Detection of Glucose-6-Phosphate Dehydrogenase Deficiency in Heterozygous Saudi Female Neonates

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy affecting 400 million people, globally. G6PD deficiency is an X-linked genetic condition, which is more likely to affect males than females. Heterozygous females go undetected in commonly used method. The aim of the study was to identify & validate female heterozygous neonates, missed in neonatal screening programs. Methods: Blood samples were collected from 984 Saudi neonates (448 Male and 536 Female) in EDTA tubes for quantitative evaluation of G6PD enzyme activity. Quantitative evaluation was done by Sigma diagnostic kits (No. 345-UV). The reduction of nicotinamide adenine dinucleotide phosphate to nicotinamide adenine dinucleotide phosphate oxidase, reflecting G6PD activity was measured spectrophotometrically. Hemoglobin (Hb) was measured on the same sample. G6PD activity was recorded as U/g Hb. Samples identified as deficient with cutoff ≤6.6 U/gHb were subjected to molecular genotyping for common G6PD variants. Results: Out of 448 male neonates, 47 (10.3%) were designated as G6PD deficient with average G6PD enzyme activity of 1.89 U/gHb. Females (536) showed continuum results. With ≤ 4.6 U/gHb cutoff, 14 (2.6%) female neonates were designated as G6PD deficient with average G6PD enzyme activity of 2.6 U/gHb, while with cutoff ≤ 6.6 U/gHb, 34 (6.3%) with average G6PD enzyme activity of 5.5 U/gHb were marked deficit. Additional neonates which were designated as deficit with cutoff ≤ 6.6 U/gHb showed presence of G6PD mutations, 18 (80%) showed G6PD Mediterranean, and 2 (20%) were identified a G6PD Aures. Conclusion: Considerable amounts of partially deficient G6PD female heterozygous are missed, when ≤ 4.6 U/gHb cutoff is used to identify deficient female neonates, however, deficient males, hemizygotes were detected efficiently with ≤ 4.6 U/gHb as cutoff point. Higher reference value (≤ 6.6 U/gHb) is recommended for female neonates.