Determination of optimal cutoff value to accurately identify glucose-6-phosphate dehydrogenase-deficient heterozygous female neonates

• Published in: Clinica chimica acta 2013-09, Vol.424, p.131-135
• Main Authors: Miao, Jing-Kun, Chen, Qi-Xiong, Bao, Li-Ming, Huang, Yi, Zhang, Juan, Wan, Ke-Xing, Yi, Jing, Wang, Shi-Yi, Zou, Lin, Li, Ting-Yu
• Format: Article
• Language: English
• Subjects: China - epidemiology; Cut-off value; Dried Blood Spot Testing; Female; G6PD deficiency; Glucosephosphate Dehydrogenase - blood; Glucosephosphate Dehydrogenase - genetics; Glucosephosphate Dehydrogenase Deficiency - blood; Glucosephosphate Dehydrogenase Deficiency - diagnosis; Glucosephosphate Dehydrogenase Deficiency - epidemiology; Glucosephosphate Dehydrogenase Deficiency - genetics; Heterozygote; Heterozygotes; Humans; Infant, Newborn; Male; Mutation; Neonatal Screening; Newborn screening; Prevalence; ROC Curve
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2013.05.004

Conventional screening tests to assess G6PD deficiency use a low cutoff value of 2.10U/gHb which may not be adequate for detecting females with heterozygous deficiency. The aim of present study was to determine an appropriate cutoff value with increased sensitivity in identifying G6PD-deficient heterozygous females. G6PD activity analysis was performed on 51,747 neonates using semi-quantitative fluorescent spot test. Neonates suspected with G6PD deficiency were further analyzed using quantitatively enzymatic assay and for common G6PD mutations. The cutoff values of G6PD activity were estimated using the receiver operating characteristic curve. Our results demonstrated that using 2.10U/g Hb as a cutoff, the sensitivity of the assay to detect female neonates with G6PD heterozygous deficiency was 83.3%, as compared with 97.6% using 2.55U/g Hb as a cutoff. The high cutoff identified 21% (8/38) of the female neonates with partial G6PD deficiency which were not detected with 2.10U/g Hb. Our study found that high cutoffs, 2.35 and 2.55U/g Hb, would increase assay's sensitivity to identify male and female G6PD deficiency neonates, respectively. We established a reliable cutoff value of G6PD activity with increased sensitivity in identifying female newborns with partial G6PD deficiency. •Semi-quantitative tests with low cut-off value of 2.10U/gHb fail to detect most of the heterozygote females.•We determined an appropriate cut-off value of G6PD activity by combining quantitative enzyme and molecular assay.•We validated this cut-off value of G6PD activity and demonstrated good sensitivity.•They may help enhance the identification of G6PD-deficient heterozygote female newborns.