mass Spectrometry Research Laboratory (RR-000954) and Nutrition-Obesity Research Center (DK-056341) from the National Center for Research Resources (NCRR) and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH or its Institutes.


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Copyright information

© SSIEM and Springer 2012

Authors and Affiliations

  • W. Todd Cade
    • 1
  • Carolyn T. Spencer
    • 2
  • Dominic N. Reeds
    • 3
  • Alan D. Waggoner
    • 4
  • Robert O’Connor
    • 5
  • Melissa Maisenbacher
    • 6
  • Jan R. Crowley
    • 7
  • Barry J. Byrne
    • 6
  • Linda R. Peterson
    • 4
  1. 1.Program in Physical Therapy & Department of MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Division of Pediatric CardiologyEast Carolina University School of MedicineGreenevilleUSA
  3. 3.Division of Geriatrics and Nutritional SciencesWashington University School of MedicineSt. LouisUSA
  4. 4.Cardiovascular DivisionWashington University School of MedicineSt. LouisUSA
  5. 5.Department of RadiologyWashington University School of MedicineSt. LouisUSA
  6. 6.Departments of Pediatrics, Molecular Genetics & MicrobiologyUniversity of FloridaGainesvilleUSA
  7. 7.Division of Endocrinology, Metabolism and Lipid ResearchWashington University School of MedicineSt. LouisUSA

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