Korean J Lab Med.  2011 Jan;31(1):54-60. 10.3343/kjlm.2011.31.1.54.

Clinical, Biochemical and Genetic Analyses in Two Korean Patients with Medium-chain Acyl-CoA Dehydrogenase Deficiency

Affiliations
  • 1Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 2Department of Laboratory Medicine & Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea. nayadoo@hanmail.net lywmd@hanmail.net
  • 3Department of Pediatrics, College of Medicine, Soonchunhyang University, Seoul, Korea.

Abstract

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive hereditary metabolic disorder of mitochondrial fatty acid beta-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.

Keyword

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD); ACADM; Novel mutation

MeSH Terms

Acyl-CoA Dehydrogenase/chemistry/deficiency/genetics
Asian Continental Ancestry Group/*genetics
Base Sequence
Biological Markers/blood
Carnitine/analogs & derivatives/blood
DNA Mutational Analysis
Exons
Female
Gene Deletion
Heterozygote
Humans
Infant, Newborn
Lipid Metabolism, Inborn Errors/diagnosis/genetics
Male
Mutation
Neonatal Screening
Republic of Korea
Tandem Mass Spectrometry

Figure

  • Fig. 1 ACADM mutations detected by sequence analysis. Compound heterozygote consisting of a known mutation and a novel mutation in Patient 1. The known maternally-derived allele was a 4-bp deletion at position 449 to 452 in exon 6, altering codon 153 from a proline to a termination codon (p.Thr150ArgfsX4). The novel mutant allele originated from the patient's father and was a T to G transition at position 461 in exon 6, resulting in a leucine to tryptophan change at codon 154 (p.L154W).

  • Fig. 2 Diagram of protein structure near the c.461T>G (p.L154W) mutation. (A) Leu154 lies on the loop between the N-terminal α domain and β domain, shown in sky blue. (B) The novel Leu154Trp mutation produces side-chain clash with Glu152 (dotted pink line). Hydrogen bonds are shown by the dotted green lines.


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Sung Eun Cho, Eun Jung Park, Dong Hee Seo, In Bum Lee, Hyun Ju Lee, Dae-Yeon Cho, Jung Min Oh
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