Mitochondrial respiratory chain disease discrimination by retrospective cohort analysis of blood metabolites.

[pyruvate dehydrogenase deficiency]

Diagnosing primary mitochondrial respiratory chain (RC ) dysfunction has long relied on invasive tissue biopsies , since no blood -based biomarker has been shown to have sufficiently high sensitivity and specificity across the myriad of individual clinical presentations . We sought to determine whether cohort-level evaluation of commonly obtained blood analytes might reveal consistent patterns to discriminate a heterogenous group of primary mitochondrial RC disease subjects both from control individuals and from subjects with pyruvate dehydrogenase deficiency .F ollowing IRB approval , 62 biochemical analyte concentrations or ratios were retrospectively analyzed in three well-defined and intentionally heterogeneous subject cohorts reflective of clinical practice : [1 ] Primary mitochondrial disease (n =19 ); [2 ] pyruvate dehydrogenase deficiency (n =4 ); and [3 ] controls (n =27 ). Blood analyte categories included comprehensive chemistry profile , creatine kinase , lipoprotein profile , lactate , pyruvate , and plasma amino acid profile . Non-parametric analyses were used to compare the median of each analyte level between cohorts .Disease cohorts differed significantly in their median levels of triglycerides , lactate , pyruvate , and multiple individual plasma amino acids . Primary mitochondrial disease was significantly discriminated at the cohort level from pyruvate dehydrogenase deficiency by greater pyruvate and alanine elevation in pyruvate dehydrogenase deficiency , as well as significantly increased branched chain amino acid (BCAA ) levels and increased ratios of individual BCAAs to glutamate in mitochondrial disease . In addition , significant elevation of median blood triglyceride level was seen in the primary mitochondrial disease cohort .Blood metabolite profile analysis can discriminate a heterogeneous cohort of primary mitochondrial disease both from controls and from pyruvate dehydrogenase deficiency . Elevated BCAA levels , either absolutely or when considered relative to the level of glutamate , are common metabolic sequelae of primary mitochondrial RC disease . Prospective study is needed to validate observed plasma metabolite alterations as a potential biomarker of disease both in larger cohorts and at the individual subject level .

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Diseases presenting "blood analytes" symptom

pyruvate dehydrogenase deficiency

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