Impaired cardiac and skeletal muscle bioenergetics in children, adolescents, and young adults with Barth syndrome

Barth syndrome () 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 and unaffected controls and examine their relationships with cardiac function and exercise capacity. Children/adolescents and young adults with ( = 20) and children/adolescent and young adult control participants ( = 23, total  = 43) underwent P magnetic resonance spectroscopy (P‐) of the lower extremity (calf) and heart for estimation of skeletal muscle and cardiac bioenergetics. Peak exercise testing () and resting echocardiography were also performed on all participants. Cardiac r/ ratio was significantly lower in children/adolescents (: 1.5 ± 0.2 vs. Control: 2.0 ± 0.3,  < 0.01) and adults (: 1.9 ± 0.2 vs. Control: 2.3 ± 0.2,  < 0.01) with compared to Control groups. Adults (: 76.4 ± 31.6 vs. Control: 35.0 ± 7.4 sec,  < 0.01) and children/adolescents (: 71.5 ± 21.3 vs. Control: 31.4 ± 7.4 sec,  < 0.01) with had significantly longer calf r recovery (r) postexercise compared to controls. Maximal calf production through oxidative phosphorylation (Qmax‐lin) was significantly lower in children/adolescents (: 0.5 ± 0.1 vs. Control: 1.1 ± 0.3 mmol/L per sec,  < 0.01) and adults (: 0.5 ± 0.2 vs. Control: 1.0 ± 0.2 mmol/L sec,  < 0.01) with compared to controls. Blunted cardiac and skeletal muscle bioenergetics were associated with lower O but not resting cardiac function. Cardiac and skeletal muscle bioenergetics are impaired and appear to contribute to exercise intolerance in BTHS.

Duke Scholars

Author William Todd Cade Orthopaedic Surgery, Physical Therapy