Mitochondrial myopathies and the role of the pathologist in the molecular era

Mitochondrial encephalomyopathies are under increasing consideration in the differential diagnosis of diverse metabolic diseases from infancy to late adulthood. This is to be expected considering the vital importance of mitochondria to cellular respiration in all eukaryotes, the vulnerability of the mitochondrial genome to injury, and the expanding appreciation of the role of mitochondria as a common denominator in cell death in ischemia/anoxia, sepsis, and neurodegenerative diseases. Primary disease of the mitochondrial respiratory chain is estimated to occur with an incidence of between 6 and 16/100,000 individuals. Virtually all tissues have been shown to be involved in diverse mitochondriopathies, but none is more appropriate for diagnosis in most cases than skeletal muscle. The conventional histological and ultrastructural diagnosis of mitochondrial disease in muscle has been increasingly supplanted by the biochemical assessment of respiratory chain enzyme deficiencies and definitive genetic diagnosis. The use of such techniques has afforded a greater understanding for the relative lack of specificity of both light and electron microscopic observations. A review of the current situation by placing muscle pathology in the context of biochemical and genetic diagnosis serves as a paradigm for the role of the pathologist in the molecular era.