Newborn screening for G6PD deficiency in HeFei, FuYang and AnQing, China: Prevalence, cut-off value, variant spectrum

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive Mendelian genetic disorder characterized by neonatal jaundice and hemolytic anemia, affecting more than 400 million people worldwide. The purpose of this research was to investigate prevalence rates of G6PD deficiency and to evaluate and establish specific cut-off values in early prediction of G6PD deficiency by regions (HeFei, FuYang, AnQing) on different seasons, as well as to investigate the frequencies of G6PD gene mutations among three regions mentioned above. Methods: A total of 31,482 neonates (21,402, 7680, and 2340 for HeFei, FuYang, and AnQing cities, respectively) were recruited. Positive subjects were recalled to attend genetic tests for diagnosis. G6PD activity on the Genetic screening processor (GSP analyzer, 2021-0010) was measured following the manufactureržs protocol. The cut-off value was first set to 35 U/dL. The receiver operating characteristics (ROC) curve was employed to assess and compare the efficiency in predicting G6PD deficiency among HeFei, FuYang, and AnQing cities in different seasons. Results: 31482 participants were screened for G6PD deficiency, and 29 neonates were finally identified with G6PD deficiency, with a prevalence rate of 0.09%. The incidence rate of the G6PD deficiency was 0.10% (22/21,380) for HeFei, 0.04%(3/7,667) for FuYang, and 0.17% (4/2,396) for AnQing. The optimal cut-off values of the ROC curve in the prediction of G6PD deficiency was 26.55 U/dL for HeFei (spring: 21.80 U/dL, summer: 26.55 U/dL, winter: 23.16 U/dL), 6.35 U/dL for FuYang, 7.15 U/dL for AnQing. R463H (17/57, 29.82%) was the most frequent variation, followed by R459L (15/57, 26.31%), H32R (8/57, 14.04%), L342F (6/57, 10.53%), V291M (6/57, 10.53%). Conclusion: We have established the optimal cut-off values of G6PD activity in predicting G6PD deficiency among HeFei, FuYang and AnQing in different seasons. This will aid the early detection of G6PD deficiency among neonates of the regions mentioned above. We have also investigated the prevalence of the regions and discovered frequency mutations. Those results will help G6PD screening promotion and precision diagnosis for Anhui province.