Chinese Newborn Screening for G6PD Deficiency, with Activity and Gene

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene mutation. We aimed to provide the characteristics of G6PD deficiency and G6PD gene mutation distribution in a large Chinese newborn screening (NBS) population. Methods: We collected screening information of all the NBS centers around China, from January 2013 to December 2017. G6PD activity fluorescence screenings and G6PD/6PGD tests were performed in 1,764,299 birth population from 29 centers in 12 representative provinces in 2016. We then performed multicolour melting curve analysis (MMCA) to classify G6PD gene mutations in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site mutations were not found. Finally, we investigated G6PD gene mutation with MMCA in 6,443 female and 7,358 male neonates with normal G6PD activity respectively. Findings: The screened population, organizations and provinces of G6PD deficiency were increased from 2013 to 2017 in China, high in South and low in North. The top 5 frequency of G6PD gene mutations were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and 4 pathogenic mutation sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G ) were firstly reported. Three hundred and seventy-two (372/6,443, 5·77%) female neonates with normal G6PD activity were detected as G6PD gene heterozygotes and 50 (17·42%, 50/287) female G6PD heterozygotes showed G6PD deficiency symptom in two years, suggesting that a supplementary NBS strategy of G6PD gene first screening for female G6PD deficiency in high-incidence regions of South China. Interpretation: G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene mutation varies in different regions and ethnicities. Our suggested NBS strategy for G6PD deficiency could enhance the detection rate of female G6PD heterozygotes. Funding Statement: This work is partially financial supported by Natural Scientific Foundation of China (81570142), and the Ministry of Science and Technology (2016YFA0101300, 2017YFC1001700). Declaration of Interests: All the authors have nothing to disclose. Ethics Approval Statement: This study was approved by the Research Ethics Committees of Children’s Hospital of Chongqing Medical University and registered on Chinese Clinical Trail Registry (ChiCTR-SOC-17014057).