The frequency of short-chain acyl-CoA dehydrogenase gene variants in the US population and correlation with the C(4)-acylcarnitine concentration in newborn blood spots.
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 (C(4)-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 C(4)-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 C(4)-acylcarnitine that would be consistent with a biochemical diagnosis of SCAD deficiency.
Nagan
Narasimhan
N
Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Kruckeberg
Kent E
KE
Tauscher
Angela L
AL
Bailey
Karen Snow
KS
Rinaldo
Piero
P
Matern
Dietrich
D
D000483:Alleles; D044926:Butyryl-CoA Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D005091:Exons; D005227:Fatty Acids / Q000378:metabolism; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008403:Mass Screening; D013058:Mass Spectrometry; D009154:Mutation; D010641:Phenotype; D012542:Scattering, Radiation; D013696:Temperature; D014481:United States
D005227:Fatty Acids; C116917:acylcarnitine; C427065:butyrylcarnitine; D044926:Butyryl-CoA Dehydrogenase; D002331:Carnitine