Succinate dehyrodgenase is a critical step in the Krebs cycle and the first component of complex II in the respiratory chain. Several patients have been described with defects involving complex II presenting with a progressive encephalomyopathy. Also reported is a tissue specific combined defect of succinate dehydrogenase and aconitase in skeletal muscle with resulting limb weakness and exercise intolerance. A documented point mutation in a nuclear-encoded subunit represents the first example involving the respiratory chain.