Novel and Recurrent ACADS Mutations and Clinical Manifestations Observed in Korean Patients with Short-chain Acyl-coenzyme a Dehydrogenase Deficiency

Short-chain acyl-CoA dehydrogenase (SCAD) catalyzes the first step in mitochondrial short-chain beta-oxidation, and its deficiency is caused by mutations in the ACADS. We sought to investigate the spectrum ACADS mutations and associated clinical manifestations in Korean patients with SCAD deficiency. The study included ten patients with SCAD deficiency from 8 unrelated families as diagnosed by biochemical profile and mutation analyses. Clinical features, biochemical data, growth, and neurodevelopmental state were reviewed retrospectively. Eight patients were found during newborn screening, and two were diagnosed by family screening. During follow-up ranging from 2 months to 4.5 years, no hypoglycemic event was noted, and the development and growth of the patients were normal, except in two siblings. One exhibited hypotonia and gross motor delay, while one girl showed cyclic vomiting until the age of two years. We identified seven different mutations of ACADS. Of these, p. E344G was the most frequent mutation with an allele frequency of 50%, followed by p. P55L with 18.8%. p. G108D and four novel mutations were identified: p. L93I, p. E228K, p. P377L, and p. R386H. Korean patients with SCAD deficiency showed heterogenous clinical features and ACADS genotype. Our data contributes to a better understanding of the distinct molecular genetic characteristics and clinical manifestations of SCAD deficiency.