To explore the glucose-6-phosphate dehydrogenase (G6PD) and its gene mutation in G6PD deficiency neonates, and to provide reference for clinical diagnosis of G6PD deficiency infants.

A total of 105 766 newborns screened at Neonatal Screening Center of Shanghai Children′s Hospital from August 2017 to April 2019 were collected. A total of 217 children were initially screened positive for G6PD deficiency, including 161 neonates who were recalled for re-screening for G6PD and/or G6PD gene mutations. And these 161 neonates were selected as research subjects. All of them received re-screening for G6PD, and 146 cases received G6PD gene mutation detection.The male children and their mothers, female children and their parents (the male children′s mothers and female children′s parents were collectively referred as family members of children) received quantitative analysis of G6PD enzyme activity and detection of G6PD gene mutation in children and their family members at the same time. The G6PD enzyme activity, G6PD gene mutation site and its regional distribution characteristics in children and their family members, and the relationship between G6PD enzyme activity and different G6PD gene mutation sites were analyzed. Mann-Whitney U test and Kruskal-Wallis H rank sum test were used for comparisons of G6PD enzyme activity between children and their family members, and relation between G6PD enzyme activity and different sites of G6PD gene mutation. The study was in accordance with the requirements of World Medical Association Helsinki Declaration revised in 2013, and informed consent for clinical research was signed with the children′s guardians.

①Based on results of combined laboratory diagnosis and/or genetic diagnosis, 124 newborns with G6PD deficiency were finally diagnosed (121 cases were diagnosed by G6PD enzyme activity test, 113 cases were diagnosed by G6PD gene mutation detection, and 110 cases were diagnosed by these two methods). ②Among the 121 children diagnosed as G6PD deficiency by G6PD enzyme activity test, 103 were male and 18 were female.G6PD enzyme activity of the 121 children was 0.42 U/g hemoglobin (Hb) (0.35-0.67 U/g Hb), which was significantly lower than 1.17 U/g Hb (0.91-1.42 U/g Hb) of their family members. G6PD enzyme activity of male children was 0.40 U/g Hb (0.32-0.53 U/g Hb), which was significantly lower than 1.12 U/g Hb (0.91-1.28 U/g Hb) of their mothers. G6PD enzyme activity in female children was 1.16 U/g Hb (0.92-1.46 U/g Hb), which was significantly lower than 1.74 U/g Hb (0.69-2.80 U/g Hb) of their parents.All the above differences were statistically significant (Z=-9.981, -10.832, -2.021; P<0.001, <0.001, =0.043). ③Among 161 neonates, 146 cases of children and 185 cases of their family members were tested for G6PD gene mutation, and 227 of them (113 children and 114 family members) carried G6PD gene mutation, among which 3 were complex mutations.A total of 230 G6PD gene mutation sites were detected, and the top four were 1376G>T, 1388G>A, 95A>G, and 1024C>T, accounting for 77.8% (179/230). For 227 cases of G6PD gene mutation carriers, 43, 39, 35, 34, 30 and 46 cases were found to be from Fujian Province, Guangxi Zhuang Autonomous Region, Guangdong Province, Jiangxi Province, Sichuan Province and other regions, respectively, the top two G6PD gene mutation sites in the above regions were 1376G>T and 1388G>A, 1388G>A and 1376G>T, 871G>A and 1024C>T, 1388G>A and 871G>A, 1024C>T and 1376G>T, 1376G>T and 1388G>A, respectively. ④There was no significant difference in G6PD enzyme activity among children and their family members with top four G6PD gene mutation sites 1376G>T, 1388G>A, 95A>G and 1024C>T (χ²=7.642, P=0.061).

G6PD enzyme activity testland G6PD gene mutation detection have diagnostic significance for children with G6PD deficiency. G6PD gene mutation site has the characteristics of regional distribution in children with G6PD deficiency and their family members. There is no significant relationship between G6PD gene mutation site and G6PD enzyme activity, so the G6PD enzyme activity of children with G6PD deficiency could not be predicted by G6PD gene mutation site.