title: Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias.
abstract: Organic acidemias (OAs) are inherited metabolic disorders caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders result in the accumulation of mono-, di-, or tricarboxylic acids, generally referred to as organic acids. The OA outcomes can involve different organs and/or systems. Some OA disorders are easily managed if promptly diagnosed and treated, whereas, in others cases, such as propionate metabolism-related OAs (propionic acidemia, PA; methylmalonic acidemia, MMA), neither diet, vitamin therapy, nor liver transplantation appears to prevent multiorgan impairment. Here, we review the recent developments in dissecting molecular bases of OAs by using integration of mass spectrometry- (MS-) based metabolomic and proteomic strategies. MS-based techniques have facilitated the rapid and economical evaluation of a broad spectrum of metabolites in various body fluids, also collected in small samples, like dried blood spots. This approach has enabled the timely diagnosis of OAs, thereby facilitating early therapeutic intervention. Besides providing an overview of MS-based approaches most frequently used to study the molecular mechanisms underlying OA pathophysiology, we discuss the principal challenges of metabolomic and proteomic applications to OAs.
authors.affiliation: IRCCS SDN, 80143 Naples, Italy.
authors.forename: Esther
authors.initials: E
authors.lastname: Imperlini
authors.affiliation: CEINGE Biotecnologie Avanzate s.c.a.r.l., 80145 Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Santorelli
authors.affiliation: IRCCS SDN, 80143 Naples, Italy; Dipartimento di Scienze Motorie e del Benessere, Università di Napoli "Parthenope", 80133 Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Orrù
authors.affiliation: CEINGE Biotecnologie Avanzate s.c.a.r.l., 80145 Naples, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scolamiero
authors.affiliation: CEINGE Biotecnologie Avanzate s.c.a.r.l., 80145 Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", 80121 Naples, Italy; Associazione Culturale DiSciMuS RCF, Casoria, 80026 Naples, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Ruoppolo
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", 80121 Naples, Italy.
authors.forename: Marianna
authors.identifier: 0000-0001-6035-8213
authors.initials: M
authors.lastname: Caterino
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers