J Genet Med.  2012 Jun;9(1):42-46. 10.5734/JGM.2012.9.1.42.

Identification of Novel Compound Heterozygous Mutations in the ACADS Gene of an Asymptomatic Korean Newborn with Short Chain Acyl-CoA Dehydrogenase Deficiency by Tandem Mass Spectrometry

• Cheon CK
• Choi HS
• Kim SY
• Yoo HW
• Kim GH

• KMID: 2055570
• DOI: http://doi.org/10.5734/JGM.2012.9.1.42

Abstract

Short-chain acyl-CoA dehydrogenase deficiency (SCADD; OMIM # 201470) is an autosomal recessive inborn error of mitochondrial fatty acid beta-oxidation, presenting with a variety of clinical signs and symptoms. Developmental delay, hypertonia or hypotonia, ketotic hypoglycemia, and epilepsy are most frequently reported. In general, patients diagnosed through newborn screening have shown normal growth and development in contrast to those diagnosed as a result of clinically initiated evaluations. Here, the case of an asymptomatic Korean newborn with SCADD identified by tandem mass spectrometry is reported. The patient showed an elevated concentration of butyrylcarnitine detected on newborn screening. Urinary excretion of ethylmalonic acid was elevated by urine organic acid analysis. To confirm the diagnosis of SCADD, a direct sequencing analysis of 10 coding exons and the exon-intron boundaries of the ACADS gene were performed. Genetic analysis of ACADS showed the following novel compound heterozygous missense mutations: c.277C>A (p.Leu93Ile) on exon3 and c.682G>A (p.Glu288Lys) on exon6. These results will provide further evidence of mutational heterogeneity for SCADD.

Keyword

Short-chain acyl-CoA dehydrogenase deficiency; ACADS gene; Novel mutations; Tandem mass spectrometry

MeSH Terms

Acyl-CoA Dehydrogenase
Butyryl-CoA Dehydrogenase
Carnitine
Clinical Coding
Databases, Genetic
Epilepsy
Exons
Growth and Development
Humans
Hypoglycemia
Infant, Newborn
Malonates
Mass Screening
Muscle Hypotonia
Population Characteristics
Tandem Mass Spectrometry
Acyl-CoA Dehydrogenase
Butyryl-CoA Dehydrogenase
Carnitine
Malonates