Screening of glucose-6-phosphate dehydrogenase deficiency in a cohort of 215,137 newborns: an epidemiological and pathogenic variant spectrum study in Yueyang, China

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is a prevalent inherited metabolic disorder, affecting approximately 500 million individuals worldwide. Current neonatal screening protocols necessitate continuous refinement of cut-off values based on gestational age, birth weight, and seasonal variation. Genetic characterization of G6PD deficiency has become a critical component of newborn screening programs; however, the spectrum of pathogenic variants in the Yueyang region remains elusive.MethodsG6PD enzymatic activity was quantitatively assessed using fluorescence analysis of dried blood spot samples. Infants with abnormal results were recalled for targeted genetic testing focusing on known hotspot mutations.ResultsA total of 215,137 newborns in Yueyang city underwent screening for G6PD deficiency, yielding an estimated overall birth prevalence of 4.77‰. Gestational age showed a consistent, independent negative correlation with G6PD enzymatic activity. The optimal cut-off value for male newborns was adjusted from 2.6 U/g Hb to 3.2 U/g Hb during winter. In total, 336 neonates were confirmed through the genetic diagnosis of G6PD deficiency. The most frequent pathogenic variant was c.1376G>T, accounting for 31.85% of cases, followed by c.1388G>A (22.92%), c.1311C>T (14.88%), c.95A>G (9.82%), c.1024C>T (8.33%), and c.871G>A (6.85%). The c.1376G>T mutation was associated with the greatest reduction in enzymatic activity, with median levels of 0.8 U/g Hb in males and 3.54 U/g Hb in females.ConclusionStratified by gestational age and seasonal variation, cut-off value optimization is essential for ensuring the efficacy of neonatal G6PD deficiency screening. This study primarily focuses on identifying asymptomatic G6PD deficiency and preventing severe hyperbilirubinemia and neurologic damage. Early screening, timely identification, and standardized follow-up should be prioritized to facilitate the implementation of eugenics-related public health strategies.