title: Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening.
abstract: OBJECTIVE
  Our goal was to describe the clinical spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by routine newborn screening and assess factors associated with elevations of octanoylcarnitine in newborns and characteristics associated with adverse clinical consequences of medium-chain acyl-CoA dehydrogenase deficiency.
  
  
  METHODS
  The first 47 medium-chain acyl-CoA dehydrogenase deficiency cases detected by the New England Newborn Screening Program were classified according to initial and follow-up octanoylcarnitine values, octanoylcarnitine-decanoylcarnitine ratios, medium-chain acyl-CoA dehydrogenase genotype, follow-up biochemical parameters, and feeding by breast milk or formula.
  
  
  RESULTS
  All 20 patients who were homozygous for 985A-->G had high initial octanoylcarnitine values (7.0-36.8 microM) and octanoylcarnitine-decanoylcarnitine ratios (7.0-14.5), whereas the 27 patients with 0 to 1 copy of 985A-->G exhibited a wide range of octanoylcarnitine values (0.5-28.6 microM) and octanoylcarnitine-decanoylcarnitine ratios (0.8-12.7). Initial newborn octanoylcarnitine values decreased by days 5 to 8, but the octanoylcarnitine-decanoylcarnitine ratio generally remained stable. Among 985A-->G homozygotes, breastfed newborns had higher initial octanoylcarnitine values than newborns who received formula. Adverse events occurred in 5 children, 4 985A-->G homozygotes and 1 compound heterozygote with a very high initial octanoylcarnitine: 2 survived severe neonatal hypoglycemia, 1 survived a severe hypoglycemic episode at 15 months of age, and 2 died as a result of medium-chain acyl-CoA dehydrogenase deficiency at ages 11 and 33 months.
  
  
  CONCLUSIONS
  Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency has detected cases with a wide range of genotypes and biochemical abnormalities. Although most children do well, adverse outcomes have not been entirely avoided. Assessment of potential risk and determination of appropriate treatment remain a challenge.
authors.affiliation: New England Newborn Screening Program, University of Massachusetts Medical School, 305 South St, Jamaica Plain, MA 02130, USA. ho-wen.hsu@umassmed.edu
authors.forename: Ho-Wen
authors.initials: HW
authors.lastname: Hsu
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Zytkovicz
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Comeau
authors.forename: Arnold W
authors.initials: AW
authors.lastname: Strauss
authors.forename: Deborah
authors.initials: D
authors.lastname: Marsden
authors.forename: Vivian E
authors.initials: VE
authors.lastname: Shih
authors.forename: George F
authors.initials: GF
authors.lastname: Grady
authors.forename: Roger B
authors.initials: RB
authors.lastname: Eaton
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001942:Breast Feeding; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D041943:Infant Formula; D007231:Infant, Newborn; D015997:Neonatal Screening; D017354:Point Mutation; D017422:Sequence Analysis, DNA
chemical_list: D015415:Biomarkers; C002893:decanoylcarnitine; D042964:Acyl-CoA Dehydrogenase; C008698:octanoylcarnitine; D002331:Carnitine