Published online September 1, 2006
PEDIATRICS Vol. 118 No. 3 September 2006, pp. 1065-1069 (doi:10.1542/peds.2006-0666)
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ARTICLE

Neonatal Screening for Very Long-Chain Acyl-CoA Dehydrogenase Deficiency: Enzymatic and Molecular Evaluation of Neonates With Elevated C14:1-Carnitine Levels

Michaela Liebig, PhDa, Ina Schymika, Martina Muellera, Udo Wendel, MDa, Ertan Mayatepek, MDa, Jos Ruiterb, Arnold W. Strauss, MDc, Ronald J.A. Wanders, PhDb and Ute Spiekerkoetter, MDa

a Department of General Pediatrics, University Children's Hospital, Duesseldorf, Germany
b University of Amsterdam, Academic Medical Center, Departments of Pediatrics and Clinical Chemistry, Amsterdam, the Netherlands
c Department of Pediatrics and Vanderbilt Children's Hospital, Vanderbilt University, Nashville, Tennessee

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.

DESIGN. 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 µmol/L strongly suggests very long-chain acyl-coenzyme A dehydrogenase deficiency, whereas concentrations ≤1 µmol/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.

Key Words: tetradecenoylcarnitine • very long-chain acyl-CoA dehydrogenase • fatty acid oxidation • tandem mass spectrometry

Abbreviations: VLCADD—very long-chain acyl-coenzyme A dehydrogenase deficiency • MS/MS—tandem mass spectrometry • CoA—coenzyme A • MCADD—medium-chain acyl-coenzyme A dehydrogenase deficiency

Accepted May 3, 2006.


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