Original Research ARTICLE
Biochemical, clinical, and genetic characteristics of short/branched chain acyl-CoA dehydrogenase deficiency in Chinese patients by newborn screening
- 1Quanzhou Maternal and Child Health Hospital, China
- 2Second Affiliated Hospital, Fujian Medical University, China
- 3Genuine Diagnostics Company Limited, China
Short/branched chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive disorder of impaired isoleucine catabolism caused by mutations in the ACADSB gene. There are limited SBCADD cases worldwide and to date no Chinese patients with SBCADD have been reported. The aim of this study was to investigate the biochemical, clinical information, and genotypes of twelve patients with SBCADD in China for the first time. The estimated incidence of SBCADD was 1 in 30,379 in Quanzhou, China. The initial newborn screening (NBS) results revealed that all patients showed slightly or moderately elevated C5 concentrations with C5/C2 and C5/C3 ratios in the reference range, which has the highest risk of being missed. All patients who underwent urinary organic acid analysis showed elevation of 2-methylburtyrylglycine in urine. All patients were asymptomatic at diagnosis, and had normal growth and development during follow-up. Eight different variants in the ACADSB gene, including five previously unreported variants were identified, namely c.596A>G (p.Tyr199Cys), c.653T>C (p.Leu218Pro), c.746del (p.Pro249Leufs*15), c.886G>T (p.Gly296*) and c.923G>A (p.Cys308Tyr). The most common variant was c.1165A>G (33.3%), followed by c.275C>G (20.8%). All previously unreported variants may cause structural damage and dysfunction of SBCAD, as predicted by bioinformatics analysis. Thus, our findings indicate that SBCADD may be more frequent in the Chinese population than previously thought and newborn screening, combined with genetic testing is important for timely diagnosis. Although the clinical course of Chinese patients with SBCADD is likely benign, longitudinal follow-up may be helpful to better understand the natural history of SBCADD.
Keywords: Short/branched chain acyl-CoA dehydrogenase deficiency, 2-methylbutyryl-CoA dehydrogenase deficiency, ACADSB gene, Newborn screening, Isoleucine catabolism
Received: 27 Dec 2018;
Accepted: 31 Jul 2019.
Edited by:Merlin G. Butler, University of Kansas Medical Center, United States
Reviewed by:Theodora Katsila, National Hellenic Research Foundation, Greece
Jerry Vockley, University of Pittsburgh Medical Center, Italy
Copyright: © 2019 Lin, Gao, Lin, Zhou, Chen, Lin, Zheng, Li, Li and Fu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Ms. Min Li, Genuine Diagnostics Company Limited, Hangzhou, China, firstname.lastname@example.org
Prof. Qingliu Fu, Quanzhou Maternal and Child Health Hospital, Quanzhou, Fujian Province, China, email@example.com