Kalıtsal Metabolik Hastalıklarda Yeni Nesil Omiks Profilleme Uygulamaları

Abstract

This study aimed to characterize disease-specific biomarkers and metabolic alterations by comparing the metabolomic and lipidomic profiles of patients with phenylketonuria (PKU), mild hyperphenylalaninemia (HFA), tetrahydrobiopterin (BH4)-responsive HFA, biotinidase deficiency, and hyperlipidemia—diagnosed through established clinical and routine biochemical analyses—together with one patient carrying a pathogenic VARS2 mutation identified by whole-exome sequencing, and one undiagnosed patient, against healthy controls. Distinct metabolites showing significant alterations compared to healthy individuals were identified in each phenotype, and these metabolites demonstrated potential biomarker properties. Moreover, pronounced disease-specific metabolic pathway alterations were observed in all patient groups, alongside a set of commonly affected fundamental biological processes. In PKU patients, differential metabolic fingerprints were detected depending on the clinical classification and metabolic control status, leading to the identification of novel candidate biomarkers for monitoring metabolic control. In biotinidase deficiency, the observed lipid imbalances were found to potentially disrupt cellular energy production and signaling pathways, underscoring the importance of biotin supplementation and dietary regulation. Additionally, the metabolic differences identified in the individual harboring a VARS2 gene mutation contributed to a better molecular understanding of the disease and provided valuable insights for the development of targeted therapies. In conclusion, this study highlights the significant potential of metabolomic and lipidomic profiling in phenotypic stratification, elucidation of disease mechanisms, and the discovery of novel disease-specific biomarkers.