Lab Med Online.  2011 Apr;1(2):115-119. 10.3343/lmo.2011.1.2.9.

Identification of a Novel Mutation in the MCCC2 Gene of a Korean Patient with 3-Methylcrotonyl-CoA Carboxylase Deficiency

• Kim BC
• Lee DH
• Ki CS
• Park HD
• Choi TY
• Shin JW
• Lee YW

• KMID: 1446279
• DOI: http://doi.org/10.3343/lmo.2011.1.2.9

Abstract

3-methylcrotonyl-CoA carboxylase deficiency is an autosomal recessive disorder characterized by a defect in leucine catabolism. We report the case of an 80-day-old patient with 3-methylcrotonyl-CoA carboxylase deficiency who had elevated levels of 3-hydroxyisovalerylcarnitine (45.56 micromol/L; reference range, <0.65 micromol/L), which was detected using tandem mass spectrometry during newborn screening, and elevated levels of 3-hydroxyisovaleric acid (375.75 mmol/mol Cr) and 3-methylcrotonylglycine (502.36 mmol/mol Cr ), which were detected in urine organic acid analysis. We performed direct sequence analysis of all the exons of the MCCC1 and MCCC2 genes. No mutations were detected in the direct sequence analysis of MCCC1. However sequencing of the MCCC2 gene revealed a mutation caused by a heterozygous G to C transversion [c.313G>C (p.Gly105Arg)] at nucleotide position 313 and a mutation caused by a heterozygous A to T transversion [c.1252A>T (p.lle418Phe)] at nucleotide position 1252. Identification of these 2 novel MCCC2 gene mutations in our patient suggested that analysis of the MCCC1 and MCCC2 genes might prove useful in the diagnosis of 3-methylcrotonyl-CoA carboxylase deficiency.

Keyword

3-Methylcrotonyl-CoA carboxylase; 3-Methylcrotonyl-CoA carboxylase deficiency; MCCC2 mutation

MeSH Terms

Carnitine
Exons
Glycine
Humans
Infant, Newborn
Leucine
Mass Screening
Reference Values
Sequence Analysis
Tandem Mass Spectrometry
Valerates
Carnitine
Glycine
Leucine
Valerates

Figure

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  Fig. 1 Urine organic acid analysis of an 80-day-old patient who had 3-methylcrotonyl-CoA carboxylase deficiency and elevated levels of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine.

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  Fig. 2 Mutation analysis of the MCCC2 gene in a Korean patient with 3-methylcrotonyl-CoA carboxylase deficiency. Direct sequencing of the MCCC2 gene shows overlapping peaks (arrow) at nucleotide position 313 because of a heterozygous G to C transversion [c.313G>C (p.Gly105Arg)] (A) and at nucleotide position 1252 because of a heterozygous A to T transversion [c.1252A>T (p.lle418Phe)] (B).

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