Mutations in complex III-related genes typically manifest as exercise intolerance.  Other mutations have been reported to cause septo-optic dysplasia and multisystem disorders. However, mutations in BCS1L, a gene responsible for proper maturation of complex III, can result in Björnstad syndrome and the GRACILE syndrome, which in neonates are lethal conditions that have multisystem and neurologic manifestations typifying severe mitochondrial disorders. The pathogenicity of several mutations has been verified in model systems such as yeast.
The extent to which these various pathologies are due to bioenergetic deficits or overproduction of superoxide is presently unknown.