Identification of a novel frameshift mutation (L345Sfs*15) in a Korean neonate with methylmalonic acidemia.
- Author:
Young A KIM
1
;
Ji Yong KIM
;
Yoo Mi KIM
;
Chong Kun CHEON
Author Information
- Publication Type:Case Report
- Keywords: Methylmalonic acidemia; Cardiomyopathies; MUT gene
- MeSH: 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
- From:Journal of Genetic Medicine 2017;14(2):80-85
- CountryRepublic of Korea
- Language:English
- 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.
