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

Abstract

BackgroundDiagnosing 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.MethodsBlood 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.ResultsMD 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.ConclusionNormal 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.

Correlation of mitochondrial respiration in platelets, peripheral blood mononuclear cells and muscle fibers

“…In total, 318 individuals were included. Data from either PBMCs or plalelets, or both, for these individuals (but not the data from the 24 muscle biopsies) have been published before in other contexts [ [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] ]. The ages ranged from 3 days to 86 years with a roughly equal sex distribution (148 females).…”

“…There were 82 children (under the age of 18 years) in this study. Out of these, 23 were otherwise healthy patients undergoing minor elective surgery [ 13 ]. There were 59 pediatric patients, nine of whom had confirmed primary mitochondrial disease.…”

“…Platelets and PBMCs from nine pediatric patients with mitochondrial disease were compared to samples from another group of pediatric patients where mitochondrial disease was initially included in the differential diagnosis. (The patients in this analysis are a subset of the patients presented in a previous publication [ 13 ]. The subset comprises all cases where both platelet and PBMC data were available.…”

“…The subset comprises all cases where both platelet and PBMC data were available. For more information on the individual mitochondrial diagnoses we refer to Table 3 of that publication; the patients included in this study are the cases indexed as 2, 3, 5, 6, 10, 11, 13, 14 and 15 [ 13 ].) Several of the respiratory ratios were significantly altered in the group with mitochondrial disease, mainly in platelets ( Fig.…”

“…Since our analysis showed that internal ratios increased the correlation as well as, or better than CS normalization, we only examined the ratios. (This method of normalization was also used in our previous related work on patients with mitochondrial disease [ 13 ].) On a group level, the comparisons showed significant differences in several ratios.…”