Indexed on: 31 Mar '19Published on: 30 Mar '19Published in: Journal of Inherited Metabolic Disease
Barth syndrome (BTHS) is a rare X-linked condition resulting in abnormal mitochondria, cardioskeletal myopathy, and growth delay however; the effects of BTHS on substrate metabolism regulation and their relationships with tissue function in humans are unknown. We sought to characterize glucose and fat metabolism during rest, submaximal exercise, and post-exercise rest in children, adolescents and young adults with BTHS and unaffected controls and examine their relationships with cardio-skeletal energetics and function. Children/adolescents and young adults with BTHS (n=29) and children/adolescent and young adult control participants (n=28, total n=57) underwent an infusion of 6'6'H2 glucose and U- C palmitate and indirect calorimetry during rest, 30-minutes of moderate exercise (50% V˙O2peak) and recovery. Cardiac function, cardioskeletal mitochondrial energetics and exercise capacity were examined via echocardiograpy, P magnetic resonance spectroscopy and peak exercise testing, respectively. Glucose turnover rate was significantly higher in individuals with BTHS during rest (33.2 ± 9.8 vs. 27.2 ± 8.1 μmol/kgFFM/min, p<0.01) and exercise (34.7 ± 11.2 vs. 29.5 ± 8.8 μmol/kgFFM/min, p<0.05) and tended to be higher post-exercise (33.7 ± 10.2 vs. 28.8 ± 8.0 μmol/kgFFM/min, p<0.06) compared to Controls. Increases in total fat (-3.9 ± 7.5 vs. 10.5 ± 8.4 μmol/kgFFM/min, p<0.0001) and plasma fatty acid oxidation rates (0.0 ± 1.8 vs. 5.1 ± 3.9 μmol/kgFFM/min, p<0.0001) from rest to exercise were severely blunted in BTHS compared to Controls. Conclusion: An inability to upregulate fat metabolism during moderate intensity exercise appears to be partially compensated by elevations in glucose metabolism. Derangements in fat and glucose metabolism are characteristic of the pathophysiology of BTHS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.