PMID- 34733806 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211105 IS - 2296-2360 (Print) IS - 2296-2360 (Electronic) IS - 2296-2360 (Linking) VI - 9 DP - 2021 TI - Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes? PG - 727301 LID - 10.3389/fped.2021.727301 [doi] LID - 727301 AB - 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. CI - Copyright (c) 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. FAU - Ma, Haiyan AU - Ma H AD - Department of Neonatology, Zhuhai Women and Children's Hospital, Zhuhai, China. FAU - Tang, Zezhong AU - Tang Z AD - Department of Pediatrics, Peking University First Hospital, Beijing, China. FAU - Xiao, Feifan AU - Xiao F AD - Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. FAU - Li, Long AU - Li L AD - Department of Neonatology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China. FAU - Li, Yangfang AU - Li Y AD - Department of Neonatology, Kunming Children's Hospital, Kunming, China. FAU - Tang, Wenyan AU - Tang W AD - Department of Neonatology, Jiangxi Maternal Hospital, Nanchang, China. FAU - Chen, Liping AU - Chen L AD - Department of Neonatology, Jiangxi Provincial Children's Hospital, Nanchang, China. FAU - Kang, Wenqing AU - Kang W AD - Department of Neonatology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China. FAU - Lu, Yulan AU - Lu Y AD - Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. FAU - Dong, Xinran AU - Dong X AD - Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. FAU - Cheng, Guoqiang AU - Cheng G AD - Department of Neonatology, Children's Hospital of Fudan University, Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai, China. FAU - Wang, Laishuan AU - Wang L AD - Department of Neonatology, Children's Hospital of Fudan University, Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai, China. FAU - Lu, Wei AU - Lu W AD - Department of Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China. FAU - Yang, Lin AU - Yang L AD - Department of Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China. FAU - Ni, Qi AU - Ni Q AD - Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. FAU - Peng, Xiaomin AU - Peng X AD - Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. FAU - Wang, Yao AU - Wang Y AD - Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. FAU - Cao, Yun AU - Cao Y AD - Department of Neonatology, Children's Hospital of Fudan University, Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai, China. FAU - Wu, Bingbing AU - Wu B AD - Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. FAU - Zhou, Wenhao AU - Zhou W AD - Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. AD - Department of Neonatology, Children's Hospital of Fudan University, Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai, China. FAU - Zhuang, Deyi AU - Zhuang D AD - Xiamen Key Laboratory of Neonatal Diseases, Xiamen Children's Hospital, Xiamen, China. FAU - Lin, Guang AU - Lin G AD - Department of Neonatology, Zhuhai Women and Children's Hospital, Zhuhai, China. FAU - Wang, Huijun AU - Wang H AD - Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. LA - eng PT - Journal Article DEP - 20211018 PL - Switzerland TA - Front Pediatr JT - Frontiers in pediatrics JID - 101615492 PMC - PMC8558493 OTO - NOTNLM OT - gene OT - neonatal intensive care units OT - neonatal metabolic acidosis OT - neonate OT - next-generation sequencing COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/11/05 06:00 MHDA- 2021/11/05 06:01 PMCR- 2021/10/18 CRDT- 2021/11/04 06:27 PHST- 2021/06/18 00:00 [received] PHST- 2021/09/20 00:00 [accepted] PHST- 2021/11/04 06:27 [entrez] PHST- 2021/11/05 06:00 [pubmed] PHST- 2021/11/05 06:01 [medline] PHST- 2021/10/18 00:00 [pmc-release] AID - 10.3389/fped.2021.727301 [doi] PST - epublish SO - Front Pediatr. 2021 Oct 18;9:727301. doi: 10.3389/fped.2021.727301. eCollection 2021.