title: Impaired cardiac and skeletal muscle bioenergetics in children, adolescents, and young adults with Barth syndrome.
abstract: Barth syndrome (BTHS) is an X-linked condition characterized by altered cardiolipin metabolism and cardioskeletal myopathy. We sought to compare cardiac and skeletal muscle bioenergetics in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardiac function and exercise capacity. Children/adolescents and young adults with BTHS (n= 20) and children/adolescent and young adult control participants (n= 23, totaln= 43) underwent31P magnetic resonance spectroscopy (31P-MRS) of the lower extremity (calf) and heart for estimation of skeletal muscle and cardiac bioenergetics. Peak exercise testing (VO2peak) and resting echocardiography were also performed on all participants. Cardiac PCr/ATP ratio was significantly lower in children/adolescents (BTHS: 1.5 ± 0.2 vs.
  
  
  METHODS
  2.0 ± 0.3,P< 0.01) and adults (BTHS: 1.9 ± 0.2 vs.
  
  
  METHODS
  2.3 ± 0.2,P< 0.01) with BTHS compared to Control groups. Adults (BTHS: 76.4 ± 31.6 vs.
  
  
  METHODS
  35.0 ± 7.4 sec,P< 0.01) and children/adolescents (BTHS: 71.5 ± 21.3 vs.
  
  
  METHODS
  31.4 ± 7.4 sec,P< 0.01) with BTHS had significantly longer calf PCr recovery (τPCr) postexercise compared to controls. Maximal calf ATP production through oxidative phosphorylation (Qmax-lin) was significantly lower in children/adolescents (BTHS: 0.5 ± 0.1 vs.
  
  
  METHODS
  1.1 ± 0.3 mmol/L per sec,P< 0.01) and adults (BTHS: 0.5 ± 0.2 vs.
  
  
  METHODS
  1.0 ± 0.2 mmol/L sec,P< 0.01) with BTHS compared to controls. Blunted cardiac and skeletal muscle bioenergetics were associated with lowerVO2peakbut not resting cardiac function. Cardiac and skeletal muscle bioenergetics are impaired and appear to contribute to exercise intolerance in BTHS.
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.|Department of Electrical and Computer Engineering, Auburn University, Auburn, Alabama.
authors.forename: Adil
authors.initials: A
authors.lastname: Bashir
authors.affiliation: Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Bohnert
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dominic N
authors.initials: DN
authors.lastname: Reeds
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Peterson
authors.affiliation: Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bittel
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Lisa
authors.initials: L
authors.lastname: de las Fuentes
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, Florida.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Pacak
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, Florida.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Byrne
authors.affiliation: Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri tcade@wustl.edu.|Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: W Todd
authors.initials: WT
authors.lastname: Cade
mesh_terms: D000293:Adolescent; D000328:Adult; D056889:Barth Syndrome / Q000378:metabolism*; D004734:Energy Metabolism; D015444:Exercise; D005080:Exercise Test; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D055815:Young Adult
keywords: Barth syndrome; energetics; exercise; mitochondria; muscle