title: Neonatal screening for very long-chain acyl-coA dehydrogenase deficiency: enzymatic and molecular evaluation of neonates with elevated C14:1-carnitine levels.
abstract: OBJECTIVE
  Neonatal screening programs for very long-chain acyl-coenzyme A dehydrogenase deficiency have been implemented recently in various countries. Mildly elevated C14:1-carnitine on day 3 of life strongly suggests very long-chain acyl-coenzyme A dehydrogenase deficiency.
  
  
  METHODS
  We characterized 11 neonates with elevated C14:1-carnitine by enzyme and molecular analyses. Palmitoyl-coenzyme A oxidation was measured in lymphocytes. Sequencing of all 20 exons of the VLCAD gene was performed from genomic DNA.
  
  
  RESULTS
  Palmitoyl-coenzyme A oxidation revealed significantly decreased residual activities consistent with very long-chain acyl-coenzyme A dehydrogenase deficiency in 7 neonates. In 2 individuals, residual activities of 48% and 44%, respectively, suggested heterozygosity. Two disease-causing mutations were detected in 6 of 7 neonates with very long-chain acyl-coenzyme A dehydrogenase deficiency; in the remaining 1 patient, only 1 mutation was identified. Of 2 individuals with residual activities consistent with heterozygosity, 1 was heterozygous for a VLCAD mutation. The other child and both individuals with normal palmitoyl-coenzyme A oxidation had normal genotypes.
  
  
  CONCLUSIONS
  In 4 of 11 neonates identified with elevated C14:1-carnitine, very long-chain acyl-coenzyme A dehydrogenase deficiency was excluded. A C14:1-carnitine level > 1 micromol/L strongly suggests very long-chain acyl-coenzyme A dehydrogenase deficiency, whereas concentrations < or = 1 micromol/L do not allow a clear discrimination among affected patients, carriers, and healthy individuals. Further diagnostic evaluation, including enzyme and molecular analyses, is essential to identify very long-chain acyl-coenzyme A dehydrogenase deficiency correctly.
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Liebig
authors.forename: Ina
authors.initials: I
authors.lastname: Schymik
authors.forename: Martina
authors.initials: M
authors.lastname: Mueller
authors.forename: Udo
authors.initials: U
authors.lastname: Wendel
authors.forename: Ertan
authors.initials: E
authors.lastname: Mayatepek
authors.forename: Jos
authors.initials: J
authors.lastname: Ruiter
authors.forename: Arnold W
authors.initials: AW
authors.lastname: Strauss
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Ute
authors.initials: U
authors.lastname: Spiekerkoetter
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency* / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis; D002331:Carnitine / Q000031:analogs & derivatives / Q000032:analysis; D015331:Cohort Studies; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis*; D008214:Lymphocytes / Q000201:enzymology; D015997:Neonatal Screening; D010084:Oxidation-Reduction; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D017422:Sequence Analysis, DNA; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D010171:Palmitoyl Coenzyme A; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002331:Carnitine