Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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Identification of a novel frameshift mutation (L345Sfs*15) in a Korean neonate with methylmalonic acidemia

  • Kim, Young A (Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine) ;
  • Kim, Ji-Yong (Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine) ;
  • Kim, Yoo-Mi (Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine) ;
  • Cheon, Chong Kun (Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine)
  • Received : 2017.10.31
  • Accepted : 2017.12.02
  • Published : 2017.12.31
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Abstract

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder characterized by an abnormal accumulation of methylmalonyl-CoA and methylmalonate in body fluids without hyperhomocysteinemia. Cardiac disease is a rarely known lethal complication of MMA, herein, we report a Korean neonate diagnosed with MMA on the basis of biochemical and genetic findings, who developed cardiomyopathy, resulting in sudden death. The patient presented vomiting and lethargy at 3 days of age. Initially, the patient had an increased plasma propionylcarnitine/acetylcarnitine concentration ratio of 0.49 in a tandem mass spectrometry analysis and an elevated ammonia level of $537{\mu}mol/L$. Urine organic acid analysis showed increased excretion of methylmalonate. Subsequent sequence analysis of the methylmalonyl-CoA mutase (MUT) gene revealed compound heterozygous mutations c.323G>A (p.Arg108His) in exon 1 and c.1033_1034del (p. Leu345Serfs*15) in exon 4, the latter being a novel mutation. In summary, this is the first case of MMA and cardiomyopathy in Korea that was confirmed by genetic analysis to involve a novel MUT mutation.

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References

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