Biochemical diagnostics of mitochondrial encephalomyopathies

The laboratory diagnostics of defects of the mitochondrial energy metabolism using body fluids (blood, serum, CSF or urine) is limited and restricted to only few indicative parameters. Most of these parameters are unspecific. Therefore, the cases in which a definite diagnosis can be assigned on the basis of laboratory findings in combination with the disease history and clinical signs are rare. Moreover, neuroimaging methods like NMRI and CT-scans often show unspecific pattern of alterations and even morphological investigations of tissues samples are often not able to differentiate between primary and secondary alterations in either case. In order to establish an unambiguous and distinct diagnosis it is therefore in many cases essential to detect the biochemical defect by measuring the mitochondrial enzyme activities and metabolites. In particular, respiratory chain (RC) deficiencies which cause a significant portion of the mitochondrial encephalomyopathies in children require the direct measurement of the activities of the RC complexes in muscle tissue homogenates or the detection of the underlying genetic defect. Today, it is generally accepted that the heterogeneity of mitochondrial disorders does not allow a standardized diagnostic procedure. Rather, the kind and the sequence of the diagnostic interventions have to be selected individually on the basis of the phe-notypic features presented by the patient. Particularly high quality demands have to be postulated for the biochemical analyses since they will often prejudice the diagnostics of mitochondriopathies: the validity of the analytic results should be confirmed by verified reference ranges, standardizations and experience for each kind of tissue used in the static and functional assays. The selection of the tissues used for biopsies and their storage is of central concern for high quality laboratory diagnostics. This talk will, therefore, focus on biopsy techniques, storage requirements of tissues for biochemical and structural investigations, sample transportation and preanalytical conditions representing the critical steps during the practical accomplishment. Today, it is generally accepted that a standardized diagnostic procedure is missing due the heterogeneity of the mitochondrial disorders.