Histochemical and Ultrastructural Analysis of the Mitochondrial Changes in a Familial Mitochondrial Myopathy

Two familial cases of progressive external ophthalmoplegia with involvement of pharyngeal and distal muscles are presented. 'Ragged-red' fibres were found in both cases. Excessive amounts of RNA, as evidenced by the acridine orange-induced fluorescence, were noted in many muscle fibres, mostly in the 'ragged-red' fibres. At the ultrastructural level, numerous mitochondrial changes with paracrystalline formations were noted. Those formations were observed in three forms and three-dimensional reconstruction is proposed which suggests that the paracrystalline formations consist of undulating parallel leaflets joined along the top of the undulations. Small transverse bridges between neighbouring cristae and between cristae and paracrystalline formations are also emphasized. All those mitochondrial abnormalities are thought to represent the morphological expression of a biochemical deficiency in the inner membrane. They are interpreted thus: firstly, the biochemical defect leads to a multiplication of the mitochondria with increase in their volume and proliferation of the cristae in order to improve energy production; secondly, bridges between the modified inner membranes induce attachment of the neighbouring cristae and result in paracrystalline formations.