The value of mitochondrial DNA analysis in clinical practice

Mitochodrial disorders are being increasingly recognized in clinical practice and are frequently considered in the differential diagnosis of various symptoms. Interpretation of the usual laboratory methods for the recognition of the impairment of oxidative metabolism, such as the measurements of lactic acid, pyruvates, ketonic bodies and some organic acids is complicated due to their natural variability and limited specificity. More specific tests for the determination of the activity of mitochondrial enzymes and other mitochondrial proteins are not commonly available and their implementation often encounters logistic problems, such as the transportation of frozen tissues to specialized laboratories abroad. Therefore, molecular analysis of genes responsible for the coding of the mitochondrial proteins has become an important and convenient diagnostic tool. Analysis of the nuclear genes, coding a major proportion of the proteins involved in mitochondrial energy production, is mainly indicated in patients with well-defined biochemical disorders. Analysis of the mitochondrial DNA (mtDNA), however, is indicated on the basis of clinical findings combined with laboratory evidence of impaired oxidative metabolism, as detected by common biochemical parameters (eg. lactacidosis). This paper presents a short account of clinical and laboratory indications for the analysis of the mitochondrial DNA, the expression and the type of mtDNA mutations and the methods for their detection.