Dataset Information

Comprehensive metabolomic/lipidomic characterization of patients with mitochondrial ATP synthase, short-chain acyl-CoA dehydrogenase and combined variant deficiencies

ABSTRACT: Objective: This study aims to characterize the metabolic alterations in patients with inherited mitochondrial enzymopathies. We focused on targeted metabolomic, organic acid and lipidomic analyses of patients with TMEM70 deficiency (TMEM70d), short-chain acyl-CoA dehydrogenase deficiency (SCADd), and individuals with both deficiencies (TMEM70d-SCADd). Methods: Serum and urine samples were collected from patients with TMEM70d (n=13), SCADd (n=11), TMEM70d-SCADd (n=3), and controls (n=38). Analyses were conducted using high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Univariate and multivariate statistical evaluation was performed to identify significant metabolic differences between patient groups and controls. Results: Distinct metabolic profiles were observed in urine and serum samples of patients with TMEM70d, SCADd, and TMEM70d-SCADd compared to controls. Urinary metabolomics revealed significant elevations in butyrylcarnitine and metabolites related to branched-chain amino acid degradation in SCADd and TMEM70d-SCADd patients. Serum metabolomic analysis indicated alterations in pyruvate metabolism, citric acid cycle intermediates, and acylcarnitine metabolism in TMEM70d and TMEM70d-SCADd patients. Lipidomic analysis showed decreased levels of glycerophospholipids and sphingolipids across all patient groups. Conclusion: Patients with TMEM70d, SCADd, and TMEM70d-SCADd exhibit distinct metabolic signatures characterized by disturbances in energy metabolism, amino acid degradation, and lipid homeostasis. The combination of TMEM70d and SCADd leads to synergistic metabolic effects, emphasizing the importance of comprehensive metabolic profiling in understanding complex mitochondrial disorders and identifying potential biomarkers for diagnosis and treatment monitoring.

INSTRUMENT(S): ExionLC, QTRAP 6500+

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: David Friedecky