Objective: To analyze the screening results of glucose-6-phosphate dehydrogenase (G6PD) deficiency and gene mutation distribution of G6PD deficiency in preterm infants in Chengdu, China, in order to provide a basis for the improvement of G6PD screening process in preterm infants.
Methods: Fluorescent spot test for G6PD deficiency using dried blood spots was used for G6PD screening of 54 025 preterm infants born from January 1, 2015 to December 31, 2019 in Chengdu, and G6PD enzymology and gene detection were used for the diagnosis of 213 infants with positive screening results.
Results: Among the 54 025 preterm infants, 192 were diagnosed with G6PD deficiency, with an incidence rate of 3.55‰. The incidence rate of G6PD deficiency in preterm infants was higher than that in full-term infants in the same period of time and tended to increase year by year. Birth in summer, gestational age <32 weeks, and birth weight <2 500 g were influencing factors for the increase in false positive rate of screening (P < 0.05). The diagnostic accordance rate of genetic tests was significantly higher than that of enzyme activity assay in female infants (P < 0.05). Nine gene mutations were detected in Chengdu, without compound heterozygous mutation. Homozygous mutation was not detected in female infants. In the 80 infants with gene mutations, the top three gene mutations were c.1388G>A in 26 infants (32%), c.1376G>T in 21 infants (26%), and c.1024C>T in 13 infants (16%), accounting for 75%. There was a significant difference in pathogenicity grading among the three gene mutations (P < 0.001). The pairwise comparison showed that c.1024C>T had a significantly lower pathogenicity grade than c.1376G>T and c.1388G>A (P < 0.0167), suggesting that c.1376G>T and c.1388G>A had greater influence on enzyme activity than c.1024C>T.
Conclusions: Screening for G6PD deficiency in preterm infants should be taken seriously. It is recommended to apply cold-chain transportation of samples in summer to reduce the false positive rate of primary screening for G6PD deficiency. Genetic tests should be promoted in girls with positive screening results to improve the detection rate of G6PD deficiency in preterm female infants. There are various types of gene mutations in preterm infants with G6PD deficiency in Chengdu, and infants with c.1024C>T mutation tend to have mild conditions.
目的: 分析成都市早产儿葡萄糖-6-磷酸脱氢酶（glucose-6-phosphate dehydrogenase，G6PD）缺乏症筛查结果及基因突变分布情况，探讨早产儿人群G6PD筛查流程改进方案。
方法: 采用干血斑G6PD荧光分析法，对成都市2015年1月1日至2019年12月31日出生的54 025例早产儿足跟血样本进行G6PD缺乏症筛查，对213例筛查阳性患儿联合运用G6PD酶学和基因检测进行诊断分析。
结果: 在54 025例早产儿中，确诊G6PD缺乏症患儿192例，发病率为3.55‰。早产儿G6PD缺乏症的发病率高于同期足月儿，且有逐年增高趋势（P < 0.05）。夏季出生、胎龄 < 32周、出生体重 < 2 500 g为筛查假阳性率增加的影响因素（P < 0.05）。女性患儿基因检测法的确诊符合率高于酶活性检测法（P < 0.05）。成都地区共检出9种基因突变，未检出复合杂合突变，女性患儿未检出纯合突变。80例检出基因突变的患儿中，检出率最高的前3种基因突变类型为：c.1388G > A 26例（32%）、c.1376G > T 21例（26%）、c.1024C>T 13例（16%），共占比75%。3种基因突变类型的致病性分类情况差异有统计学意义（P < 0.001）；两两比较结果显示c.1024C>T比c.1376G > T、c.1388G > A基因突变的致病性分类程度更轻（P < 0.0167），提示c.1376G > T与c.1388G > A对G6PD酶活性的影响大于c.1024C>T。
结论: 应重视早产儿G6PD缺乏症筛查工作；建议夏季采用冷链运输标本以降低G6PD缺乏症筛查的初筛假阳性率；在女性筛查阳性儿中推广基因检测，以提高女性早产儿G6PD缺乏症检出率；成都地区早产儿G6PD缺乏症基因突变的类型呈多样化分布，c.1024C>T患儿病情程度较轻。