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Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes?
Neonatal metabolic acidosis (NMA) is a common problem, particularly in critically ill patients in neonatal intensive care units (NICUs). Complex etiologies and atypical clinical signs make diagnosis difficult; thus, it is crucial to investigate the underlying causes of NMA rapidly and provide disord...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558493/ https://www.ncbi.nlm.nih.gov/pubmed/34733806 http://dx.doi.org/10.3389/fped.2021.727301 |
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author | Ma, Haiyan Tang, Zezhong Xiao, Feifan Li, Long Li, Yangfang Tang, Wenyan Chen, Liping Kang, Wenqing Lu, Yulan Dong, Xinran Cheng, Guoqiang Wang, Laishuan Lu, Wei Yang, Lin Ni, Qi Peng, Xiaomin Wang, Yao Cao, Yun Wu, Bingbing Zhou, Wenhao Zhuang, Deyi Lin, Guang Wang, Huijun |
author_facet | Ma, Haiyan Tang, Zezhong Xiao, Feifan Li, Long Li, Yangfang Tang, Wenyan Chen, Liping Kang, Wenqing Lu, Yulan Dong, Xinran Cheng, Guoqiang Wang, Laishuan Lu, Wei Yang, Lin Ni, Qi Peng, Xiaomin Wang, Yao Cao, Yun Wu, Bingbing Zhou, Wenhao Zhuang, Deyi Lin, Guang Wang, Huijun |
author_sort | Ma, Haiyan |
collection | PubMed |
description | Neonatal metabolic acidosis (NMA) is a common problem, particularly in critically ill patients in neonatal intensive care units (NICUs). Complex etiologies and atypical clinical signs make diagnosis difficult; thus, it is crucial to investigate the underlying causes of NMA rapidly and provide disorder-specific therapies. Our study aims to provide an overview of the genetic causes of NMA in patients from NICUs. We performed next-generation sequencing (NGS) on neonates with NMA from January 2016 to December 2019. Clinical features, genetic diagnoses, and their effects on clinical interventions were collected for analysis. In the 354 enrolled patients, 131 (37%) received genetic diagnoses; 95 (72.5%) of them were autosomal recessively inherited diseases. Two hundred and fifteen variants spanning 57 genes were classified as pathogenic (P) or likely pathogenic (LP) in 131 patients. The leading cause was metabolic disorders due to 35 genes found in 89 patients (68%). The other 42 NMA patients (32%) with 22 genes had malformations and renal, neuromuscular, and immune-hematological disorders. Seven genes (MMUT, MMACHC, CHD7, NPHS1, OTC, IVD, and PHOX2B) were noted in more than four patients, accounting for 48.9% (64/131) of the identified P/LP variants. Forty-six diagnosed patients with uncorrected NMA died or gave up. In conclusion, 37% of neonates with metabolic acidosis had genetic disorders. Next-generation sequencing should be considered when investigating the etiology of NMA in NICUs. Based on early molecular diagnoses, valuable treatment options can be provided for some genetic diseases to achieve better outcomes. |
format | Online Article Text |
id | pubmed-8558493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85584932021-11-02 Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes? Ma, Haiyan Tang, Zezhong Xiao, Feifan Li, Long Li, Yangfang Tang, Wenyan Chen, Liping Kang, Wenqing Lu, Yulan Dong, Xinran Cheng, Guoqiang Wang, Laishuan Lu, Wei Yang, Lin Ni, Qi Peng, Xiaomin Wang, Yao Cao, Yun Wu, Bingbing Zhou, Wenhao Zhuang, Deyi Lin, Guang Wang, Huijun Front Pediatr Pediatrics Neonatal metabolic acidosis (NMA) is a common problem, particularly in critically ill patients in neonatal intensive care units (NICUs). Complex etiologies and atypical clinical signs make diagnosis difficult; thus, it is crucial to investigate the underlying causes of NMA rapidly and provide disorder-specific therapies. Our study aims to provide an overview of the genetic causes of NMA in patients from NICUs. We performed next-generation sequencing (NGS) on neonates with NMA from January 2016 to December 2019. Clinical features, genetic diagnoses, and their effects on clinical interventions were collected for analysis. In the 354 enrolled patients, 131 (37%) received genetic diagnoses; 95 (72.5%) of them were autosomal recessively inherited diseases. Two hundred and fifteen variants spanning 57 genes were classified as pathogenic (P) or likely pathogenic (LP) in 131 patients. The leading cause was metabolic disorders due to 35 genes found in 89 patients (68%). The other 42 NMA patients (32%) with 22 genes had malformations and renal, neuromuscular, and immune-hematological disorders. Seven genes (MMUT, MMACHC, CHD7, NPHS1, OTC, IVD, and PHOX2B) were noted in more than four patients, accounting for 48.9% (64/131) of the identified P/LP variants. Forty-six diagnosed patients with uncorrected NMA died or gave up. In conclusion, 37% of neonates with metabolic acidosis had genetic disorders. Next-generation sequencing should be considered when investigating the etiology of NMA in NICUs. Based on early molecular diagnoses, valuable treatment options can be provided for some genetic diseases to achieve better outcomes. Frontiers Media S.A. 2021-10-18 /pmc/articles/PMC8558493/ /pubmed/34733806 http://dx.doi.org/10.3389/fped.2021.727301 Text en Copyright © 2021 Ma, Tang, Xiao, Li, Li, Tang, Chen, Kang, Lu, Dong, Cheng, Wang, Lu, Yang, Ni, Peng, Wang, Cao, Wu, Zhou, Zhuang, Lin and Wang. https://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 | Pediatrics Ma, Haiyan Tang, Zezhong Xiao, Feifan Li, Long Li, Yangfang Tang, Wenyan Chen, Liping Kang, Wenqing Lu, Yulan Dong, Xinran Cheng, Guoqiang Wang, Laishuan Lu, Wei Yang, Lin Ni, Qi Peng, Xiaomin Wang, Yao Cao, Yun Wu, Bingbing Zhou, Wenhao Zhuang, Deyi Lin, Guang Wang, Huijun Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes? |
title | Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes? |
title_full | Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes? |
title_fullStr | Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes? |
title_full_unstemmed | Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes? |
title_short | Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes? |
title_sort | neonatal metabolic acidosis in the neonatal intensive care unit: what are the genetic causes? |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558493/ https://www.ncbi.nlm.nih.gov/pubmed/34733806 http://dx.doi.org/10.3389/fped.2021.727301 |
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