Neonatal screening for very long-chain acyl-coA dehydrogenase deficiency: enzymatic and molecular evaluation of neonates with elevated C14:1-carnitine levels.
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.
Liebig
Michaela
M
Department of General Pediatrics, University Children's Hospital, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
Schymik
Ina
I
Mueller
Martina
M
Wendel
Udo
U
Mayatepek
Ertan
E
Ruiter
Jos
J
Strauss
Arnold W
AW
Wanders
Ronald J A
RJ
Spiekerkoetter
Ute
U
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
D015415:Biomarkers; D005227:Fatty Acids; D010171:Palmitoyl Coenzyme A; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002331:Carnitine