Madsen Karen L, Preisler Nicolai, Buch Astrid E, Stemmerik Mads G, Laforêt Pascal, Vissing John
Copenhagen Neuromuscular Center, Department of Neurology Copenhagen Neuromuscular Center, Rigshospitalet Copenhagen Denmark.
Neuromuscular Center, Department of Neurology, Neuromuscular Center Raymond-Poincaré Hospital Garches France.
JIMD Rep. 2019 Mar 14;46(1):79-84. doi: 10.1002/jmd2.12024. eCollection 2019 Mar.
We investigated the in vivo skeletal muscle metabolism in patients with multiple acyl-CoA dehydrogenase deficiency (MADD) during exercise, and the effect of a glucose infusion. Two adults with MADD on riboflavin and l-carnitine treatment and 10 healthy controls performed an incremental exercise test measuring maximal oxidative capacity (VO) and a submaximal exercise test (≤1 hour) on a cycle ergometer. During submaximal exercise, we studied fat and carbohydrate oxidation, using stable isotope tracer methodology and indirect calorimetry. On another day, the patients repeated the submaximal exercise receiving a 10% glucose infusion. The patients had a lower VO than controls and stopped the submaximal exercise test at 51 and 58 minutes due to muscle pain and exhaustion. The exercise-induced increase in total fatty acid oxidation was blunted in the patients (7.1 and 1.1 vs 12 ± 4 μmol × kg × min in the healthy controls), but total carbohydrate oxidation was higher (67 and 63 vs 25 ± 11 μmol × kg × min in controls). With glucose infusion, muscle pain decreased and average heart rate during exercise dropped in both patients from 124 to 119 bpm and 138 to 119 bpm. We demonstrate that exercise intolerance in MADD-patients relates to an inability to increase fat oxidation appropriately during exercise, which is compensated partially by an increase in carbohydrate metabolism.
我们研究了多酰基辅酶A脱氢酶缺乏症（MADD）患者运动期间的体内骨骼肌代谢以及葡萄糖输注的影响。两名接受核黄素和左旋肉碱治疗的MADD成年患者以及10名健康对照者进行了递增运动试验，以测量最大氧化能力（VO），并在自行车测力计上进行了次最大运动试验（≤1小时）。在次最大运动期间，我们使用稳定同位素示踪方法和间接量热法研究了脂肪和碳水化合物的氧化。在另一天，患者重复次最大运动并接受10%的葡萄糖输注。患者的VO低于对照组，由于肌肉疼痛和疲劳，分别在51分钟和58分钟时停止了次最大运动试验。患者运动诱导的总脂肪酸氧化增加受到抑制（分别为7.1和1.1，而健康对照组为12±4μmol×kg×min），但总碳水化合物氧化更高（分别为67和63，而对照组为25±11μmol×kg×min）。输注葡萄糖后，两名患者的肌肉疼痛均减轻，运动期间的平均心率从124次/分钟降至119次/分钟，从138次/分钟降至119次/分钟。我们证明，MADD患者的运动不耐受与运动期间无法适当增加脂肪氧化有关，这部分通过碳水化合物代谢的增加得到补偿。
