Salicylamide glucuronide formation in newborn babies with G-6-PD deficiency

Salicylamide glucuronide formation has been studied in 23 newborn babies with erythrocyte G-6-PD deficiency and in 15 normal newborns on the first day of life. Glucuronide formation was significantly lower (p less than 0.001) in the former in comparison with the controls. In the newborns with G-6-PD deficiency who subsequently became hyperbilirubinemic an even lower mean glucuronide formation was observed (p less than 0.01) in respect to the non-jaundiced G-6-PD-deficient newborns.     

Neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency in Sephardic-Jewish neonates: incidence, severity, and the effect of phototherapy.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is frequently associated with neonatal hyperbilirubinemia, and sometimes kernicterus, often in the absence of any identifiable trigger or hematological evidence of hemolysis. The aim of this study was to compare the incidence and severity of, and the effect of phototherapy on, jaundice in G 6-PD-deficient vs G-6-PD-normal neonates in the Sephardic-Jewish community. Healthy term newborns, born to mothers of families stemming from geographic areas known to be "at risk" for G-6-PD deficiency, were screened for the condition and surveyed for hyperbilirubinemia. Seventy-five G-6-PD-deficient neonates formed the study group, while 266 neonates with normal levels of the enzyme formed the control group. Neonates with any other identifiable cause for jaundice were excluded. Phototherapy was commenced when the serum bilirubin levels reached 16 mg/dL (274 mumol/L) or more, and it was discontinued at 12 mg/dL (205 mumol/L) or less. Hyperbilirubinemia developed in 27 (36%) of the deficient neonates (serum total bilirubin greater than 13.9 mg/dL [238 mumol/L]), compared with 50 (18.8%) of control neonates (P = .002), while 20 (26.7%) of the study group required phototherapy, compared with 31 (11.7%) of control neonates (P = .002). Two neonates in the study group required exchange transfusion (serum bilirubin greater than 20 mg/dL [342 mumol/L]), vs 0 in the control group (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)     

(TA)n UGT 1A1 promoter polymorphism: a crucial factor in the pathophysiology of jaundice in G-6-PD deficient neonates

Increased heme catabolism has been reported in glucose-6-phosphate dehydrogenase (G-6-PD)-normal neonates who were also homozygous for (TA)7/(TA)7 (UGT1A1*28) uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT) promoter polymorphism (Gilbert syndrome). As G-6-PD deficiency is associated with increased hemolysis, we hypothesized that in G-6-PD-deficient neonates who also have the (TA)7/(TA)7 UGT promoter genotype, steady-state hemolysis would be even further increased. Male G-6-PD-deficient neonates were sampled for plasma total bilirubin (PTB), blood carboxyhemoglobin corrected for inhaled carbon monoxide in ambient air (COHbc) (an index of heme catabolism), and UGT (TA)n promoter genotype determination and compared with previously published G-6-PD-normal neonates. Although COHbc values were higher in the G-6-PD-deficient than in the G-6-PD-normal cohorts (0.97 +/- 0.32% of total Hb (tHb) versus 0.76 +/- 0.19% of tHb, p < 0.001), PTB values were similar (9.2 +/- 3.4 mg/dL versus 8.9 +/- 3.0 mg/dL, respectively, p = 0.3). Within the G-6-PD-deficient group, although COHbc values were alike between the three UGT promoter genotypes, PTB was higher in the (TA)7/(TA)7 homozygotes (11.1 +/- 4.0 mg/dL) compared with (TA)6/(TA)7 heterozygotes (9.1 +/- 3.2 mg/dL, p = 0.03) and wild-type (TA)6/(TA)6 homozygotes (8.8 +/- 3.4 mg/dL, p = 0.02). In the steady state, similar rates of hemolysis, but increased PTB in the G-6-PD- deficient, (TA)7/(TA)7 homozygotes, imply that (TA)7/(TA)7, homozygosity is central to increased PTB.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

Differing pathogenesis of perinatal bilirubinemia in glucose-6-phosphate dehydrogenase-deficient versus-normal neonates

The objective was to compare the contribution to perinatal bilirubinemia of hemolysis and UDP-glucuronosyltransferase (UGT) gene promoter polymorphism, seen in Gilbert's syndrome, between glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and -normal neonates. Serum total bilirubin (STB) values from 52 G-6-PD-deficient and 166 G-6-PD-normal term, male neonates, sampled within 3 h of delivery (first sample) and on d 3 (second sample), were analyzed in relation to blood carboxyhemoglobin corrected for inspired CO (COHbc), an accurate index of hemolysis, and UGT promoter genotype. COHbc values (% total Hb) were greater in G-6-PD-deficient neonates than controls: first sample 1.00 +/- 0.25% versus 0.84 +/- 0.24%, p < 0.0001; second sample 0.83 +/- 0.20% versus 0.76 +/- 0.19%, p = 0.002. First sample COHbc and STB values did not correlate in either the G-6-PD-deficient or control groups, whereas second sample COHbc values correlated significantly with corresponding STB values in the control population only (r = 0.28, p = 0.0007). At second sampling, there was a higher allele frequency of the variant UGT promoter among those with STB values > or =75th percentile than those <75th among the G-6-PD-deficient neonates (0.60 versus 0.33, respectively, p = 0.025), but not controls (0.31 versus 0.40, respectively, p = 0.24). Among those infants with at least one variant UGT promoter allele, STB values were higher in the G-6-PD-deficient neonates than controls at second sampling only (181 +/- 56 microM versus 149 +/- 46 microM, respectively, p = 0.03). Both within and between the G-6-PD-deficient and control groups, our data demonstrate changing and differing contributions of hemolysis and UGT promoter polymorphism to bilirubinemia during the first 3 d of life.     

Neonatal screening for Glucose-6-Phosphate dehydrogenase deficiency

Objective : This study was carried out to detect the incidence of erythrocytic Glucose-6-Phosphate dehydrogenase (G-6-PD) deficiency, to compare the incidence of hyperbilirubinernia in G-6-PD deficient neonates as compared to G-6-PD normal neonates and to asses the usefulness of neonatal screening for G-6-PD deficiency.Method : In a retrospective hospital based study 2,479 male and female neonates consecutively born at Indraprastha Apollo hospital between July 1998 to June 2003 who were screened for G-6-PD levels were evaluated for the incidence of G-6-PD deficiency.Results : Incidence of G-6-PD deficiency was found to be 2.0%. Incidence in males was 283% and femle was 1.05%. The incidence of hyperbilirubinemia was found to be 32% in G-6-PD deficient neonates which was significantly higher than the incidence of hyperbilirubinemia in neonates with normal G-6-PD, which was 12.3% (P<0.001).Conclusion : Our data suggests that neonatal screening for G-6-PD deficiency is a useful test for preventing and early treatment of complications associated with it.     

不同G-6-PD活性新生儿光疗致溶血机制及其预防

目的探讨不同G6PD活性新生儿光疗溶血机制及预防。方法将G6PD正常与缺陷光疗患儿随机分为维生素E干预组和对照组,测定比较超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧(ROS)、总胆红素(TB)、血红蛋白(Hb)及光疗指数。结果光疗前G6PD缺陷组比正常组SOD和Hb低,ROS高;光疗中G6PD缺陷干预组比正常干预组SOD高,MDA低,光疗指数小,G6PD缺陷对照组比正常对照组ROS、MDA高,光疗指数大(各组比较均P<0.01或P<0.05)。光疗后G6PD缺陷对照组Hb下降,并比干预组低,G6PD正常两组Hb均下降,干预组比对照组高(各组比较均P<0.01或P<0.05)。结论光疗可致抗氧化能力下降,脂质过氧化损伤致G6PD缺陷光疗者溶血更突出,维生素E干预更有效。     

血液学参数的变化与红细胞葡萄糖-6-磷酸脱氢酶活性关系的研究

本文报道１６４例住院的高胆红素血症患儿（贫血６６例，无贫血９８例）进行Ｇ－６－ＰＤ活性和几个血液学参数的测定，并作了相关性、回归分析和显著性检验。结果：Ｇ－６－ＰＤ活性与白细胞、网织红细胞、血小板数、血清钠及微量元素锌、硒含量呈正相关；与血红蛋白、红细胞和红细胞压积呈负相关，两者均有显著性意义（Ｐ＜０．０５～０．０１）。而与血清钾、氯、钙、白蛋白、球蛋白及胆红素含量无相关性。通过本实验结果分析，作者认为高胆红素血症患儿，伴有贫血或溶血时，由于骨髓增生，网织红细胞和年幼的红细胞数量增加，或者伴随感染时因白细胞明显增加等因素，致Ｇ－６－ＰＤ活性含量升高而掩盖了Ｇ－６－ＰＤ缺陷。因此，评价Ｇ－６－ＰＤ活性时，除了考虑以上几个血液学参数影响造成的误差，对贫血患儿的血样常规先行调整血浆和血细胞的比例外，白细胞增加者若能进行离心除去白细胞层后进行测定；或待感染控制后，有贫血者待贫血改善后；有溶血者待溶血停止后２—４个月左右，再复查Ｇ－６－ＰＤ活性，对Ｇ－６－ＰＤ缺陷才能作出正确的诊断。     

遗传因素在广西新生儿高胆红素血症中的作用

目的探讨UGT1A1 G71R突变、OATP2A388G突变和G-6-PD缺乏对在广西新生儿高胆红素血症发病的作用。方法用四氮唑蓝定量法（NBT法）测定G-6-PD酶活性。聚合酶链反应-等位基因特异性寡核苷酸探针点杂交（PCR-ASO）法确定G71R基因型。限制性片段长度多态性分析（RFLP）检测A388G基因型。测定109例新生儿脐血的G-6-PD活性及G71R基因型,其中101例同时检测了A388G基因型。据G-6-PD活性及G71R或A388G基因型分组,分析UGT1A1G71R突变、OATP2A388G突变和G-6-PD缺乏与足月新生儿高胆红素血症之间关系。结果G71R等位基因频率在G-6-PD缺乏组为22．03％,在G-6-PD正常组为28．00％。G-6-PD缺乏共存有G71R突变纯合子或杂合子的新生儿高胆红素血症发生率（95．50％）高于G-6-PD正常且G71R为野生型的新生儿（53．90％）,x^2=10．45,P=0．0012,前者发生高胆红素血症的机会比（95％可信区间）[OR（95％CI）]为18．00（2．12,152．9）。A388G等位基因频率在G-6-PD缺乏组为20．O％,在G-6-PD正常组为18．5％。G-6-PD缺乏共存有A388G突变新生儿的高胆红素血症发生率（90．0％）高于G-6-PD正常且A388G为野生型的新生）L（44．80％）,X2=10．39,P=0．0013,前者发生高胆红素血症的伽（95％CT）为11．08（2．15,56．48）。结论G71R突变与G-6-PD缺乏共存或A388G突变与G-6-PD缺乏共存对广西足月新生儿高胆红素血症的发生有协同作用。     

Neonatal hyperbilirubinemia in African American males: the importance of glucose-6-phosphate dehydrogenase deficiency

OBJECTIVE: To perform risk factor analysis for the prediction of hyperbilirubinemia in an African American male neonatal cohort. STUDY DESIGN: A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for hyperbilirubinemia. Factors studied included birth weight >/=4.0 kg, gestational age /=75(th) percentile. Hyperbilirubinemia was defined as any bilirubin value >/=95(th) percentile on the hour-of-life-specific bilirubin nomogram. RESULTS: Forty-three (8.6%) neonates developed hyperbilirubinemia. At 48 +/- 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75(th) percentile 10.0 mg/dL, and 95(th) percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin >/=75(th) percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P < .0001, respectively). G-6-PD-deficient neonates who were also premature and breast-feeding had the highest incidence of hyperbilirubinemia (60%). CONCLUSIONS: African American male neonates may be at higher risk for hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in hyperbilirubinemia prediction in these newborns.     

Cord plasma alpha-fetoprotein values and neonatal jaundice

Umbilical cord plasma alpha-fetoprotein (AFP) values were determined in 127 infants with hyperbilirubinemia (56 glucose-6-phosphate dehydrogenase (G-6-PD) deficient and 71 G-6-PD normal) and 136 control subjects (73 G-6-PD deficient and 63 G-6-PD normal). The mean alpha-fetoprotein value of 173 +/- 35.2 (SD) mg/L for the group of infants with hyperbilirubinemia was significantly greater than that (122 +/- 21.7 mg/L) for the control infants (P less than .001). G-6-PD status and sex did not significantly affect the alpha-fetoprotein values. Using an alpha-fetoprotein level of 130 mg/L as a "cut-off" value, the incidence of false-positive results was 25.5% and the incidence of false-negative results was 11.8%. This test can be used as a screening procedure to detect infants at high risk for hyperbilirubinemia.     

葡萄糖-6-磷酸脱氢酶缺乏症患儿G-6-PDmRNA表达的研究

目的：检测葡萄糖-6-磷酸脱氢酶(G-6-PD)缺乏症患者及其家系成员的G-6-PDmRNA表达水平,从转录水平探讨其可能的发病机制。方法：提取G-6-PD缺乏症患者及其直系家属(患者父亲和/或母亲等)外周血RNA,采用逆转录方法形成cDNA后,运用逆转录实时定量PCR(QuantitativeReal-TimePCR,QRT-PCR)技术,测定G-6-PDmRNA的表达量。使用SPSS10.0统计分析软件将3组进行组间两两比较。结果：G-6-PD缺乏症患儿组mRNA表达量为0.57±0.19,父系组为0.74±0.21,母系组为0.67±0.21,患儿组与父系组比较t=-3.18,(P<0.01);与母系组比较t=-2.54,(P<0.05)。结论：G-6-PD缺乏症患者的G-6-PD基因发生突变后其G-6-PDmRNA表达量发生了改变,提示该病的发生与在转录水平上发生变化有关,在G-6-PD缺乏症的发病过程中起到一定的作用。     

Glucose-6-phosphate dehydrogenase,reduced glutathione and heinz bodies in congenital haemolytic anaemia

Summary Glucose-6-phosphate dehydrogenase (G-6-PD), glutathione instability (GSH) and heinz body formation were studied in ten children suffering from congenital haemolytic anaemia and in fifteen healthy subjects of similar age group. In congenital haemolytic anaemia, dye decolorisation time for assessing G-6-PD activity was within the normal range. Unstable GSH was less than 20% in four cases and more than 20% in the other four cases. In two cases no unstable GSH was observed. Heinz bodies, more than 50%, were present in nine of ten cases. Glutathione instability and increased percentage of heinz body formation with normal G-6-PD activity probably occurs due to glutathione reductase or TPNH (NADPH) deficiency. From the Department of Pathology and Microbiology, Sandar Patel Medical College, Bikaner, Rajasthan.     

广西南宁地区G6PD基因突变与新生儿黄疸的关系

目的：分析本地区最常见的三种基因突变型G1388A、G1376T和A95G与葡萄糖-6-磷酸脱氢酶（G-6-PD）活性之间的相关性,并探讨G-6-PD基因突变对新生儿黄疸的影响。方法：124例广西南宁的高胆红素血症新生儿为研究对象。应用突变特异性扩增系统法检测G-6-PD基因突变,应用硝基四氮唑蓝（NBT）定量法检测G-6-PD活性。比较G-6-PD不同基因突变型之间以及与正常组之间胆红素脑病发生率、出生72 h后血清胆红素峰值组间的差异。采用非条件logistic回归分析血清胆红素值>340 μmol/L的危险度。结果：124例中有37例G-6-PD 基因突变（G1388A 20例,G1376T 14例,A95G 4例,1例同时存在G1388A与A95G突变）。20例G1388A突变者中5例（25%）G-6-PD酶活性正常,14例G1376T突变者中4例（29%）G-6-PD酶活性正常,4例A95G突变者G-6-PD 酶活性均缺乏。G1388A与G1376T组胆红素脑病发生率及出生72 h后血清胆红素峰值差异无显著性。G-6-PD 突变组出生72 h后血清胆红素峰值、胆红素脑病发生率及血清胆红素>340 μmol/L的危险度与G-6-PD正常组相比,差异无显著性。结论：广西南宁地区G-6-PD突变仍常见G1388A、G1376T和A95G基因型。NBT法诊断G-6-PD缺乏存在假阴性。不同基因型对出生72 h后血清胆红素峰值、胆红素脑病发生率的影响无差异。单独的G-6-PD基因突变对生后72 h血清胆红素峰值、急性胆红素脑病发生率及血清胆红素大于340 μmol/L危险性均无影响。［中国当代儿科杂志,2009,11（12）：970-972］     

运用PCR-DGGE技术检测葡萄糖-6-磷酸脱氢酶缺乏的初步研究

目的：运用多聚酶链反应-变性梯度凝胶电泳（PCR-DGGE）技术检测葡萄糖-6-磷酸脱氢酶（G-6-PD）缺乏患者及基因携带者基因变异,探讨其对该病的诊断和研究价值。方法：提取G-6-PD缺乏症患者及其家系（患者父亲和/或母亲等）的外周血RNA,逆转录合成cDNA后,选取第11至12外显子部分cDNA片段进行PCR-DGGE,观察其电泳行为,将电泳行为异常的标本进行基因测序,最后做出基因诊断。结果:：36个家系中33个家系发现G-6-PD基因在1304至1520片段出现PCR-DGGE多种异常电泳区带。9例母亲G-6-PD/6-PGD比值低于1.00,其中3例比值低于0.50,而且PCR-DGGE电泳行为一致,基因测序发现为双重杂合子;比值正常的G-6-PD缺乏基因携带者母亲均为单杂合子。该片段基因测序发现3个突变位点分别为：C1311T,G1376T,G1388A。各基因突变的位点有其特殊的电泳行为。结论：PCR-DGGE技术是一种敏感性高、可靠性强的筛查基因突变的方法。在临床研究G-6-PD缺乏,特别是常规诊断技术不能发现的女性G-6-PD缺乏基因携带者的检测中具有很强的应用价值。［中国当代儿科杂志,2007,9（6）：529-532］     

Agar in control of hyperbilirubinemia of full-term newborn infants with erythrocyte G-6-PD deficiency.

40 full-term newborn infants with erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were used for a study concerning the effectiveness of agar per os in preventing severe hyperbilirubinemia. 20 randomly selected neonates were given agar (1 g/kg/day) orally in 4 daily doses from their 1st to their 5th day of life. 20 infants were not treated and served as controls. Three exchange transfusions were performed in the experimental as well as in the control group. According to these results, agar does not seem to be effective in preventing severe hyperbilirubinemia, which frequently occurs in newborn infants with erythrocyte G-6-PD deficiency.     

EFFECT OF OROTIC ACID UPON SERUM BILIRUBIN IN NEWBORN INFANTS WITH ERYTHROCYTE G-6-PD DEFICIENCY

Fifty mature male newborns with erythrocyte G-6-PD deficiency were used for a study con cerning the effectiveness of orotic acid in preventing severe hyperbilirubinemia. Twentyfive randomly selected neonates were given orotic acid (100 mg/kg/day) orally in two daily doses from their 1st to their 5th day of life. Twenty-five newborns were not treated According to these results orotic acid does not seem to be effective in preventing severe hyperbilirubinemia, which frequently occurs in newborn babies' with erythrocyte G-6-PD deficiency. and served as controls. Six exchange transfusions were performed in the test group and six in the controls.     

Phototherapy for neonatal hyperbilirubinemia in mature newborn infants with erythrocyte G-6-PD deficiency

Phototherapy was employed in treatment of newborn infants with erythrocyte G-6-PD deficiency whose serum bilirubin concentrations exceeded 10 mg/100 ml on the second or third day of life. Exchange transfusions were required for two of the 12 treated babies and for six of the 12 control infants. It is noteworthy that exposure to light did not affect the erythrocyte GSH content nor did it increase hemolysis.     

Red cell metabolic alterations in postnatal life in term infants: glycolytic enzymes and glucose-6-phosphate dehydrogenase

The activities of red cell enzymes enolase (ENO), phosphoglycerate kinase (PGK), phosphofructokinase (PFK), glucose-6-phosphate dehydrogenase (G-6-PD), hexokinase (HK), aldolase (ALD), and pyruvate kinase (PK) were followed sequentially in term infants from birth to one year of age. At birth, red cell PGK and ENO activities were disproportionately elevated when compared to both red cells with a similar mean cell age and those with a younger mean cell age; red cell PFK was significantly decreased. There was a progressive full in PGK and ENO activities and rise in PFK levels toward normal values in the first year of life. The most significant changes in PGK, ENO, and PFK appeared to begin at 8 to 9 wk of age. ENO and PFK activities stabilized at approximately 5 to 6 months of age at values compatible with mean cell age; mean PGK levels remained mildly elevated at 11 to 12 months. The age-dependent enzymes G-6-PD, PK, ALD, and HK were all elevated in term newborns. G-6-PD and ALD progressively decreased in activity during the first year of life. PK and HK decreased in activity until 8 to 9 wk when there was a secondary rise in mean activity. Mean red cell G-6-PD, PK, ALD, and HK levels remained mildly to moderately elevated at 11 to 12 months of life, suggesting the persistence of a relatively young red cell population throughout the first year of life.     

Glucose-6-Phosphate Dehydrogenase Deficiency in Female Heterozygoses and the X-Inactivation Hypothesis

The levels of G-6-PD activity in 75 female heterozygotes detected by pedigree analysis are reported, together with biochemical and genetic data of a pedigree in which a wide variation in G-6-PD activity was revealed in heterozygotes. The results strongly favour the hypothesis that one X-chromosome is inactivated during early embryonic development in the human female, at least as far as the locus of G-6-PD is concerned.