Mitochondrial encephalomyopathies are multi-system disorders that predominantly affect organs with high ATP consumption such as the brain, the muscles and the sense organs. The phenotypic variation of mitochondrial disorders is large, ranging from migraine and muscle hypotonia to Leigh syndrome, status epilepticus, and death in early childhood. Therefore, even in the best laboratories only 30% of mitochondriopathies can be solved on molecular level. Since the mitochondrial proteins are encoded by two different genomes – the mitochondrial as well as the nuclear DNA – mitochondrial diseases might be inherited in the maternal line or as Mendelian autosomal recessive traits. Therefore careful history taking might considerably narrow down the number of genes to be considered as potentially disease-causing. In some cases the molecular diagnostics can be initiated right away, especially if the physician suspects one of the “classic“ mitochondrial syndromes such as the Kearns-Sayre syndrome or the MERRF and MELAS syndrome. If a suspected mitochondrial disease cannot be grouped under one of these syndromes, a first step would be to perform a muscle biopsy in order to narrow down candidate genes by biochemical measurements. If a deficiency in one of the respiratory chain complexes, the F1F0ATPase or the Pyruvate-dehydrogenase complex (PDHc) can be verified, molecular diagnostics can be applied more specifically by further analysis of the genes encoding functional subunits of the complexes or assembly genes. This presentation aims to guide the physician to find the molecular diagnosis with the help of information from the family history, and from clinical as well as biochemical investigations.
