Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri.
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
J Inherit Metab Dis. 2019 May;42(3):480-493. doi: 10.1002/jimd.12094. Epub 2019 Apr 11.
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 postexercise rest in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardioskeletal 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% ), and recovery. Cardiac function, cardioskeletal mitochondrial energetics, and exercise capacity were examined via echocardiography, P magnetic resonance spectroscopy, and peak exercise testing, respectively. The 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 < .01) and exercise (34.7 ± 11.2 vs 29.5 ± 8.8 μmol/kgFFM/min, P < .05) and tended to be higher postexercise (33.7 ± 10.2 vs 28.8 ± 8.0 μmol/kgFFM/min, P < .06) compared to controls. Increases in total fat (-3.9 ± 7.5 vs 10.5 ± 8.4 μmol/kgFFM/min, P < .0001) and plasma fatty acid oxidation rates (0.0 ± 1.8 vs 5.1 ± 3.9 μmol/kgFFM/min, P < .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. A severely blunted ability to upregulate fat metabolism during a modest level of physical activity is a defining pathophysiologic characteristic in children, adolescents, and young adults with BTHS.
巴德综合征（Barth syndrome）是一种罕见的 X 连锁疾病，导致异常的线粒体、心脏骨骼肌病和生长迟缓；然而，Barth 综合征对底物代谢调节的影响及其与人类组织功能的关系尚不清楚。我们旨在描述患有 Barth 综合征的儿童、青少年和年轻成年人以及未受影响的对照者在休息、亚最大强度运动和运动后恢复期的葡萄糖和脂肪代谢，并检查它们与心脏骨骼能量学和功能的关系。29 名患有 Barth 综合征的儿童/青少年和年轻成年人（n=29）和 28 名儿童/青少年和年轻成年人对照者（n=28，总 n=57）接受了 6'6'H2 葡萄糖和 U- C 棕榈酸输注，并在休息、30 分钟中等强度运动（50%）和恢复期间进行间接测热法。通过超声心动图、P 磁共振波谱和峰值运动测试分别检查心脏功能、心脏骨骼线粒体能量学和运动能力。与对照组相比，Barth 综合征患者在休息时（33.2±9.8 比 27.2±8.1 μmol/kgFFM/min，P<.01）和运动时（34.7±11.2 比 29.5±8.8 μmol/kgFFM/min，P<.05）以及运动后恢复时（33.7±10.2 比 28.8±8.0 μmol/kgFFM/min，P<.06）的葡萄糖周转率明显更高。与对照组相比，总脂肪（-3.9±7.5 比 10.5±8.4 μmol/kgFFM/min，P<.0001）和血浆脂肪酸氧化率（0.0±1.8 比 5.1±3.9 μmol/kgFFM/min，P<.0001）从休息到运动时的增加严重受到抑制。结论：在中等强度运动期间，无法上调脂肪代谢似乎部分由葡萄糖代谢的升高来补偿。脂肪和葡萄糖代谢的紊乱是 Barth 综合征病理生理学的特征。在适度的体力活动期间，上调脂肪代谢的能力严重受损是儿童、青少年和年轻成年人 Barth 综合征的一个明确的病理生理特征。
