Does the patient have a mitochondrial encephalomyopathy?

The ubiquitous nature of mitochondria, the dual genetic control of the resp iratory chain, and the peculiar rules of mitochondrial genetics contribute to explain the extraordinary clinical heterogeneity of disorders associated with defects of oxidative phosphorylation (mitochondrial encephalomyopathi es). To provide a practical approach to the diagnostic challenge posed by t hese conditions, we critically review the following criteria: (1) clinical presentation; (2) family history; (3) laboratory data; (4) neuroradiologic patterns; (5) standardized exercise testing; (6) muscle morphology; (7) mus cle biochemistry; and (8) molecular genetic screening. Judicious sequential application of these tools should provide help in recognizing patients wit h mitochondrial disease and define the biochemical and molecular basis of t he disorder for each patient. This knowledge is indispensable for accurate genetic counseling and prenatal diagnosis and is a prerequisite for the dev elopment of rational therapies, which are still woefully inadequate.