Impaired Fat Metabolism During Exercise in Patients With Methylmalonic and Propionic Acidemia

ABSTRACT Methylmalonic acidemia (MMA) and propionic acidemia (PA) are inherited metabolic diseases causing deficiency in the catabolism of amino acids, cholesterol, and odd‐chain fatty acids. Both patient groups report exercise intolerance and fatigue. We recently reported findings of impaired lipolysis and blunted fat oxidation during exercise in a patient with PA, suggesting a metabolic myopathy phenotype. To further investigate this phenomenon, we conducted a new study to investigate fat and glucose metabolism during exercise in patients with PA and MMA. We included two patients with MMA and two with PA. The patients performed a low‐intensity exercise test on a cycle ergometer, working at a workload corresponding to 50% of their maximal oxygen capacity. Fat and glucose metabolism were quantified at rest and during exercise via continuous infusion of stable isotope‐labeled glucose and palmitate, and indirect calorimetry. The results were compared to those of matched healthy controls. Lipolysis and fatty acid oxidation were close to normal at rest, but impaired during exercise in the patients vs. healthy controls exercising at the same absolute workload: Lipolytic rate (1.5 ± 0.6 vs. 4.0 ± 1.4 μmol kg −1 min −1 , p = 0.001) and palmitate oxidation (0.8 ± 0.6 vs. 2.1 ± 1.0 μmol kg −1 min −1 , p = 0.018). To compensate, the patients increased carbohydrate oxidation (68.2 ± 18.1 vs. 44.9 ± 16.4 μmol kg −1 min −1 ). Our findings indicate that both PA and MMA should be considered metabolic myopathies, which may explain the reported exercise intolerance and fatigue.