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...

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Autores principales:	Yiming Lin, Bangbang Lin, Yanru Chen, Zhenzhu Zheng, Qingliu Fu, Weihua Lin, Weifeng Zhang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Primary carnitine deficiency Newborn screening SLC22A5 gene Free carnitine Tandem mass spectrometry Medicine R
Acceso en línea:	https://doaj.org/article/c08bc83234284ea583a2fc429935d36f
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spelling	oai:doaj.org-article:c08bc83234284ea583a2fc429935d36f2021-12-05T12:16:57ZBiochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening10.1186/s13023-021-02126-31750-1172https://doaj.org/article/c08bc83234284ea583a2fc429935d36f2021-12-01T00:00:00Zhttps://doi.org/10.1186/s13023-021-02126-3https://doaj.org/toc/1750-1172Abstract 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.Yiming LinBangbang LinYanru ChenZhenzhu ZhengQingliu FuWeihua LinWeifeng ZhangBMCarticlePrimary carnitine deficiencyNewborn screeningSLC22A5 geneFree carnitineTandem mass spectrometryMedicineRENOrphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Primary carnitine deficiency Newborn screening SLC22A5 gene Free carnitine Tandem mass spectrometry Medicine R
spellingShingle	Primary carnitine deficiency Newborn screening SLC22A5 gene Free carnitine Tandem mass spectrometry Medicine R 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
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.
format	article
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
title	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_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_sort	biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening
publisher	BMC
publishDate	2021
url	https://doaj.org/article/c08bc83234284ea583a2fc429935d36f
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_version_	1718372101396627456

Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening

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