Exercise training in metabolic myopathies.

Metabolic myopathies encompass muscle glycogenoses (GSD) and disorders of muscle fat oxidation (FAOD). FAODs and GSDs can be divided into two main clinical phenotypes; those with static symptoms related to fixed muscle weakness and atrophy, and those with dynamic, exercise-related symptoms that are brought about by a deficient supply of ATP. Together with mitochondrial myopathies, metabolic myopathies are unique among muscle diseases, as the limitation in exercise performance is not solely caused by structural damage of muscle, but also or exclusively related to energy deficiency. ATP consumption can increase 50-100-fold in contracting, healthy muscle from rest to exercise, and testing patients with exercise is therefore an appropriate approach to disclose limitations in work capacity and endurance in metabolic myopathies. Muscles rely almost exclusively on muscle glycogen in the initial stages of exercise and at high work intensities. Thus, patients with GSDs typically have symptoms early in exercise, have low peak work capacities and develop painful contractures in exercised muscles. Muscle relies on fat oxidation at rest and to a great extent during prolonged exercise, and therefore, patients with FAODs typically develop symptoms later in exercise than patients with GSDs. Due to the exercise-related symptoms in metabolic myopathies, patients generally have been advised to shun physical training. However, immobility is associated with multiple health issues, and may even cause unwanted metabolic adaptations, such as increased dependence on glycogen use and a reduced capacity for fatty acid oxidation, which is detrimental in GSDs. Training has not been studied systematically in any FAODs and in just a few GSDs. However, studies on single bouts of exercise in most metabolic myopathies show that particularly moderate intensity aerobic exercise is well tolerated in these conditions. Even low-intensity resistance training of short duration is tolerated in McArdle disease. Training in patients with FAOD potentially can also expand the metabolic bottleneck by increasing expression of the defective, but partially functional enzyme. Exercise performance in metabolic myopathies can be improved by different fuel supplementations and dietary interventions and should be considered as adjunct therapy to exercise training.