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 journalArticle

51 Citations (Scopus)

Abstract

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
Volume78
Issue number4
DOIs
StatePublished - Apr 1 2003

Fingerprint

Butyryl-CoA Dehydrogenase
Blood
Genes
Newborn Infant
African Americans
Population
Mutation
Disease Susceptibility
Hispanic Americans
Gene Frequency
Exons
Alleles
Genotype
Phenotype
acylcarnitine
Proteins
Short chain Acyl CoA dehydrogenase deficiency

Keywords

  • ACADS
  • 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

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

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

In: Molecular Genetics and Metabolism, Vol. 78, No. 4, 01.04.2003, p. 239-246.

Research output: Contribution to journalArticle

Nagan, Narasimhan ; Kruckeberg, Kent E. ; Tauscher, Angela L. ; Bailey, Karen Snow ; Rinaldo, Piero ; Matern, Dietrich. / 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. In: Molecular Genetics and Metabolism. 2003 ; Vol. 78, No. 4. pp. 239-246.
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AB - 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.

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KW - Tandem mass spectrometry

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