Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency
Introduction: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a pan-ethnic complicated inborn error of metabolism but the specific mechanism is not fully understood.Methods: A total of 169 patients with NICCD who have biallelic pathogenic SLC25A13 variants detected by target...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.939837/full |
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| author | Ting Zhang Shasha Zhu Haixia Miao Jianbin Yang Yezhen Shi Yuwei Yue Yu Zhang Rulai Yang Benqing Wu Xinwen Huang |
| author_facet | Ting Zhang Shasha Zhu Haixia Miao Jianbin Yang Yezhen Shi Yuwei Yue Yu Zhang Rulai Yang Benqing Wu Xinwen Huang |
| author_sort | Ting Zhang |
| collection | DOAJ |
| description | Introduction: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a pan-ethnic complicated inborn error of metabolism but the specific mechanism is not fully understood.Methods: A total of 169 patients with NICCD who have biallelic pathogenic SLC25A13 variants detected by targeted next-generation sequencing were collected. They were divided into the “Newborn-screen Group” and “Clinical diagnosed Group” depending on the newborn screening results. Amino acid and acylcarnitine profiles were measured by MS/MS. The total bile acids, blood amino acids and acylcarnitines, general biochemistry, blood count, and coagulation parameters were monitored every 2–3 months. We compared the differences in metabolic indices and their dynamic changes between these two groups. The Mann–Whitney test and orthogonal partial least squares discrimination analysis (OPLS-DA) were used for statistical analysis.Results: At the onset of NICCD, we found that the “Clinical diagnosed Group” had higher levels of intermediate products of the urea cycle, free carnitine, and short-chain and long-chain acylcarnitines than those in the “Newborn-screen Group,” but the levels of ketogenic/glucogenic amino acids and several medium-chain acylcarnitines were lower. Furthermore, concentrations of direct bilirubin, total bile acid, lactate, prothrombin time, and several liver enzymes were significantly higher while total protein, amylase, and hemoglobin were lower in the “Clinical diagnosed Group” than in the “Newborn-screen Group.” Dynamic change analysis showed that direct bilirubin, albumin, arginine, and citrulline were the earliest metabolic derangements to reach peak levels in NICCD groups, followed by acylcarnitine profiles, and finally with the elevation of liver enzymes. All abnormal characteristic metabolic indicators in the “Newborn-screen Group” came back to normal levels at earlier ages than the “Clinical diagnosed Group.” c.852_855del (41.2%), IVS16ins3kb (17.6%), c.615 + 5G>A (9.6%), 1638_1660dup (4.4%), and c.1177 + 1G>A (3.7%) accounted for 76.5% of all the mutated SLC25A13 alleles in our population.Conclusion: Argininosuccinate synthesis, gluconeogenesis, ketogenesis, fatty acid oxidation, liver function, and cholestasis were more severely affected in the “Clinical diagnosed Group.” The “Newborn-screen Group” had a better prognosis which highlighted the importance of newborn screening of NICCD. |
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| language | English |
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| spelling | doaj.art-41db918405e2496cb499eeb0cf52e4d52022-12-22T02:17:38ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-08-01910.3389/fmolb.2022.939837939837Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiencyTing Zhang0Shasha Zhu1Haixia Miao2Jianbin Yang3Yezhen Shi4Yuwei Yue5Yu Zhang6Rulai Yang7Benqing Wu8Xinwen Huang9Department of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, ChinaDepartment of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, ChinaDepartment of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, ChinaDepartment of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, ChinaDepartment of Technical Support, Zhejiang Biosan Biochemical Technologies Co. Ltd., Hangzhou, ChinaDepartment of Technical Support, Zhejiang Biosan Biochemical Technologies Co. Ltd., Hangzhou, ChinaDepartment of Technical Support, Zhejiang Biosan Biochemical Technologies Co. Ltd., Hangzhou, ChinaDepartment of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, ChinaDepartment of Neonatology, Children’s Medical Center, University of Chinese Academy of Science-Shenzhen Hospital, Shenzhen, ChinaDepartment of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, ChinaIntroduction: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a pan-ethnic complicated inborn error of metabolism but the specific mechanism is not fully understood.Methods: A total of 169 patients with NICCD who have biallelic pathogenic SLC25A13 variants detected by targeted next-generation sequencing were collected. They were divided into the “Newborn-screen Group” and “Clinical diagnosed Group” depending on the newborn screening results. Amino acid and acylcarnitine profiles were measured by MS/MS. The total bile acids, blood amino acids and acylcarnitines, general biochemistry, blood count, and coagulation parameters were monitored every 2–3 months. We compared the differences in metabolic indices and their dynamic changes between these two groups. The Mann–Whitney test and orthogonal partial least squares discrimination analysis (OPLS-DA) were used for statistical analysis.Results: At the onset of NICCD, we found that the “Clinical diagnosed Group” had higher levels of intermediate products of the urea cycle, free carnitine, and short-chain and long-chain acylcarnitines than those in the “Newborn-screen Group,” but the levels of ketogenic/glucogenic amino acids and several medium-chain acylcarnitines were lower. Furthermore, concentrations of direct bilirubin, total bile acid, lactate, prothrombin time, and several liver enzymes were significantly higher while total protein, amylase, and hemoglobin were lower in the “Clinical diagnosed Group” than in the “Newborn-screen Group.” Dynamic change analysis showed that direct bilirubin, albumin, arginine, and citrulline were the earliest metabolic derangements to reach peak levels in NICCD groups, followed by acylcarnitine profiles, and finally with the elevation of liver enzymes. All abnormal characteristic metabolic indicators in the “Newborn-screen Group” came back to normal levels at earlier ages than the “Clinical diagnosed Group.” c.852_855del (41.2%), IVS16ins3kb (17.6%), c.615 + 5G>A (9.6%), 1638_1660dup (4.4%), and c.1177 + 1G>A (3.7%) accounted for 76.5% of all the mutated SLC25A13 alleles in our population.Conclusion: Argininosuccinate synthesis, gluconeogenesis, ketogenesis, fatty acid oxidation, liver function, and cholestasis were more severely affected in the “Clinical diagnosed Group.” The “Newborn-screen Group” had a better prognosis which highlighted the importance of newborn screening of NICCD.https://www.frontiersin.org/articles/10.3389/fmolb.2022.939837/fullNICCDnewborn-screen groupclinical diagnosed groupmetabolic characteristicsprogressionprognosis |
| spellingShingle | Ting Zhang Shasha Zhu Haixia Miao Jianbin Yang Yezhen Shi Yuwei Yue Yu Zhang Rulai Yang Benqing Wu Xinwen Huang Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency Frontiers in Molecular Biosciences NICCD newborn-screen group clinical diagnosed group metabolic characteristics progression prognosis |
| title | Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency |
| title_full | Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency |
| title_fullStr | Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency |
| title_full_unstemmed | Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency |
| title_short | Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency |
| title_sort | dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency |
| topic | NICCD newborn-screen group clinical diagnosed group metabolic characteristics progression prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.939837/full |
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