Diagnostic value of urine organic acids analysis among patients with primary mitochondrial disorders

Introduction. Primary mitochondrial disorders (PMD) are a group of clinically and genetically heterogeneous group of diseases characterized by a defective structure and functions of the Oxidative Phosphorylation System (OXPHOS). Despite the advantages of the next generation sequencing, diagnosis of PMD is still challenging. There is no currently available biomarker with high specificity and sensitivity. But the level of metabolites reflecting the defective OXPHOS is needed for making of a diagnosis of PMD. Aim: to reveal the level and spectrum of urine organic acids among patients with confirmed diagnosis (by molecular-genetic analysis) of PMD and to estimate the diagnostic value of the test. Methods. We measured 72 different metabolites in 84 urine samples from patients with PMD by GC-MS (7890А/5975С, Agilent Technologies, USA). Results. In 66/84 cases among the patients, we detected the abnormal level of urine organic acids. We observed a unique spectrum of metabolites in the patients with DGUOK-associated hepatopathy (abnormal levels of lactate, pyruvate, 3-hydroxybutyrate, and at the same time 4-hydroxyphenyllactate and 4-hydroxyphenylpyruvate). Using ROC-analysis one of the most informative biomarkers was 3-hydroxybutyrate. But due to the lack of specificity, it could not be classified as a valuable biomarker for PMD. The high level of pyruvate and 4-hydroxyphenyllactate could be taken into account to make a diagnosis of PMD

mitochondrial disorders, Leigh syndrome, mtDNA, urine organic acids, OXPHOS

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