Riskin Arieh, Bravdo Yulia, Habib Clair, Maor Irit, Mousa Julnar, Shahbarat Sizett, Shahak Elena, Shalata Adel
Department of Neonatology, Bnai Zion Medical Center, Ruth & Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa 32000, Israel.
Department of Pediatrics, Bnai Zion Medical Center, Ruth & Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa 32000, Israel.
Children (Basel). 2023 Jul 6;10(7):1172. doi: 10.3390/children10071172.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency and polymorphism in uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) were associated with significant neonatal hyperbilirubinemia (NHB) and increased risk for kernicterus. However, quantitative screening tests for G6PD enzyme activity proved unsatisfactory in estimating the risk for significant NHB, especially in heterozygous females that could present phenotype overlap between normal homozygotes, heterozygotes, and deficient homozygotes, resulting in a continuum of intermediate G6PD activity.
To examine the association of genotype and phenotype in newborns with decreased G6PD activity and its relation to NHB.
Quantitative G6PD enzyme activities were measured on umbilical cord blood samples. After accepting parental consent, samples were analyzed for mutations and gene polymorphisms (number of TA repeats in the UGT1A1 promoter). The associations to quantitative G6PD activity and bilirubin levels were assessed.
28 females and 27 males were studied. The mutation () was responsible for most cases of G6PD deficiency (20 hemizygous males, 3 homozygous and 16 heterozygous females). The association between this mutation, decreased G6PD activity and higher bilirubin levels was confirmed. Heterozygosity to 6/7 TA repeats in the promoter was associated with increased NHB, especially in female newborns with G6PD deficiency. However, it seems that the interaction between G6PD deficiency, promoter polymorphism, and NHB is more complex, possibly involving other genetic interactions, not yet described. Despite genotyping females with G6PD deficiency, the overlap between the upper range of borderline and the lower range of normal G6PD activity could not be resolved.
The results of this study highlight the possibility for future implementation of molecular genetic screening to identify infants at risk for significant NHB, especially polymorphism in heterozygous females with borderline G6PD deficiency. However, further studies are needed before such screening could be applicable to daily practice.
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症以及尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1）的多态性与显著的新生儿高胆红素血症（NHB）以及核黄疸风险增加相关。然而，G6PD酶活性的定量筛查试验在评估显著NHB风险方面并不令人满意，尤其是在杂合子女性中，她们可能表现出正常纯合子、杂合子和缺陷纯合子之间的表型重叠，导致G6PD活性呈现连续的中间值。
研究G6PD活性降低的新生儿的基因型与表型之间的关联及其与NHB的关系。
对脐带血样本进行G6PD酶活性定量测定。在获得家长同意后，对样本进行突变和基因多态性分析（UGT1A1启动子中TA重复序列的数量）。评估其与G6PD活性定量和胆红素水平的关联。
共研究了28名女性和27名男性。G6PD缺乏症的大多数病例由突变（）引起（20名半合子男性、3名纯合子和16名杂合子女性）。该突变、G6PD活性降低与较高胆红素水平之间的关联得到证实。UGT1A1启动子中6/7 TA重复序列的杂合性与NHB增加相关，尤其是在患有G6PD缺乏症的女性新生儿中。然而，G6PD缺乏症、UGT1A1启动子多态性与NHB之间的相互作用似乎更为复杂，可能涉及尚未描述的其他基因相互作用。尽管对患有G6PD缺乏症的女性进行了基因分型，但临界值上限与正常G6PD活性下限之间的重叠仍无法解决。
本研究结果凸显了未来实施分子遗传筛查以识别有显著NHB风险婴儿的可能性，尤其是在G6PD缺乏临界值的杂合子女性中的UGT1A1多态性。然而，在这种筛查适用于日常实践之前，还需要进一步研究。
