Prenatal Diagnosis of Glutaric Acidemia I Based on Amniotic Fluid Samples in 42 Families Using Genetic and Biochemical Approaches
Direct mutation analysis is the major method for glutaric acidemia I (GA-I) prenatal diagnosis, while systemic application of a biochemical strategy is rare. We describe our experiences with metabolite measurement together with mutation analysis in GA-I prenatal diagnosis at a single center over 10...
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.00496/full |
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| author | Bing Xiao Bing Xiao Wenjuan Qiu Wenjuan Qiu Jun Ye Jun Ye Huiwen Zhang Huiwen Zhang Hong Zhu Lei Wang Lili Liang Lili Liang Feng Xu Feng Xu Ting Chen Ting Chen Yan Xu Yan Xu Yongguo Yu Yongguo Yu Xuefan Gu Xuefan Gu Lianshu Han Lianshu Han |
| author_facet | Bing Xiao Bing Xiao Wenjuan Qiu Wenjuan Qiu Jun Ye Jun Ye Huiwen Zhang Huiwen Zhang Hong Zhu Lei Wang Lili Liang Lili Liang Feng Xu Feng Xu Ting Chen Ting Chen Yan Xu Yan Xu Yongguo Yu Yongguo Yu Xuefan Gu Xuefan Gu Lianshu Han Lianshu Han |
| author_sort | Bing Xiao |
| collection | DOAJ |
| description | Direct mutation analysis is the major method for glutaric acidemia I (GA-I) prenatal diagnosis, while systemic application of a biochemical strategy is rare. We describe our experiences with metabolite measurement together with mutation analysis in GA-I prenatal diagnosis at a single center over 10 years. The data of genetic analysis and metabolite measurement using gas chromatography/mass spectrometry(GC/MS) and tandem mass spectrometry(MS/MS) in amniotic fluid samples of 44 fetuses from 42 GA-I families referred to our center from 2009 to 2019 were retrospectively analyzed. Among these 44 fetuses, genetic and biochemical results were both available in 39 fetuses. Of these, 6 fetuses were judged as affected and 33 fetuses as unaffected by mutation analysis. The levels of glutarylcarnitine (C5DC), C5DC/octanoylcarnitine (C8), and glutaric acid in the supernatant of amniotic fluid from affected fetuses were significantly higher than those in unaffected fetuses [1.73μmol/L (0.89–4.19) vs. 0.16μmol/L (0.06–0.37), 26.26 (12.4–55.55) vs. 2.23 (1.04–8.44), and 103.94 mmol/mol creatinine (30.37–148.31) vs. 1.01mmol/mol creatinine (0–9.81), respectively; all P < 0.0001]. Among all families, two were found to have one causative mutation in the proband, in four pregnancies from these two families, three fetuses were judged as “unaffected” and one was judged as “affected” according to metabolites results. Postnatal follow-up showed a normal phenotype in all unaffected fetuses judged by mutation or metabolite analysis. C5DC, C5DC/C8, and glutaric acid levels in the supernatant of amniotic fluid showed significant differences and no overlap between the affected and unaffected fetuses. Biochemical strategy could be implemented as a quick and convenient method for the prenatal diagnosis of GA-I. |
| first_indexed | 2024-12-11T07:33:56Z |
| format | Article |
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| language | English |
| last_indexed | 2024-12-11T07:33:56Z |
| publishDate | 2020-05-01 |
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| spelling | doaj.art-fe50f9ce12ca46cf896ea08435c7b1262022-12-22T01:15:45ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-05-011110.3389/fgene.2020.00496541750Prenatal Diagnosis of Glutaric Acidemia I Based on Amniotic Fluid Samples in 42 Families Using Genetic and Biochemical ApproachesBing Xiao0Bing Xiao1Wenjuan Qiu2Wenjuan Qiu3Jun Ye4Jun Ye5Huiwen Zhang6Huiwen Zhang7Hong Zhu8Lei Wang9Lili Liang10Lili Liang11Feng Xu12Feng Xu13Ting Chen14Ting Chen15Yan Xu16Yan Xu17Yongguo Yu18Yongguo Yu19Xuefan Gu20Xuefan Gu21Lianshu Han22Lianshu Han23Department of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Institute of Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaCenter for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDirect mutation analysis is the major method for glutaric acidemia I (GA-I) prenatal diagnosis, while systemic application of a biochemical strategy is rare. We describe our experiences with metabolite measurement together with mutation analysis in GA-I prenatal diagnosis at a single center over 10 years. The data of genetic analysis and metabolite measurement using gas chromatography/mass spectrometry(GC/MS) and tandem mass spectrometry(MS/MS) in amniotic fluid samples of 44 fetuses from 42 GA-I families referred to our center from 2009 to 2019 were retrospectively analyzed. Among these 44 fetuses, genetic and biochemical results were both available in 39 fetuses. Of these, 6 fetuses were judged as affected and 33 fetuses as unaffected by mutation analysis. The levels of glutarylcarnitine (C5DC), C5DC/octanoylcarnitine (C8), and glutaric acid in the supernatant of amniotic fluid from affected fetuses were significantly higher than those in unaffected fetuses [1.73μmol/L (0.89–4.19) vs. 0.16μmol/L (0.06–0.37), 26.26 (12.4–55.55) vs. 2.23 (1.04–8.44), and 103.94 mmol/mol creatinine (30.37–148.31) vs. 1.01mmol/mol creatinine (0–9.81), respectively; all P < 0.0001]. Among all families, two were found to have one causative mutation in the proband, in four pregnancies from these two families, three fetuses were judged as “unaffected” and one was judged as “affected” according to metabolites results. Postnatal follow-up showed a normal phenotype in all unaffected fetuses judged by mutation or metabolite analysis. C5DC, C5DC/C8, and glutaric acid levels in the supernatant of amniotic fluid showed significant differences and no overlap between the affected and unaffected fetuses. Biochemical strategy could be implemented as a quick and convenient method for the prenatal diagnosis of GA-I.https://www.frontiersin.org/article/10.3389/fgene.2020.00496/fullglutaric acidemia Iprenatal diagnosisglutarylcarnitineglutaric acidmass spectrometry |
| spellingShingle | Bing Xiao Bing Xiao Wenjuan Qiu Wenjuan Qiu Jun Ye Jun Ye Huiwen Zhang Huiwen Zhang Hong Zhu Lei Wang Lili Liang Lili Liang Feng Xu Feng Xu Ting Chen Ting Chen Yan Xu Yan Xu Yongguo Yu Yongguo Yu Xuefan Gu Xuefan Gu Lianshu Han Lianshu Han Prenatal Diagnosis of Glutaric Acidemia I Based on Amniotic Fluid Samples in 42 Families Using Genetic and Biochemical Approaches Frontiers in Genetics glutaric acidemia I prenatal diagnosis glutarylcarnitine glutaric acid mass spectrometry |
| title | Prenatal Diagnosis of Glutaric Acidemia I Based on Amniotic Fluid Samples in 42 Families Using Genetic and Biochemical Approaches |
| title_full | Prenatal Diagnosis of Glutaric Acidemia I Based on Amniotic Fluid Samples in 42 Families Using Genetic and Biochemical Approaches |
| title_fullStr | Prenatal Diagnosis of Glutaric Acidemia I Based on Amniotic Fluid Samples in 42 Families Using Genetic and Biochemical Approaches |
| title_full_unstemmed | Prenatal Diagnosis of Glutaric Acidemia I Based on Amniotic Fluid Samples in 42 Families Using Genetic and Biochemical Approaches |
| title_short | Prenatal Diagnosis of Glutaric Acidemia I Based on Amniotic Fluid Samples in 42 Families Using Genetic and Biochemical Approaches |
| title_sort | prenatal diagnosis of glutaric acidemia i based on amniotic fluid samples in 42 families using genetic and biochemical approaches |
| topic | glutaric acidemia I prenatal diagnosis glutarylcarnitine glutaric acid mass spectrometry |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.00496/full |
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