Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening
Primary carnitine deficiency (PCD) caused by pathogenic variants in the solute carrier family 22 member 5 (SLC22A5) gene is a rare autosomal recessive disease that results in defective fatty acid oxidation. PCD can be detected through tandem mass spectrometry (MS/MS), but transplacental transport of...
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| Format: | Article |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1304458/full |
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| author | Xiaoshan Ji Xiaoshan Ji Yanzhuang Ge Yanzhuang Ge Qi Ni Suhua Xu Zhongmeng Xiong Zhongmeng Xiong Lin Yang Liyuan Hu Yun Cao Yulan Lu Qiufen Wei Wenqing Kang Deyi Zhuang Wenhao Zhou Wenhao Zhou Wenhao Zhou Wenhao Zhou Xinran Dong |
| author_facet | Xiaoshan Ji Xiaoshan Ji Yanzhuang Ge Yanzhuang Ge Qi Ni Suhua Xu Zhongmeng Xiong Zhongmeng Xiong Lin Yang Liyuan Hu Yun Cao Yulan Lu Qiufen Wei Wenqing Kang Deyi Zhuang Wenhao Zhou Wenhao Zhou Wenhao Zhou Wenhao Zhou Xinran Dong |
| author_sort | Xiaoshan Ji |
| collection | DOAJ |
| description | Primary carnitine deficiency (PCD) caused by pathogenic variants in the solute carrier family 22 member 5 (SLC22A5) gene is a rare autosomal recessive disease that results in defective fatty acid oxidation. PCD can be detected through tandem mass spectrometry (MS/MS), but transplacental transport of free carnitine from mothers may cause false negatives or positives during newborn screening (NBS). This study aimed to analyze the genetic characteristics of SLC22A5 and estimate the prevalence of PCD in the Chinese population, providing useful information for NBS and genetic counseling. We manually curated SLC22A5 pathogenic or likely pathogenic (P/LP) variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines and identified 128 P/LP variants. Based on the China Neonatal Genomes Project (CNGP), the estimated PCD prevalence was 1:17,456, which was higher than that in other populations. The genotype–phenotype association analysis showed that patients carrying homozygous c.760C>T and c.844C>T were more likely to present cardiomyopathy, whereas those carrying homozygous c.1400C>G were more likely to be asymptomatic (all p-values < 0.05). We found that there was no significant difference in initial C0 concentrations between patients and carriers, but there was a significant difference in the second-tier screening of C0 concentration between them (p-value < 0.05). We established a cost-effective variant panel containing 10 high-frequency sites and developed a screening algorithm incorporating gene panels with MS/MS, which could rescue one more patient who was undetected from MS/MS. In conclusion, the prevalence of PCD in the Chinese population is relatively high. The combination of conventional NBS with genetic sequencing is suggested for early diagnosis of PCD. |
| first_indexed | 2024-03-09T02:38:20Z |
| format | Article |
| id | doaj.art-5f3c68adea68453ea7eb5ba93262620c |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-09T02:38:20Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-5f3c68adea68453ea7eb5ba93262620c2023-12-06T08:08:04ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-12-011410.3389/fgene.2023.13044581304458Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screeningXiaoshan Ji0Xiaoshan Ji1Yanzhuang Ge2Yanzhuang Ge3Qi Ni4Suhua Xu5Zhongmeng Xiong6Zhongmeng Xiong7Lin Yang8Liyuan Hu9Yun Cao10Yulan Lu11Qiufen Wei12Wenqing Kang13Deyi Zhuang14Wenhao Zhou15Wenhao Zhou16Wenhao Zhou17Wenhao Zhou18Xinran Dong19Center for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDivision of Neonatology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaChildren’s Hospital of Shanghai, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDivision of Neonatology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDivision of Neonatology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDivision of Neonatology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDivision of Neonatology, Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDivision of Neonatology, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, ChinaDivision of Pediatrics, Xiamen Children’s Hospital, Xiamen, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDivision of Neonatology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaGuangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaPrimary carnitine deficiency (PCD) caused by pathogenic variants in the solute carrier family 22 member 5 (SLC22A5) gene is a rare autosomal recessive disease that results in defective fatty acid oxidation. PCD can be detected through tandem mass spectrometry (MS/MS), but transplacental transport of free carnitine from mothers may cause false negatives or positives during newborn screening (NBS). This study aimed to analyze the genetic characteristics of SLC22A5 and estimate the prevalence of PCD in the Chinese population, providing useful information for NBS and genetic counseling. We manually curated SLC22A5 pathogenic or likely pathogenic (P/LP) variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines and identified 128 P/LP variants. Based on the China Neonatal Genomes Project (CNGP), the estimated PCD prevalence was 1:17,456, which was higher than that in other populations. The genotype–phenotype association analysis showed that patients carrying homozygous c.760C>T and c.844C>T were more likely to present cardiomyopathy, whereas those carrying homozygous c.1400C>G were more likely to be asymptomatic (all p-values < 0.05). We found that there was no significant difference in initial C0 concentrations between patients and carriers, but there was a significant difference in the second-tier screening of C0 concentration between them (p-value < 0.05). We established a cost-effective variant panel containing 10 high-frequency sites and developed a screening algorithm incorporating gene panels with MS/MS, which could rescue one more patient who was undetected from MS/MS. In conclusion, the prevalence of PCD in the Chinese population is relatively high. The combination of conventional NBS with genetic sequencing is suggested for early diagnosis of PCD.https://www.frontiersin.org/articles/10.3389/fgene.2023.1304458/fullprimary carnitine deficiencySLC22A5prevalence estimationnewborn screeninggenotype–phenotype analysis |
| spellingShingle | Xiaoshan Ji Xiaoshan Ji Yanzhuang Ge Yanzhuang Ge Qi Ni Suhua Xu Zhongmeng Xiong Zhongmeng Xiong Lin Yang Liyuan Hu Yun Cao Yulan Lu Qiufen Wei Wenqing Kang Deyi Zhuang Wenhao Zhou Wenhao Zhou Wenhao Zhou Wenhao Zhou Xinran Dong Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening Frontiers in Genetics primary carnitine deficiency SLC22A5 prevalence estimation newborn screening genotype–phenotype analysis |
| title | Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening |
| title_full | Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening |
| title_fullStr | Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening |
| title_full_unstemmed | Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening |
| title_short | Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening |
| title_sort | primary carnitine deficiency estimation of prevalence in chinese population and insights into newborn screening |
| topic | primary carnitine deficiency SLC22A5 prevalence estimation newborn screening genotype–phenotype analysis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1304458/full |
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