Xia Zhongmin, Wang Xudong, Ye Huiming, Gao Chunliu, Zhou Xiaoman, Chen Jing, Ge Yunsheng, Li Juan, Zhou Yulin, Guo Qiwei
United Diagnostic and Research Center for Clinical Genetics, Women and Children's Hospital, School of Medicine and School of Public Health, Xiamen University, Xiamen, Fujian, China.
Department of Clinical Laboratory, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Front Genet. 2022 Sep 23;13:844381. doi: 10.3389/fgene.2022.844381. eCollection 2022.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is caused by pathogenic variants of that result in decreased G6PD activity, is an X-linked inherited inborn error of metabolism that occurs worldwide. Individuals with G6PD deficiency and heterozygous females with normal G6PD activity (i.e., all individuals with pathogenic variants) are at risk of developing hemolytic anemia under increased oxidative challenge. However, this risk can be minimized by timely diagnosis. Currently, two assays are used to diagnose G6PD deficiency in China: evaluation of enzymatic activity and targeted genotyping. In terms of identification of all individuals with pathogenic variants, the performance and cost of different diagnostic strategies (isolated or combined evaluation of G6PD activity and genotyping) can vary, and these factors should be comprehensively evaluated. In this study, we examined 555 infants (437 males and 118 females) who were positive for the newborn screening of G6PD deficiency. We first evaluated the diagnostic performances of enzymatic testing and targeted genotyping. Both assays attained 100% specificities and positive predictive values for both male and female infants. In contrast, the sensitivities and negative predictive values (NPVs) of the diagnostic tests were different for male and female infants. For male infants, the sensitivities were 99.8 and 98.3%, and the NPVs were 94.1% and 69.6%, for enzymatic testing and targeted genotyping, respectively. For female infants, the sensitivities were 62.5% and 97.9%, and the NPVs were 37.9% and 91.7%, for enzymatic testing and targeted genotyping, respectively. We also evaluated the cost of the five different diagnostic strategies. The combination of G6PD activity testing of all infants, followed by genotyping of female infants with normal G6PD activity, attained high diagnostic sensitivity (99.8%) at a low cost (8.60 USD per diagnosed case). In the future, simultaneous examination of G6PD activity and whole-exon or whole-gene sequencing could become a standard clinical practice. Our data provide references for clinical practice on the standardization of current and future interventions for G6PD deficiency in China.
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症是一种X连锁遗传性先天性代谢缺陷病，由导致G6PD活性降低的致病变异引起，在全球范围内均有发生。G6PD缺乏症患者以及G6PD活性正常的杂合子女性（即所有携带致病变异的个体）在氧化应激增加的情况下有发生溶血性贫血的风险。然而，通过及时诊断可将这种风险降至最低。目前，中国有两种检测方法用于诊断G6PD缺乏症：酶活性评估和靶向基因分型。在识别所有携带致病变异的个体方面，不同诊断策略（单独或联合评估G6PD活性和基因分型）的性能和成本可能有所不同，这些因素应综合评估。在本研究中，我们检查了555名新生儿筛查G6PD缺乏症呈阳性的婴儿（437名男性和118名女性）。我们首先评估了酶检测和靶向基因分型的诊断性能。两种检测方法对男、女婴儿的特异性和阳性预测值均达到100%。相比之下，诊断测试的敏感性和阴性预测值在男、女婴儿中有所不同。对于男婴，酶检测和靶向基因分型的敏感性分别为99.8%和98.3%，阴性预测值分别为94.1%和69.6%。对于女婴，酶检测和靶向基因分型的敏感性分别为62.5%和97.9%，阴性预测值分别为37.9%和91.7%。我们还评估了五种不同诊断策略的成本。对所有婴儿进行G6PD活性检测，然后对G6PD活性正常的女婴进行基因分型，这种联合检测以低成本（每例确诊病例8.60美元）获得了较高的诊断敏感性（99.8%）。未来，同时检测G6PD活性和全外显子或全基因测序可能会成为标准的临床实践。我们的数据为中国目前和未来G6PD缺乏症干预措施标准化的临床实践提供了参考。
