We thus instituted a trial of Vitamins C 200 mg twice a day and E 400 IU daily. After 6 months, she had a 6-fold increase in endurance time on sustained deltoid abduction. This supported our speculation that increased oxidative AB1010 VEGFR/PDGFR inhibitor stress is a pathogenetic mechanism in SCADD. Mitochondria are a major site of reactive oxygen species production, which are pathologic when excessive. Mitochondrial dysfunction with increased ROS secondary to SCADD could explain the overlapping clinical features of complex I and SCADD as seen in our patient. The possible association between SCADD and oxidative stress in vitro has been investigated. EMA inhibits mitochondrial creatine kinase activity, increases lipid and protein oxidation products, and decreases glutathione levels in rat cerebral cortex. In human skeletal muscle, EMA inhibits electron transport at complexes I�CIII and II�CIII. Given that the respiratory chain may generate excessive ROS from defective electron transport, at complex I and Complex III, we speculate that EMA accumulation may contribute to oxidative stress and the neurological symptoms in SCADD patients by this mechanism. Furthermore, ROS reportedly affects the permeability of the blood brain barrier, enhancing neuronal vulnerability to ROS toxicity. The second possible mechanism is a direct consequence of the SCAD protein misfolding. The mitochondrial RC produces superoxides or hydroxyl radicals from the interaction of molecular oxygen with semi-quinone or –VE-822 ATM/ATR inhibitor flavone species. SCAD is an FAD-linked dehydrogenase, and a defect in SCAD function, due to misfolding and defective interaction with functional partners e.g. electron transfer flavoprotein, may thus lead to the production of superoxides in proximity to sites of semi-flavone production. A third potential mechanism relates to cellular antioxidant status. Oxidative stress is due to an imbalance between excessive ROS generation and antioxidant capacity, such as superoxide dismutase and glutathione peroxidase activity. The two intracellular SOD enzymes are intramitochondrial manganese superoxide dismutase and cytosolic copper zinc SOD.