title: Biochemical and molecular characteristics of patients with organic acidaemias and urea cycle disorders identified through newborn screening.
abstract: BACKGROUND
  In recent years it has become clear that newborn screening (NBS) programmes using tandem mass spectrometry identify "patients" with "classical" inborn errors of metabolism who are asymptomatic. This observation raises issues regarding medicalization of "non-diseases," potentially unnecessary treatment and unnecessary anxiety to parents.
  
  
  OBJECTIVE
  This study aims to identify possible markers that may assist in predicting the need for treatment of infants with "classical" organic acidaemias (OA) and urea cycle disorders (UCD) diagnosed through NBS.
  
  
  METHODS
  Medical records of all patients with classical OA and UCD detected through the Victorian NBS programme from February 2002 to January 2014, or diagnosed clinically between 1990 and January 2002 were retrospectively reviewed.
  
  
  RESULTS
  Neonatal presentation did not always predict the need for on-going strict treatment. Blood concentrations of amino acids and acyl-carnitines and the changes thereof in follow-up samples correlated with severity in citrullinaemia-I, possibly isovaleric acidaemia but not in argininosuccinic aciduria or propionic acidaemia. Some specific mutations correlate with "attenuated" citrullinaemia-I. Gender may affect clinical outcome in propionic acidaemia.
  
  
  CONCLUSIONS
  Changes in blood concentration of certain metabolites (amino acids, acyl-carnitines) in the first weeks of life may be predictive of the need for treatment in some disorders but not in others. Mutation analysis may be predictive in some disorders but whether or not this should be considered as second-tier testing in NBS should be discussed separately.
authors.affiliation: Metabolic Research, Murdoch Childrens Research Institute, and Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Australia; Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Barends
authors.affiliation: Metabolic Research, Murdoch Childrens Research Institute, and Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Pitt
authors.affiliation: Metabolic Research, Murdoch Childrens Research Institute, and Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Morrissy
authors.affiliation: Metabolic Research, Murdoch Childrens Research Institute, and Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Tzanakos
authors.affiliation: Metabolic Research, Murdoch Childrens Research Institute, and Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Boneh
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods; D012189:Retrospective Studies; D056806:Urea Cycle Disorders, Inborn / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy
chemical_list: D015415:Biomarkers
keywords: Newborn screening; Organic acidaemia; Tandem mass spectrometry; Urea cycle disorder