Histopathological Diagnosis of Mitochondrial Myopathies - Indications and the Utility of Muscle Biopsy

Mitochondrial myopathies make up a complex heterogenous group of diseases characterized by mitochondrial dysfunction. Mitochondrial disorders are caused biochemically, by impairment of the oxidative phosphorylation system formed by five multi-subunit polypeptide complexes (I-V) located within the inner mitochondrial membrane, along with two electron carriers (Q10 and cytochrome c). The electron carriers and complex II are nuclear DNA-encoded, while the remaining complexes are encoded both by nuclear and mitochondrial DNA. Classification of mitochondrial disorders is rendered complicated by clinical and genetic heterogeneity. Morphological examination is based on evaluation of the general pattern of histopathological changes in a muscle biopsy, of quantitative and qualitative alteration of the mitochondria and, last but not least, on assessment of the presence/absence of ragged red fibres in relation to the cytochrome c oxidase and succinyldehydrogenase reactivity. Combined with immunohistochemistry and in situ hybridisation, this may allow assessment of the type of heredity and/or point to a disorder in a certain complex of the oxidative phosphorylation chain.