Glucose-6-phosphate dehydrogenase deficiency neonatal screening: preliminary evidence that a high percentage of partially deficient female neonates are missed during routine screening

Abstract

Objectives-To provide preliminary evidence that the currently employed semiquantitative method of screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency can only detect infants who are totally deficient for G6PD and misses all cases of partial G6PD deficiency. Setting-General population: 2150 randomly selected blood samples from the Blood Donation Department, Speliopouleion General Hospital, Athens, Greece. Neonate population: 2000 samples from neonates (50% male; 50% female) in maternity hospitals in the greater Athens area. High risk population: a total of 545 individuals from 133 families in the Athens area, the minimum acceptance criteria being the parents and any brother or sister. Method-Blood specimens from neonates or adults were collected and either spotted and dried on special filter paper (Schleicher and Schull 2992, Darmstadt, Germany) or used in tubes after being heparinised. For the quantitative evaluation of G6PD enzyme activity, the Quantase G6PD screening kit (Quantase Limited, Perth, UK) was used. Quantase G6PD controls (Quantase Limited) were used at three levels of G6PD. These controls are rated at 24, 30, and 37°C. Alternatively, we used the Sigma G6PDH controls (Sigma Chemical Company, St Louis, USA) which are rated at 30 and 37°C. The assay was performed according to the instructions included in the kit with the modification for haemoglobin normalisation. Results-General population: 36 females who were classified as having normal enzymatic activity with the semiquantitative test, were classified as partially deficient with the quantitative test. Neonate population: using the quantitative test, the percentage of G6PD deficient neonates in this population was 5.5%, compared with 3.17% reported in routine screening using the semiquantitative method. High risk population: the quantitative method detected 28 cases of total or partial G6PD deficiency in sisters of males with known total deficiency. The semiquantitative method only detected 32% (nine out of 28) of these cases.Conclusions-A considerable amount of partially G6PD deficient female neonates (heterozygotes) are undetected and classified as having normal enzymatic activity using the semiquantitative method, which uses a cut oV of 2.1 U/g haemoglobin (Hb). The use of a fully quantitative G6PD screening kit is proposed, employing the automated haemoglobin normalisation and a cut oV of 6.4 U/g Hb. Any neonate with an activity below this mark should be regarded as G6PD deficient, and all preventive measures should be taken. (J Med Screen 2000;7:46-51)

Newborn screening for glucose-6-phosphate dehydrogenase deficiency in Isfahan, Iran: a quantitative assay

“…This study proposed a fully quantitative G6PD screening kit and suggested that any neonate with an activity below 6.4 U/gHb should be considered as G6PD deficient. 12 In the present study, the first report of G6PD deficiency among the all neonates born in Isfahan was made using a fully quantitative method and a cut off of 6.4 U/gHb. In our study, the male to female ratio in G6PD deficient neonates was 5.5:1.…”

Screening and prevention of neonatal glucose 6-phosphate dehydrogenase deficiency in Guangzhou, China

“…This genetic disorder is transmitted from a father to his daughter and from a mother to half of her offspring. Some female heterozygous patients cannot be diagnosed because the G6PD activity value is higher than the cut-off point (Reclos et al, 2000). Lifelong healthcare precautions including regular blood test (for red blood indicators) should be undertaken by patients with G6PD deficiency to prevent hemolysis.…”

Glucose‐6‐phosphate dehydrogenase laboratory assay: How, when, and why?

“…In fact, in steady state conditions, the screening test is low sensitive, because less than 46% of the deficient females results as abnormal at fluorescent semiquantitative biochemical test. Reclos and coworkers (31) reported that up to 60% of heterozygotes were not detected using the spectrophotometric G6PD assay alone.…”

“…This assay discriminates between deficient (partially or totally) and normal case, but presents some disadvantages. The most important drawback of this method is its low cut off limit (\ 2.1 UI/g Hb) that it is too low for an accurate identification of all partially deficient HF (31). In fact it can only recognize the totally deficient individuals (\20% residual enzymatic activity), while it could erroneously classify, as normal, the partially deficient neonates (males and females with residual enzymatic activity between 20 and 60%) (39): because the missed HF might show G6PD-deficient phenotype later, the current G6PD neonatal screening might not be helpful in diagnosis or prevention of this disease in females.…”