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Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymatic defect. The purpose of this study was to evaluate the profile of G6PD deficiency and investigate the factors associated with the accuracy of newborn screening (NBS) in Xiamen, China. Methods: A total of 9...

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Autores principales: Wang, Xudong, Xia, Zhongmin, He, Ying, Zhou, Xiaoman, Zhang, Haixia, Gao, Chunliu, Ge, Yunsheng, Cai, Xiaofang, Zhou, Yulin, Guo, Qiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517332/
https://www.ncbi.nlm.nih.gov/pubmed/34659341
http://dx.doi.org/10.3389/fgene.2021.718503
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author Wang, Xudong
Xia, Zhongmin
He, Ying
Zhou, Xiaoman
Zhang, Haixia
Gao, Chunliu
Ge, Yunsheng
Cai, Xiaofang
Zhou, Yulin
Guo, Qiwei
author_facet Wang, Xudong
Xia, Zhongmin
He, Ying
Zhou, Xiaoman
Zhang, Haixia
Gao, Chunliu
Ge, Yunsheng
Cai, Xiaofang
Zhou, Yulin
Guo, Qiwei
author_sort Wang, Xudong
collection PubMed
description Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymatic defect. The purpose of this study was to evaluate the profile of G6PD deficiency and investigate the factors associated with the accuracy of newborn screening (NBS) in Xiamen, China. Methods: A total of 99,546 newborns were screened by modified fluorescent spot test at the Women and Children’s Hospital, Xiamen University. High-risk neonates were recalled for diagnosis by either a measurement of G6PD activity or genetic testing for the presence of pathogenic G6PD variants using a quantitative G6PD enzymatic assay or the MeltPro® G6PD assay, respectively. Results: In the first-tier screening, 1,256 newborns were categorized as high risk. Of these, 1,051 were diagnosed with G6PD deficiency, indicating a prevalence of 1.39% in Xiamen, China. Among the 1,013 neonates who underwent genotyping, 851 carried hemizygous, heterozygous, homozygous, or compound heterozygous variants, for a positive predictive value (PPV) of 84.01%. In total, 12 variants and 32 genotypes were identified, and the six most common variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.871G>A, and c.392G>T, which accounted for approximately 94% of the identified alleles. Different variants showed characteristic enzymatic activities, although high phenotypic heterogeneity was observed for each variant. The use of cold-chain transportation significantly improved the PPV of NBS. Conclusions: We determined the profile of G6PD deficiency in Xiamen, including the prevalence, variant spectrum, and genotype-phenotype correlations and confirmed that maintaining a low temperature during sample transport is essential to ensure the high screening accuracy of NBS. Our data provides epidemiological, genotypic, phenotypic, and clinical practice references to standardize future interventions for G6PD deficiency.
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spelling pubmed-85173322021-10-16 Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations Wang, Xudong Xia, Zhongmin He, Ying Zhou, Xiaoman Zhang, Haixia Gao, Chunliu Ge, Yunsheng Cai, Xiaofang Zhou, Yulin Guo, Qiwei Front Genet Genetics Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymatic defect. The purpose of this study was to evaluate the profile of G6PD deficiency and investigate the factors associated with the accuracy of newborn screening (NBS) in Xiamen, China. Methods: A total of 99,546 newborns were screened by modified fluorescent spot test at the Women and Children’s Hospital, Xiamen University. High-risk neonates were recalled for diagnosis by either a measurement of G6PD activity or genetic testing for the presence of pathogenic G6PD variants using a quantitative G6PD enzymatic assay or the MeltPro® G6PD assay, respectively. Results: In the first-tier screening, 1,256 newborns were categorized as high risk. Of these, 1,051 were diagnosed with G6PD deficiency, indicating a prevalence of 1.39% in Xiamen, China. Among the 1,013 neonates who underwent genotyping, 851 carried hemizygous, heterozygous, homozygous, or compound heterozygous variants, for a positive predictive value (PPV) of 84.01%. In total, 12 variants and 32 genotypes were identified, and the six most common variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.871G>A, and c.392G>T, which accounted for approximately 94% of the identified alleles. Different variants showed characteristic enzymatic activities, although high phenotypic heterogeneity was observed for each variant. The use of cold-chain transportation significantly improved the PPV of NBS. Conclusions: We determined the profile of G6PD deficiency in Xiamen, including the prevalence, variant spectrum, and genotype-phenotype correlations and confirmed that maintaining a low temperature during sample transport is essential to ensure the high screening accuracy of NBS. Our data provides epidemiological, genotypic, phenotypic, and clinical practice references to standardize future interventions for G6PD deficiency. Frontiers Media S.A. 2021-10-01 /pmc/articles/PMC8517332/ /pubmed/34659341 http://dx.doi.org/10.3389/fgene.2021.718503 Text en Copyright © 2021 Wang, Xia, He, Zhou, Zhang, Gao, Ge, Cai, Zhou and Guo. 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
Wang, Xudong
Xia, Zhongmin
He, Ying
Zhou, Xiaoman
Zhang, Haixia
Gao, Chunliu
Ge, Yunsheng
Cai, Xiaofang
Zhou, Yulin
Guo, Qiwei
Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations
title Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations
title_full Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations
title_fullStr Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations
title_full_unstemmed Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations
title_short Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations
title_sort newborn screening for g6pd deficiency in xiamen, china: prevalence, variant spectrum, and genotype-phenotype correlations
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517332/
https://www.ncbi.nlm.nih.gov/pubmed/34659341
http://dx.doi.org/10.3389/fgene.2021.718503
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