Department of Pathology and Microbiology, The Aga Khan University Hospital, Karachi, Pakistan.
BMC Pediatr. 2012 Aug 20;12:126. doi: 10.1186/1471-2431-12-126.
There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4-14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T.
This was a case-control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing.
G6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, p < 0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8 ± 5.4 mg/dl vs. 13.8 ± 4.6 mg/dl, p = 0.008) which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, p = 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups.
We concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity.
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症与新生儿高胆红素血症之间存在很强的相关性，这种疾病可能会导致罕见但具有潜在破坏性的急性胆红素脑病。在巴基斯坦，住院的黄疸新生儿中有 4-14%存在 G6PD 缺乏症。在该人群中，最常见的变异是 G6PD c.563C > T。本研究旨在评估携带 G6PD c.563C > T 的婴儿高胆红素血症的发病时间和生后胆红素轨迹。
这是在巴基斯坦 Aga Khan 大学进行的一项病例对照研究，研究时间为 2008 年。我们研究了 216 名在研究期间因光疗而再次住院的男性黄疸新生儿。未进行任何选择。病历显示，32 名婴儿为 G6PD 缺乏症，184 名婴儿为 G6PD 正常。对每个婴儿的出生体重、胎龄、就诊时的年龄、是否存在头颅血肿、败血症和神经系统体征、胆红素峰值、胆红素峰值的年龄、住院天数、是否开始光疗或换血治疗以及结局进行研究。在住院期间，每个婴儿都接受了全血细胞计数、网织红细胞计数、ABO 和 Rh 血型、直接抗球蛋白试验和定量 G6PD 估计[通过 G6PDH 的动力学测定]。通过 PCR-RFLP 分析和基因测序，在 32 名 G6PD 缺乏症婴儿中分析了 G6PD 基因 c.563C > T 和 c.131 C > G 的变异。
在 32 名 G6PD 缺乏症婴儿中，观察到 G6PD 变异 c.563C > T 和 c.131 C > G 分别为 21（65%）和 3（9%）。8（25%）名新生儿的 DNA 特征不明。与 G6PD 正常新生儿相比，携带 c.563C > T 变异的婴儿的酶活性显著降低（均值±1SD；0.3±0.2 U/gHb 比 14.0±4.5 U/gHb，p<0.001），总血清胆红素峰值更高（均值±1SD；16.8±5.4 mg/dl 比 13.8±4.6 mg/dl，p=0.008），且生后更早达到峰值（均值±1SD 2.9±1.6 比 4.3±2.3 天，p=0.007）。两组间的平均体重、就诊年龄、血红蛋白、网织红细胞计数、TSH 水平、住院时间或光疗或换血治疗的起始频率均无统计学差异。
我们得出结论，携带 G6PD c.563C > T 变异的婴儿比 G6PD 酶水平正常的婴儿更早出现黄疸。与 G6PD 正常婴儿相比，携带 G6PD c.563C > T 的婴儿 G6PD 活性显著降低。
