Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China
Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disease caused by a defect of mitochondrial acetoacetyl-CoA thiolase. Beginning in 2014, we carried out newborn screening by tandem mass spectrometry (MS/MS) followed by next-generation sequencing (NGS) and identified two infants with BKT...
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2019.00451/full |
| _version_ | 1828521464090853376 |
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| author | Yuqi Yang Shu hong Jiang Shuang Liu Xiao ya Han Ying Wang Lei lei Wang Bin Yu |
| author_facet | Yuqi Yang Shu hong Jiang Shuang Liu Xiao ya Han Ying Wang Lei lei Wang Bin Yu |
| author_sort | Yuqi Yang |
| collection | DOAJ |
| description | Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disease caused by a defect of mitochondrial acetoacetyl-CoA thiolase. Beginning in 2014, we carried out newborn screening by tandem mass spectrometry (MS/MS) followed by next-generation sequencing (NGS) and identified two infants with BKTD among 203,750 newborns born in Jiangsu Province, China. Both infants showed the characteristic chemical abnormalities of BKTD. We used NGS to confirm variants in the ACAT1. Patient 1 had the compound heterozygous variants c.721dupA and c.928G > C. Patient 2 had compound heterozygosity for the c.238+1G > A and c.1163G > T variants. c.721dupA, c.928G > C and c.1163G > T were suspected to be likely pathogenic, whereas c.238+1G > A was determined to be pathogenic. None of the four variants have been reported in the literature. Patient 1 presented with onset of metabolic acidosis and neonatal hypoglycemia 8 days after birth, whereas patient 2 was detected through neonatal disease screening but had no clinical manifestations. These findings contribute to our understanding of the clinical characteristics and genetic basis of BKTD. |
| first_indexed | 2024-12-11T19:49:18Z |
| format | Article |
| id | doaj.art-545d48c3fd974c4faa467d784ce2e784 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-11T19:49:18Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-545d48c3fd974c4faa467d784ce2e7842022-12-22T00:52:48ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-05-011010.3389/fgene.2019.00451449845Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in ChinaYuqi Yang0Shu hong Jiang1Shuang Liu2Xiao ya Han3Ying Wang4Lei lei Wang5Bin Yu6Changzhou Maternity and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaChangzhou Maternity and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaLianyungang Maternal and Child Health Hospital, Yangzhou University, Lianyungang, ChinaChangzhou Maternity and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaChangzhou Maternity and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaLianyungang Maternal and Child Health Hospital, Yangzhou University, Lianyungang, ChinaChangzhou Maternity and Child Health Care Hospital, Nanjing Medical University, Changzhou, ChinaBeta-ketothiolase deficiency (BKTD) is an autosomal recessive disease caused by a defect of mitochondrial acetoacetyl-CoA thiolase. Beginning in 2014, we carried out newborn screening by tandem mass spectrometry (MS/MS) followed by next-generation sequencing (NGS) and identified two infants with BKTD among 203,750 newborns born in Jiangsu Province, China. Both infants showed the characteristic chemical abnormalities of BKTD. We used NGS to confirm variants in the ACAT1. Patient 1 had the compound heterozygous variants c.721dupA and c.928G > C. Patient 2 had compound heterozygosity for the c.238+1G > A and c.1163G > T variants. c.721dupA, c.928G > C and c.1163G > T were suspected to be likely pathogenic, whereas c.238+1G > A was determined to be pathogenic. None of the four variants have been reported in the literature. Patient 1 presented with onset of metabolic acidosis and neonatal hypoglycemia 8 days after birth, whereas patient 2 was detected through neonatal disease screening but had no clinical manifestations. These findings contribute to our understanding of the clinical characteristics and genetic basis of BKTD.https://www.frontiersin.org/article/10.3389/fgene.2019.00451/fullnewborn screeninginborn errors of metabolismtandem mass spectrometrybeta-ketothiolase deficiencynext-generation sequencingACAT1 |
| spellingShingle | Yuqi Yang Shu hong Jiang Shuang Liu Xiao ya Han Ying Wang Lei lei Wang Bin Yu Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China Frontiers in Genetics newborn screening inborn errors of metabolism tandem mass spectrometry beta-ketothiolase deficiency next-generation sequencing ACAT1 |
| title | Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China |
| title_full | Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China |
| title_fullStr | Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China |
| title_full_unstemmed | Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China |
| title_short | Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China |
| title_sort | two infants with beta ketothiolase deficiency identified by newborn screening in china |
| topic | newborn screening inborn errors of metabolism tandem mass spectrometry beta-ketothiolase deficiency next-generation sequencing ACAT1 |
| url | https://www.frontiersin.org/article/10.3389/fgene.2019.00451/full |
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