The frequency of short-chain acyl-CoA dehydrogenase gene variants in the US population and correlation with the C4-acylcarnitine concentration in newborn blood spots

Narasimhan Nagan, Kent E. Kruckeberg, Angela L. Tauscher, Karen Snow Bailey, Piero Rinaldo, Dietrich Matern

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a clinically heterogeneous disorder. The clinical phenotype varies from fatal metabolic decompensation in early life to subtle adult onset, some patients remain asymptomatic. Two mutations (511C>T; 625G>A) have been described in exons 5 and 6 of the SCAD gene. Although they alter the structural and catalytic properties of the SCAD protein, these variants are not true disease-causing mutations but confer disease susceptibility. Previous studies found these gene variants to be common in Europeans. We aimed to establish the frequency of these variants in the US population and to determine whether the presence of these variants correlates with elevated butyrylcarnitine (C4-acylcarnitine) concentrations in newborn blood spots. Based on the analysis of 694 samples, we found that the allele frequency of the 625G>A variant was significantly higher (22%) than that of the 511C>T variant (3%). These gene variants were detected in either homozygous or compound heterozygous form in 7% of the study population. Additionally, the frequency of the 625G>A allele in the Hispanic population (30%) was significantly higher than that of the African-American (9%) and Asian (13%) subpopulations. A previously unreported variant, IVS 5 (-10) C>T, was identified in three African-American newborns (0.3%). The C4-acylcarnitine concentration in blood spots was significantly higher in subjects homozygous for the 625A variant when compared to those homozygous for the wild type (p<0.0001). However, none of the observed genotypes was associated with a concentration of C4-acylcarnitine that would be consistent with a biochemical diagnosis of SCAD deficiency.

Original languageEnglish (US)
Pages (from-to)239-246
Number of pages8
JournalMolecular genetics and metabolism
Issue number4
StatePublished - Apr 1 2003


  • Acylcarnitine analysis
  • Butyrylcarnitine
  • Fatty acid β-oxidation
  • Melting curve analysis
  • Newborn screening
  • Short-chain acyl-CoA dehydrogenase deficiency
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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