title: Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias.
abstract: BACKGROUND
  3-Hydroxypalmitoleoyl-carnitine (C16:1-OH) has recently been reported to be elevated in acylcarnitine profiles of patients with propionic acidemia (PA) or methylmalonic acidemia (MMA) during expanded newborn screening (NBS). High levels of C16:1-OH, combined with other hydroxylated long chain acylcarnitines are related to long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and trifunctional protein (TFP) deficiency.
  
  
  METHODS
  The acylcarnitine profile of two LCHADD patients was evaluated using liquid chromatography-tandem mass spectrometric method. A specific retention time was determined for each hydroxylated long chain acylcarnitine. The same method was applied to some neonatal dried blood spots (DBSs) from PA and MMA patients presenting abnormal C16:1-OH concentrations.
  
  
  RESULTS
  The retention time of the peak corresponding to C16:1-OH in LCHADD patients differed from those in MMA and PA patients. Heptadecanoylcarnitine (C17) has been identified as the novel biomarker specific for PA and MMA patients through high resolution mass spectrometry (Orbitrap) experiments. We found that 21 out of 23 neonates (22 MMA, and 1PA) diagnosed through the Tuscany region NBS program exhibited significantly higher levels of C17 compared to controls. Twenty-three maternal deficiency (21 vitamin B12 deficiency, 1 homocystinuria and 1 gastrin deficiency) samples and 82 false positive for elevated propionylcarnitine (C3) were also analyzed.
  
  
  CONCLUSIONS
  We have characterized a novel biomarker able to detect propionate disorders during expanded newborn screening (NBS). The use of this new biomarker may improve the analytical performances of NBS programs especially in laboratories where second tier tests are not performed.
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratory, Pediatric Neurology Unit and Laboratories, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.affiliation: Newborn Screening and Molecular Biology Branch, Centers for Disease Control and Prevention, Atlanta, GA USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haynes
authors.affiliation: Department of Statistics, Computer Science and Applications 'G. Parenti' University of Florence, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Grisotto
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratory, Pediatric Neurology Unit and Laboratories, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ombrone
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratory, Pediatric Neurology Unit and Laboratories, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Funghini
authors.affiliation: Analytics and Early Formulations Department, Chiesi Farmaceutici S.P.A., Parma, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Moretti
authors.affiliation: Research, Innovation and International Relations Office, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: McGreevy
authors.affiliation: Department of Statistics, Computer Science and Applications 'G. Parenti' University of Florence, Florence, Italy.
authors.forename: Annibale
authors.initials: A
authors.lastname: Biggeri
authors.affiliation: Pediatric Neurology Unit and Laboratories, Meyer Children's University Hospital, Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Newborn Screening and Clinical Laboratory, Málaga Regional Hospital, Málaga, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Yahyaoui
authors.affiliation: Department of Pathology and laboratory Medicine, Children's Mercy Hospital, Kansas City, MO, USA.
authors.forename: Uttam
authors.initials: U
authors.lastname: Garg
authors.affiliation: Newborn Screening Section, Michigan Department of Community Health, Bureau of Laboratories, Chemistry and Toxicology, Lansing, MI, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Seeterlin
authors.affiliation: The Pediatrix Center for Research, Education and Quality Pediatrix Medical Group, Concord Terrace Sunrise, FL, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Chace
authors.affiliation: Newborn Screening and Molecular Biology Branch, Centers for Disease Control and Prevention, Atlanta, GA USA.
authors.forename: Victor R
authors.initials: VR
authors.lastname: De Jesus
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratory, Pediatric Neurology Unit and Laboratories, Meyer Children's University Hospital, Florence, Italy. Electronic address: g.lamarca@meyer.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood* / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening; D056693:Propionic Acidemia / Q000097:blood* / Q000175:diagnosis*; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; C000607153:heptadecanoylcarnitine; D002331:Carnitine
keywords: Acylcarnitine; Expanded newborn screening; Heptadecanoylcarnitine; Methylmalonic acidemia; Propionic acidemia; Propionylcarnitine