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Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China
Background: Primary carnitine deficiency (PCD) is an autosomal recessive disease caused by mutations in the SLC22A5 gene, which encodes the organic cation transporter 2 (OCTN2). Patients with PCD may be at risk of skeletal or cardiac myopathy, metabolic decompensation, and even sudden death. This st...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772520/ https://www.ncbi.nlm.nih.gov/pubmed/36568374 http://dx.doi.org/10.3389/fgene.2022.1062715 |
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author | Chang, Siyu Yang, Yi Xu, Feng Ji, Wenjun Zhan, Xia Gao, Xiaolan Chen, Ting Qiu, Wenjuan Zhang, Huiwen Liang, Lili Lu, Deyun Zhang, Kaichuang Gu, Xuefan Han, Lianshu |
author_facet | Chang, Siyu Yang, Yi Xu, Feng Ji, Wenjun Zhan, Xia Gao, Xiaolan Chen, Ting Qiu, Wenjuan Zhang, Huiwen Liang, Lili Lu, Deyun Zhang, Kaichuang Gu, Xuefan Han, Lianshu |
author_sort | Chang, Siyu |
collection | PubMed |
description | Background: Primary carnitine deficiency (PCD) is an autosomal recessive disease caused by mutations in the SLC22A5 gene, which encodes the organic cation transporter 2 (OCTN2). Patients with PCD may be at risk of skeletal or cardiac myopathy, metabolic decompensation, and even sudden death. This study aimed to analyze the biochemical, clinical, and genetic characteristics of PCD patients identified by newborn screening (NBS) in Shanghai. Methods: Dried blood spot (DBS) samples of newborns were analyzed through tandem mass spectrometry (MS/MS) from January 2003 to December 2021. Newborns with low free carnitine (C0) levels were recalled. Mutation in the SLC22A5 gene was analyzed on suspected positive newborns with low C0 levels after recall. Results: 1,247,274 newborns were screened by MS/MS and 40 newborns were diagnosed with PCD, therefore the incidence of PCD in Shanghai was approximately 1:31,200. The mean C0 level in newborns with PCD was 5.37 ± 1.79 μmol/L before treatment and increased to 24.45 ± 10.87 μmol/L after treatment with L-carnitine. Twenty-three different variants were identified in the SLC22A5 gene, including 8 novel variants, of which c.51C>G (p.F17L) was the most frequent (27.27%, 18/66), followed by c.1400C>G (p.S467C) (25.76%, 17/66). Almost all the screened PCD patients were asymptomatic. Conclusion: NBS via MS/MS was a quick and efficient method for the early diagnosis of PCD. The incidence of PCD in Shanghai was 1:31,200. Eight novel variants were identified, which greatly expanded the variant spectrum of SLC22A5. MS/MS combined with genetic testing could effectively improve the diagnostic accuracy of PCD. |
format | Online Article Text |
id | pubmed-9772520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97725202022-12-23 Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China Chang, Siyu Yang, Yi Xu, Feng Ji, Wenjun Zhan, Xia Gao, Xiaolan Chen, Ting Qiu, Wenjuan Zhang, Huiwen Liang, Lili Lu, Deyun Zhang, Kaichuang Gu, Xuefan Han, Lianshu Front Genet Genetics Background: Primary carnitine deficiency (PCD) is an autosomal recessive disease caused by mutations in the SLC22A5 gene, which encodes the organic cation transporter 2 (OCTN2). Patients with PCD may be at risk of skeletal or cardiac myopathy, metabolic decompensation, and even sudden death. This study aimed to analyze the biochemical, clinical, and genetic characteristics of PCD patients identified by newborn screening (NBS) in Shanghai. Methods: Dried blood spot (DBS) samples of newborns were analyzed through tandem mass spectrometry (MS/MS) from January 2003 to December 2021. Newborns with low free carnitine (C0) levels were recalled. Mutation in the SLC22A5 gene was analyzed on suspected positive newborns with low C0 levels after recall. Results: 1,247,274 newborns were screened by MS/MS and 40 newborns were diagnosed with PCD, therefore the incidence of PCD in Shanghai was approximately 1:31,200. The mean C0 level in newborns with PCD was 5.37 ± 1.79 μmol/L before treatment and increased to 24.45 ± 10.87 μmol/L after treatment with L-carnitine. Twenty-three different variants were identified in the SLC22A5 gene, including 8 novel variants, of which c.51C>G (p.F17L) was the most frequent (27.27%, 18/66), followed by c.1400C>G (p.S467C) (25.76%, 17/66). Almost all the screened PCD patients were asymptomatic. Conclusion: NBS via MS/MS was a quick and efficient method for the early diagnosis of PCD. The incidence of PCD in Shanghai was 1:31,200. Eight novel variants were identified, which greatly expanded the variant spectrum of SLC22A5. MS/MS combined with genetic testing could effectively improve the diagnostic accuracy of PCD. Frontiers Media S.A. 2022-12-08 /pmc/articles/PMC9772520/ /pubmed/36568374 http://dx.doi.org/10.3389/fgene.2022.1062715 Text en Copyright © 2022 Chang, Yang, Xu, Ji, Zhan, Gao, Chen, Qiu, Zhang, Liang, Lu, Zhang, Gu and Han. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Chang, Siyu Yang, Yi Xu, Feng Ji, Wenjun Zhan, Xia Gao, Xiaolan Chen, Ting Qiu, Wenjuan Zhang, Huiwen Liang, Lili Lu, Deyun Zhang, Kaichuang Gu, Xuefan Han, Lianshu Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China |
title | Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China |
title_full | Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China |
title_fullStr | Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China |
title_full_unstemmed | Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China |
title_short | Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China |
title_sort | clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in shanghai, china |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772520/ https://www.ncbi.nlm.nih.gov/pubmed/36568374 http://dx.doi.org/10.3389/fgene.2022.1062715 |
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