In this respect, regular endurance exercise is known to be a potent stimulus for muscle mitochondrial biogenesis (10), and in fact previous research has shown that endurance-based exercise interventions can increase the muscle oxidative capacity of patients with MD, as directly reflected by increases in the activity of citrate synthase (CS) and respiratory chain complexes in skeletal muscle biopsies (11–13), or indirectly, by improvements in patients' aerobic fitness (11–18). Here, CS is linked to Menkes disease.