Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening
Abstract Background Primary carnitine deficiency (PCD) is an autosomal recessive disorder of carnitine transportation that leads to impaired fatty acid oxidation. Large-scale studies on newborn screening (NBS) for PCD are limited. This study aimed to investigate the biochemical and genetic character...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-021-02126-3 |
| _version_ | 1818405354455695360 |
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| author | Yiming Lin Bangbang Lin Yanru Chen Zhenzhu Zheng Qingliu Fu Weihua Lin Weifeng Zhang |
| author_facet | Yiming Lin Bangbang Lin Yanru Chen Zhenzhu Zheng Qingliu Fu Weihua Lin Weifeng Zhang |
| author_sort | Yiming Lin |
| collection | DOAJ |
| description | Abstract Background Primary carnitine deficiency (PCD) is an autosomal recessive disorder of carnitine transportation that leads to impaired fatty acid oxidation. Large-scale studies on newborn screening (NBS) for PCD are limited. This study aimed to investigate the biochemical and genetic characteristics of patients with PCD detected through NBS. Results A total of 548 247 newborns were screened for PCD between January 2014 and June 2021; 1714 newborns with low free carnitine (C0) levels were called back and 49 patients were diagnosed with PCD. The latest incidence rate in Quanzhou, China, was estimated to be 1 in 11 189 newborns. NBS results showed that the 49 patients had varying degrees of decreased C0 levels, whereas seven patients exhibited normal C0 levels during the recall review. All patients harbored biallelic pathogenic variants of the SLC22A5 gene. Nineteen distinct SLC22A5 variants were detected in these 49 patients, and most of the detected variants were clustered in exons 1, 4, and 7. The top eight variants had an allele frequency of 86.73%. The most common variant was c.760C > T (p.R254*) with an allele frequency of 31.63%, followed by c.51C > G (p.F17L) (17.35%) and c.1400C > G (p.S467C) (16.33%). The C0 level of patients with the N/N genotype was significantly lower than that of the M/M group. The C0 levels of patients with genotypes of R254*/R254* and R254*/F17L were far lower than those of patients with the R254*/S467C genotype. Conclusions This study presented more than 500,000 NBS data with the latest incidence of 1:11 189 in the Quanzhou area. The SLC22A5 variant spectrum in the selected southern Chinese population has been updated. Patients with null variants were associated with low C0 levels. Combining NBS with genetic testing is critical to improve screening efficiency because patients with PCD may have normal C0 levels during NBS and recall review. |
| first_indexed | 2024-12-14T08:54:43Z |
| format | Article |
| id | doaj.art-c08bc83234284ea583a2fc429935d36f |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-14T08:54:43Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-c08bc83234284ea583a2fc429935d36f2022-12-21T23:08:58ZengBMCOrphanet Journal of Rare Diseases1750-11722021-12-011611710.1186/s13023-021-02126-3Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screeningYiming Lin0Bangbang Lin1Yanru Chen2Zhenzhu Zheng3Qingliu Fu4Weihua Lin5Weifeng Zhang6Center of Neonatal Disease Screening, Quanzhou Maternity and Children’s HospitalAdministrative Office, Quanzhou Maternity and Children’s HospitalCenter of Neonatal Disease Screening, Quanzhou Maternity and Children’s HospitalCenter of Neonatal Disease Screening, Quanzhou Maternity and Children’s HospitalCenter of Neonatal Disease Screening, Quanzhou Maternity and Children’s HospitalCenter of Neonatal Disease Screening, Quanzhou Maternity and Children’s HospitalDepartment of Neonatology, Quanzhou Maternity and Children’s HospitalAbstract Background Primary carnitine deficiency (PCD) is an autosomal recessive disorder of carnitine transportation that leads to impaired fatty acid oxidation. Large-scale studies on newborn screening (NBS) for PCD are limited. This study aimed to investigate the biochemical and genetic characteristics of patients with PCD detected through NBS. Results A total of 548 247 newborns were screened for PCD between January 2014 and June 2021; 1714 newborns with low free carnitine (C0) levels were called back and 49 patients were diagnosed with PCD. The latest incidence rate in Quanzhou, China, was estimated to be 1 in 11 189 newborns. NBS results showed that the 49 patients had varying degrees of decreased C0 levels, whereas seven patients exhibited normal C0 levels during the recall review. All patients harbored biallelic pathogenic variants of the SLC22A5 gene. Nineteen distinct SLC22A5 variants were detected in these 49 patients, and most of the detected variants were clustered in exons 1, 4, and 7. The top eight variants had an allele frequency of 86.73%. The most common variant was c.760C > T (p.R254*) with an allele frequency of 31.63%, followed by c.51C > G (p.F17L) (17.35%) and c.1400C > G (p.S467C) (16.33%). The C0 level of patients with the N/N genotype was significantly lower than that of the M/M group. The C0 levels of patients with genotypes of R254*/R254* and R254*/F17L were far lower than those of patients with the R254*/S467C genotype. Conclusions This study presented more than 500,000 NBS data with the latest incidence of 1:11 189 in the Quanzhou area. The SLC22A5 variant spectrum in the selected southern Chinese population has been updated. Patients with null variants were associated with low C0 levels. Combining NBS with genetic testing is critical to improve screening efficiency because patients with PCD may have normal C0 levels during NBS and recall review.https://doi.org/10.1186/s13023-021-02126-3Primary carnitine deficiencyNewborn screeningSLC22A5 geneFree carnitineTandem mass spectrometry |
| spellingShingle | Yiming Lin Bangbang Lin Yanru Chen Zhenzhu Zheng Qingliu Fu Weihua Lin Weifeng Zhang Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening Orphanet Journal of Rare Diseases Primary carnitine deficiency Newborn screening SLC22A5 gene Free carnitine Tandem mass spectrometry |
| title | Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening |
| title_full | Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening |
| title_fullStr | Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening |
| title_full_unstemmed | Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening |
| title_short | Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening |
| title_sort | biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening |
| topic | Primary carnitine deficiency Newborn screening SLC22A5 gene Free carnitine Tandem mass spectrometry |
| url | https://doi.org/10.1186/s13023-021-02126-3 |
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