Clinical, biochemical and genetic analyses in two Korean patients with medium-chain acyl-CoA dehydrogenase deficiency.
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive hereditary metabolic disorder of mitochondrial fatty acid β-oxidation. It is characterized by hypoketotic hypoglycemia, hyperammonemia, seizure, coma, and sudden infant death syndrome-like illness. The most frequently isolated mutation in the acyl-CoA dehydrogenase, medium-chain (ACADM) gene of Caucasian patients with MCADD is c.985A>G, but ethnic variations exist in the frequency of this mutation. Here, we describe 2 Korean pediatric cases of MCADD, which was detected during newborn screening by tandem mass spectrometry and confirmed by molecular analysis. The levels of medium-chain acylcarnitines, including octanoylcarnitine (C8), hexanoylcarnitine (C6), and decanoylcarnitine (C10), were typically elevated. Molecular studies revealed that Patient 1 was a compound heterozygote for c.449_452delCTGA (p.Thr150ArgfsX4) and c.461T>G (p.L154W) mutations, and Patient 2 was a compound heterozygote for c.449_452delCTGA (p.Thr150ArgfsX4) and c.1189T>A (p.Y397N) mutations. We detected asymptomatic patients with MCADD by using a newborn screening test and confirmed it by ACADM mutation analysis. This report presents evidence of the biochemical and molecular features of MCADD in Korean patients and, to the best of our knowledge, this is the first report of the c.461T>G mutation in the ACADM gene.
Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hye In
HI
Woo
Hyung-Doo
HD
Park
Yong-Wha
YW
Lee
Dong Hwan
DH
Lee
Chang-Seok
CS
Ki
Soo-Youn
SY
Lee
Jong-Won
JW
Kim
D042964:Acyl-CoA Dehydrogenase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D056910:Republic of Korea; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; C116917:acylcarnitine; D042964:Acyl-CoA Dehydrogenase; D002331:Carnitine
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