title: Newborn screening for medium chain acyl-CoA dehydrogenase deficiency in England: prevalence, predictive value and test validity based on 1.5 million screened babies.
abstract: BACKGROUND
  Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare, life-threatening condition. Early diagnosis by screening asymptomatic newborns may improve outcome, but the benefit to newborns identified with variants not encountered clinically is uncertain.
  
  
  OBJECTIVE
  To estimate, overall and by ethnic group: screen-positive prevalence and predictive value (PPV); MCADD prevalence; proportion MCADD variants detected of predicted definite or uncertain clinical importance.
  
  
  METHODS
  All births in areas of high ethnic minority prevalence in England.
  
  
  METHODS
  Prospective multicentre pilot screening service; testing at age five to eight days; standardized screening, diagnostic and management protocols; independent expert review of screen-positive cases to assign MCADD diagnosis and predicted clinical importance (definite or uncertain).
  
  
  RESULTS
  Approximately 1.5 million babies (79% white; 10% Asian) were screened. MCADD was confirmed in 147 of 190 babies with a positive screening result (screen-positive prevalence: 1.20 per 10,000; MCADD prevalence: 0.94 per 10,000; PPV 77% [95% CI 71-83]), comprising 103 (70%) with MCADD variants of definite clinical importance (95 white [95%]; 2 Asian [2%]) and 44 (30%) with variants of uncertain clinical importance (29 white [67%]; 12 Asian [28%]).
  
  
  CONCLUSIONS
  One baby in every 10,000 born in England is diagnosed with MCADD by newborn screening; around 60 babies each year. While the majority of MCADD variants detected are predicted to be of definite clinical importance, this varies according to ethnic group, with variants of uncertain importance most commonly found in Asian babies. These findings provide support for MCADD screening but highlight the need to take account of the ethnic diversity of the population tested at implementation.
authors.affiliation: MRC Centre of Epidemiology for Child Health, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, United Kingdom.
authors.forename: Juliet
authors.initials: J
authors.lastname: Oerton
authors.forename: Javaria M
authors.initials: JM
authors.lastname: Khalid
authors.forename: Guy
authors.initials: G
authors.lastname: Besley
authors.forename: R Neil
authors.initials: RN
authors.lastname: Dalton
authors.forename: Melanie
authors.initials: M
authors.lastname: Downing
authors.forename: Anne
authors.initials: A
authors.lastname: Green
authors.forename: Mick
authors.initials: M
authors.lastname: Henderson
authors.forename: Steve
authors.initials: S
authors.lastname: Krywawych
authors.forename: James
authors.initials: J
authors.lastname: Leonard
authors.forename: Brage S
authors.initials: BS
authors.lastname: Andresen
authors.forename: Carol
authors.initials: C
authors.lastname: Dezateux
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D003663:Decision Trees; D004739:England / Q000453:epidemiology; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D008297:Male; D015997:Neonatal Screening / Q000941:ethics / Q000379:methods* / Q000592:standards; D010865:Pilot Projects; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D015203:Reproducibility of Results; D044465:White People / Q000235:genetics
chemical_list: D042964:Acyl-CoA Dehydrogenase