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

• Published in: Journal of genetic medicine Vol. 9; no. 1; pp. 42 - 66
• Main Authors: Cheon, Chong Kun, Choi, Hyung Soon, Kim, Su-Yung, Yoo, Han-Wook, Kim, Gu-Hwan
• Format: Journal Article
• Language: English
• Published: 대한의학유전학회 30.06.2012
• Subjects: 의학일반
• ISSN: 1226-1769; 2383-8442
• DOI: 10.5734/JGM.2012.9.1.42

Short-chain acyl-CoA dehydrogenase deficiency (SCADD; OMIM # 201470) is an autosomal recessive inborn error of mitochondrial fatty acid β-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. KCI Citation Count: 1