Biochemical therapy monitoring with subcutaneous microdialysis in mitochondrial encephalomyopathies

Although a great progress has been made in the understanding of the molecular bases of mitochondrial disorders, therapy is problematic. Based on theoretical implications and in vitro experiments the treatment involves the administration of vitamins, cofactors, and modification of the nutrition, eg. Ketogenic diet in pyruvate dehydrogenase deficiency (PDH). The evaluation of the efficacy of therapeutical approaches is difficult in regard to the large variability of the clinical course.

Subcutaneous microdialysis (sc MD) permits the adaptation of the treatment by detection of metabolic effects on tissue metabolism caused by modifying the therapy.

Microdialysis is a continuous sampling method to analyse a patients extracellular tissue chemistry for several days and weeks without draining blood.

Based on our experience with 42 patients, the theoretical basis, method and domains of applying biochemical monitoring with sc MD shall be demonstrated. We report our minimally traumatic insertion technique for microdialysis catheters developed for pediatric patients applicable even in extremely low birth weight infants.

Repeated measurement of metabolites (eg. Lactate, pyruvate, carnitines, amino acids, glucose, glycerol) using sc MD is without impairement of the patient, even during sleep, and results in diurnal profiles of the metabolites. The great amount of values under standardized conditions allows the statistical evaluation of the therapeutic effects on tissue metabolism as part of the therapeutic evaluation and basis for individual modification of the treatment.

This is demonstrated for mitochondrial diseases, pyruvate dehydrogenase deficiency and complex I deficiency of the respiratory chain, both treated with ketogenic diet.