title: Targeted metabolomics in the expanded newborn screening for inborn errors of metabolism.
abstract: Inborn errors of metabolism are genetic disorders due to impaired activity of enzymes, transporters, or cofactors resulting in accumulation of abnormal metabolites proximal to the metabolic block, lack of essential products or accumulation of by-products. Many of these disorders have serious clinical consequences for affected neonates, and an early diagnosis allows presymptomatic treatment which can prevent severe permanent sequelae and in some cases death. Expanded newborn screening for these diseases is a promising field of targeted metabolomics. Here we report the application, between 2007 and 2014, of this approach to the identification of newborns in southern Italy at risk of developing a potentially fatal disease. The analysis of amino acids and acylcarnitines in dried blood spots by tandem mass spectrometry revealed 24 affected newborns among 45,466 infants evaluated between 48 and 72 hours of life (overall incidence: 1 : 1894). Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Five infants were diagnosed with medium-chain acyl CoA dehydrogenase deficiency, 1 with methylmalonic acidemia with homocystinuria type CblC, 2 with isolated methylmalonic acidemia, 1 with propionic acidemia, 1 with isovaleric academia, 1 with isobutyryl-CoA dehydrogenase deficiency, 1 with beta ketothiolase deficiency, 1 with short branched chain amino acid deficiency, 1 with 3-methlycrotonyl-CoA carboxylase deficiency, 1 with formimino-transferase cyclodeaminase deficiency, and 1 with cystathionine-beta-synthase deficiency. Seven cases of maternal vitamin B12 deficiency and 1 case of maternal carnitine uptake deficiency were detected. This study supports the widespread application of metabolomic-based newborn screening for these genetic diseases.
authors.affiliation: CEINGE-Biotecnologie Avanzate scarl, Napoli, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scolamiero
authors.forename: Carla
authors.initials: C
authors.lastname: Cozzolino
authors.forename: Lucia
authors.initials: L
authors.lastname: Albano
authors.forename: Antonella
authors.initials: A
authors.lastname: Ansalone
authors.forename: Marianna
authors.initials: M
authors.lastname: Caterino
authors.forename: Graziella
authors.initials: G
authors.lastname: Corbo
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: di Girolamo
authors.forename: Cristina
authors.initials: C
authors.lastname: Di Stefano
authors.forename: Adriano
authors.initials: A
authors.lastname: Durante
authors.forename: Giovanni
authors.initials: G
authors.lastname: Franzese
authors.forename: Ignazio
authors.initials: I
authors.lastname: Franzese
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gallo
authors.forename: Paolo
authors.initials: P
authors.lastname: Giliberti
authors.forename: Laura
authors.initials: L
authors.lastname: Ingenito
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ippolito
authors.forename: Basilio
authors.initials: B
authors.lastname: Malamisura
authors.forename: Pietro
authors.initials: P
authors.lastname: Mazzeo
authors.forename: Antonella
authors.initials: A
authors.lastname: Norma
authors.forename: Daniela
authors.initials: D
authors.lastname: Ombrone
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Parenti
authors.forename: Silvana
authors.initials: S
authors.lastname: Pellecchia
authors.forename: Rita
authors.initials: R
authors.lastname: Pecce
authors.forename: Ippolito
authors.initials: I
authors.lastname: Pierucci
authors.forename: Roberta
authors.initials: R
authors.lastname: Romanelli
authors.forename: Anna
authors.initials: A
authors.lastname: Rossi
authors.forename: Massimo
authors.initials: M
authors.lastname: Siano
authors.forename: Teodoro
authors.initials: T
authors.lastname: Stoduto
authors.forename: Guglielmo R D
authors.initials: GR
authors.lastname: Villani
authors.forename: Generoso
authors.initials: G
authors.lastname: Andria
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.forename: Giulia
authors.initials: G
authors.lastname: Frisso
authors.forename: Margherita
authors.initials: M
authors.lastname: Ruoppolo
mesh_terms: D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis*; D055432:Metabolomics / Q000379:methods*; D015997:Neonatal Screening / Q000379:methods*
chemical_list: D015415:Biomarkers