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Biochemical, Clinical, and Genetic Characteristics of Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients by Newborn Screening

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...

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Autores principales: Lin, Yiming, Gao, Hongzhi, Lin, Chunmei, Chen, Yanru, Zhou, Shuang, Lin, Weihua, Zheng, Zhenzhu, Li, Xiaoqing, Li, Min, Fu, Qingliu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727870/
https://www.ncbi.nlm.nih.gov/pubmed/31555323
http://dx.doi.org/10.3389/fgene.2019.00802
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author Lin, Yiming
Gao, Hongzhi
Lin, Chunmei
Chen, Yanru
Zhou, Shuang
Lin, Weihua
Zheng, Zhenzhu
Li, Xiaoqing
Li, Min
Fu, Qingliu
author_facet Lin, Yiming
Gao, Hongzhi
Lin, Chunmei
Chen, Yanru
Zhou, Shuang
Lin, Weihua
Zheng, Zhenzhu
Li, Xiaoqing
Li, Min
Fu, Qingliu
author_sort Lin, Yiming
collection PubMed
description 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.
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spelling pubmed-67278702019-09-25 Biochemical, Clinical, and Genetic Characteristics of Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients by Newborn Screening Lin, Yiming Gao, Hongzhi Lin, Chunmei Chen, Yanru Zhou, Shuang Lin, Weihua Zheng, Zhenzhu Li, Xiaoqing Li, Min Fu, Qingliu Front Genet Genetics 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. Frontiers Media S.A. 2019-08-28 /pmc/articles/PMC6727870/ /pubmed/31555323 http://dx.doi.org/10.3389/fgene.2019.00802 Text en Copyright © 2019 Lin, Gao, Lin, Chen, Zhou, Lin, Zheng, Li, Li and Fu http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Genetics
Lin, Yiming
Gao, Hongzhi
Lin, Chunmei
Chen, Yanru
Zhou, Shuang
Lin, Weihua
Zheng, Zhenzhu
Li, Xiaoqing
Li, Min
Fu, Qingliu
Biochemical, Clinical, and Genetic Characteristics of Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients by Newborn Screening
title Biochemical, Clinical, and Genetic Characteristics of Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients by Newborn Screening
title_full Biochemical, Clinical, and Genetic Characteristics of Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients by Newborn Screening
title_fullStr Biochemical, Clinical, and Genetic Characteristics of Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients by Newborn Screening
title_full_unstemmed Biochemical, Clinical, and Genetic Characteristics of Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients by Newborn Screening
title_short Biochemical, Clinical, and Genetic Characteristics of Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients by Newborn Screening
title_sort biochemical, clinical, and genetic characteristics of short/branched chain acyl-coa dehydrogenase deficiency in chinese patients by newborn screening
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727870/
https://www.ncbi.nlm.nih.gov/pubmed/31555323
http://dx.doi.org/10.3389/fgene.2019.00802
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