The metabolomics of organic acidemias: current advances and future prospects

Abstract

Organic acid disorders are an important entity of inborn errors of metabolism. They commonly present with an abrupt severe intoxication phenotype simulating sepsis, and if not promptly diagnosed and treated, they usually have irreversible neurological sequelae and may become fatal. New advances in metabolomic techniques, particularly mass spectrometric-based approaches, have aided in the development of a new way of thinking concerning diagnosing organic acidemias from identifying/quantifying one or two metabolites for each disorder to building a recognition pattern or a disease-based network of metabolites through both targeted and untargeted metabolomics. In this review, we will summarize the evolution of diagnostic approaches for organic acidemias and their broad phenotypic spectrum. We will further discuss the interplay between organic acidemias and mitochondrial dysfunction and will try to present the concepts behind the various metabolomics techniques and their applications for the diagnosis and management of organic acidemias.