Oxygen consumption in platelets as an adjunct diagnostic method for pediatric mitochondrial disease

Background Diagnosing mitochondrial disease (MD) is a challenge. In addition to genetic analyses, clinical practice is to perform invasive procedures such as muscle biopsy for biochemical and histochemical analyses. Blood cell respirometry is rapid and noninvasive. Our aim was to explore its possible role in diagnosing MD. Methods Blood samples were collected from 113 pediatric patients, for whom MD was a differential diagnosis. A respiratory analysis model based on ratios (independent of mitochondrial specific content) was derived from a group of healthy controls and tested on the patients. The diagnostic accuracy of platelet respirometry was evaluated against routine diagnostic investigation. Results MD prevalence in the cohort was 16%. A ratio based on the respiratory response to adenosine diphosphate in the presence of complex I substrates had 96% specificity for disease and a positive likelihood ratio of 5.3. None of the individual ratios had sensitivity above 50%, but a combined model had 72% sensitivity. Conclusion Normal findings of platelet respirometry are not able to rule out MD, but pathological results make the diagnosis more likely and could strengthen the clinical decision to perform further invasive analyses. Our results encourage further study into the role of blood respirometry as an adjunct diagnostic tool for MD.