J Genet Med.  2017 Dec;14(2):80-85. 10.5734/JGM.2017.14.2.80.

Identification of a novel frameshift mutation (L345Sfs*15) in a Korean neonate with methylmalonic acidemia

• Kim YA
• Kim JY
• Kim YM
• Cheon CK

• KMID: 2401811
• DOI: http://doi.org/10.5734/JGM.2017.14.2.80

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 µmol/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.

Keyword

Methylmalonic acidemia; Cardiomyopathies; MUT gene

MeSH Terms

Ammonia
Body Fluids
Cardiomyopathies
Death, Sudden
Exons
Frameshift Mutation*
Heart Diseases
Humans
Hyperhomocysteinemia
Infant, Newborn*
Korea
Lethargy
Methylmalonyl-CoA Mutase
Plasma
Sequence Analysis
Tandem Mass Spectrometry
Vomiting
Ammonia
Methylmalonyl-CoA Mutase