Haemolytic Crises due to Glucose-6-Phosphate Dehydrogenase Deficiency in the Mid-Southern Region of Turkey

ABSTRACT. Clinical and laboratory evaluation of 60 boys with hemizygous, 12 girls with homozygous, and 11 girls with heterozygous erythrocyte glucose-6-phosphate dehydrogenase deficiency was made during haemolytic crisis. The main clinical symptoms were paleness, dark urine and oliguria. Only one patient needed peritoneal dialysis. Coexistence of glucose-6-phosphate dehyrogenase deficiency associated with haemoglobinopathy was found to be higher than expected (32 out of 83 cases). Also, the high prevalence of glucose-6-phosphate dehydrogenase deficiency among females with homozygous and heterozygous disease was surprising. The precipitating factors of haemolysis were variable. Rather than antimalarial and antipyretic-analgesic drugs, infections seemed to be the main haemolytic factor.     

THE RISK OF JAUNDICE IN GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENT BABIES EXPOSED TO MENTHOL

Abstract. Olowe, S. A. and Ransome-Kuti, O. (Department of Paediatrics, College of Medicine of the University of Lagos, Lagos, Nigeria). The risk of jaundice in glucose-6-phosphate dehydrogenase babies exposed to menthol. Acta Paediatr Scand, 69:341, 1980.—A major cause of neonatal morbidity and mortality in Lagos, Nigeria, is severe neonatal jaundice seen in G-6-PD deficient babies. The observation that the jaundice is more severe in outpatient than in inpatient babies suggests that its cause is exogenous. "Mentholated" powder which is commonly used in many clinics and at home to dress umbilical cords was suspected to be the offending agent. A controlled study of the effects of one of these powders was carried out on 60 consecutive G-6-PD deficient babies. In 30 of them the umbilical cords were dressed daily with the powder while the remaining half who were untreated served as controls. The treated babies developed statistically more significant jaundice than the controls. Inability of neonates to conjugate menthol in this power is probably responsible for the jaundice developed by these G-6-PD deficient babies. It is concluded that the use of menthol and/or camphor-containing commercial products on neonates be discontinued, especially in communities where the incidence of G-6-PD deficiency is high as the use of such products may be contributing to the severity of neonatal jaundice.     

PCR-Based Allelic Discrimination for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency in Ugandan Umbilical Cord Blood

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked disorder in the world. G6PD deficiency puts children at risk for hyperbilirubinemia and kernicterus during the newborn period and an increased risk of severe hemolysis after exposure to many antimalarial medications. A laboratory diagnosis of G6PD deficiency is rare in the developing world due to limited resources. We developed a TaqMan-based allele-specific assay to rapidly determine rates of G6PD deficiency contributing alleles (G202A and A376G) in East Africa. We tested umbilical cord blood from 100 Ugandan newborns and found that the overall allele frequency of G202A was .13 and A376G was .32. The overall incidence of G6PD A? (G202A/A376G) was 6%; all A? variants were males. There was no correlation between G6PD deficiency and umbilical cord blood hemoglobin, white blood count, platelet count, or other hematologic parameters. Allele-specific PCR can serve as a rapid method to determine specific G6PD deficiency allele frequencies in a given population and as a diagnostic tool in a hospital setting in which laboratory resources are present.     

广西地区葡萄糖-6-磷酸脱氢酶缺乏症与病毒性肝炎的关系

目的了解病毒性肝炎并葡萄糖-6磷-酸脱氢酶(G6PD)缺乏症患儿的基因突变类型,探讨G6PD缺乏基因突变与病毒性肝炎的关系。方法采用自然或错配引物介导的聚合酶链反应(PCR)限/制性内切酶分析,对病毒性肝炎并G6PD缺乏症18例患儿进行G6PD基因3种常见突变类型的分析,并对其临床表现进行分析。结果18例检测出8例G1388A突变,4例G1376T突变,1例A95G突变,突变率为72.22%,与单纯的G6PD缺乏症的基因突变型比较无显著差异。肝炎并G6PD缺乏症患儿急性溶血及急性肾衰竭的发生较单纯肝炎明显增加。结论肝炎患儿G6PD缺乏可能是原发性改变,而肝炎并G6PD缺乏症患儿较单纯肝炎病情重、并发症多。     

广西恭城县瑶族和汉族居民G-6-PD缺乏症发病率及基因频率的调查

目的研究广西恭城县瑶族和汉族居民的G-6-PD缺乏症发病率及基因频率。方法使用G-6-PD试纸法初筛，四氮唑蓝定量法测定确认的方法调查对2050名（男1126，女1124）瑶族和874名（男481，女393）汉族初中学生进行G-6-PD缺乏症的调查。结果瑶族男缺乏率5．75％（显著缺乏4．87％，中度缺乏0．97％），瑶族女性缺乏率1．95％（显著0．59％，中度1．36％）。瑶族男女合并总缺乏率为3．85％；瑶族男性基因频率为：0．057，瑶族女性杂合子的估计值为10．84％：汉族男性缺乏率7.06％（显著缺乏6．03％，中度缺乏1．04％），汉族女性缺乏率3．56％（显著0．76％，中度2.80％），汉族男女合并总缺乏率为5．49％；汉族男性基因频率为0．0706，汉族女性杂合子的估计值为13．12％；全县瑶族和汉族合并缺乏率为4．34％。结论恭城县G-6-PD缺乏发病率，瑶族比汉族的稍低，但民族间的差异比地域间的差异相对要小。     

广西恭城县瑶族和汉族居民G-6-PD缺乏症发病率及基因频率的调查

目的研究广西恭城县瑶族和汉族居民的G-6-PD缺乏症发病率及基因频率。方法使用G-6-PD试纸法初筛,四氮唑蓝定量法测定确认的方法调查对2050名(男1126,女1124)瑶族和874名(男481,女393)汉族初中学生进行G-6-PD缺乏症的调查。结果瑶族男缺乏率5·75%(显著缺乏4·87%,中度缺乏0·97%),瑶族女性缺乏率1.95%(显著0·59%,中度1·36%),瑶族男女合并总缺乏率为3·85%;瑶族男性基因频率为:0·057,瑶族女性杂合子的估计值为10·84%:汉族男性缺乏率7·06%(显著缺乏6·03%,中度缺乏1·04%),汉族女性缺乏率3·56%(显著0·76%,中度2·80%),汉族男女合并总缺乏率为5·49%;汉族男性基因频率为0·0706,汉族女性杂合子的估计值为13·12%;全县瑶族和汉族合并缺乏率为4·34%。结论恭城县G-6-PD缺乏发病率,瑶族比汉族的稍低,但民族间的差异比地域间的差异相对要小。     

Preliminary Report on Neonatal Screening for Congenital Hypothyroidism,Congenital Adrenal Hyperplasia and Glucose-6-Phosphate Dehydrogenase Deficiency: A Chandigarh Experience

Objective  

To establish newborn screening in Indian scenario that could lay a framework for future such initiatives. Three disorders namely, congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and glucose-6-phosphate dehydrogenase deficiency (G-6-PDD) were selected for a preliminary study for newborn screening.     

Poor correlation between hemolysis and jaundice in glucose 6-phosphate dehydrogenase-deficient babies

BACKGROUND: The role of hemolysis in the pathophysiology of neonatal jaundice (NNJ) in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency has been questioned recently. The aim of the present study was to determine the contribution of hemolysis to the pathophysiology of jaundice in Malay neonates with G6PD deficiency and NNJ. METHODS: Four groups of babies were included in the study: (i) G6PD deficient with NNJ; (ii) G6PD deficient without NNJ; (iii) G6PD normal with NNJ; and (iv) normal controls. Babies with other known causes of jaundice were excluded from the study. All subjects underwent the following investigations on day 3-5 after birth: hemoglobin level (Hb), serum bilirubin level, carboxyhemoglobin (CO-Hb) concentration, reticulocyte count and full blood picture. The results of the investigations were compared between the groups using SPSS version 11. RESULTS: Babies with G6PD and jaundice had a similar percentage of CO-Hb to babies with G6PD without NNJ or babies with normal G6PD and NNJ (1.76 +/- 0.40% vs 1.66 +/- 0.31% and 1.67 +/- 0.28%, respectively; P: 0.23 and 0.41, respectively). Total Hb levels and reticulocyte counts were not significantly different between the groups. The blood film showed more (even though not reaching significance) hemolysis in the G6PD patients but results of the blood film were very similar for G6PD patients with and those without NNJ. CONCLUSION: Hemolysis is not a main determinant of neonatal jaundice in G6PD-deficient babies.     

The Effects of Neonatal Jaundice and Respiratory Complications on Learning and Habituation in 5- to 11-month-old Infants

The influences of neonatal hyperbilirubinemia and respiratory complications were examined in 5- to 11-month-old infants in two studies. One study focused on habituation performance and the other on contingency learning. In both experiments, three neonatal jaundice conditions (no jaundice history, measured bilirubin, phototherapy) were crossed with two levels of neonatal respiratory risk (no oxygen intervention, oxygen intervention). For low respiratory risk subjects there were increasingly adverse effects for both habituation and learning the more severe the jaundice history. A complex pattern emerged for the high respiratory risk groups. Only for the learning task were the results consistent with a summative effect of neonatal jaundice and respiratory risk factors.     

广西柳州地区G-6PD基因突变与新生儿黄疸关系的初步探讨

目的　了解广西柳州地区葡萄糖 6磷酸脱氢酶 (G 6PD)缺陷症的基因突变类型。探讨G 6PD缺陷基因突变与新生儿疸的关系。方法　采用基因芯片技术 ,对 4 4例广西柳州地区籍因新生儿黄疸住院的G 6PD缺陷儿进行检测 ,并对其临床表现进行分析。结果　 4 4例 (5 1条X染色体 )患儿中检出G1388A 2 0例 (2 2 / 5 1,基因发生频率 4 3 1% ) ,G1376T 9例 (11/ 5 1,2 1 6 % ) ,A95G 6例 (8/ 5 1,15 7% ) ,G392T 5例 (6 / 5 1,11 8% ) ,C10 2 4T 1例 (1/ 5 1,2 0 % ) ,未定型 3例。G1388A基因型患儿黄疸持续时间与G392T基因型比较差异有显著性(P <0 0 1) ;G1388A基因型的血红蛋白分别与G1376A、A95G的血红蛋白比较差异有显著性 (均P <0 0 5 ) ;各基因型患儿黄疸出现时间、血总胆红素值及间接胆红素值比较差异均无显著性 (P >0 0 5 )。结论　G1388A、G1376T、A95G突变型是广西柳州地区最常见的G 6PD突变型。G1388A基因型患儿黄疸持续时间较长、黄疸程度及贫血程度比较重 ;1388位的突变可能与重型新生儿黄疸相关。     

Neonatal cholestasis and glucose‐6‐P‐dehydrogenase deficiency

We report a Caucasian neonate with chronic non‐spherocytic hemolytic anemia due to a class I G6PD deficiency. A novel mutation missense mutation in exon eight of the G6PD gene was detected (c.827C>T p.Pro276Leu). Bilirubin peaked on day 5 at 24 mg/dl with a conjugated bilirubin of 17 mg/dl. Jaundice resolved within 4 weeks. A detailed work‐up failed to reveal other specific factors contributing to cholestasis. Severe hemolytic disease of the newborn may cause cholestasis even in the absence of associated primary hepato‐biliary disease. Pediatr Blood Cancer 2010;54:758–760. © 2010 Wiley‐Liss, Inc.     

The Relationship between Decreased Iron Stores, Serum Iron and Neonatal Hypoglycemia in Large-for-Date Newborn Infants

ABSTRACT. We assessed the relationship between neonatal hypoglycemia and newborn iron status in 15 hypoglycemic, large-for-date newborn infants, 12 of whom were infants of diabetic mothers. These infants had significantly lower mean serum iron concentrations, ferritin concentrations, percent iron-binding saturation and calculated iron stores, and significantly higher mean transferrin concentrations, total iron-binding capacity concentrations and mid-arm circumference: head circumference ratios when compared with either 15 euglycemic large-for-date or 15 euglycemic appropriate-for-date control infants ( p < 0.001 for all comparisons). All hypoglycemic infants had ferritin concentrations below the 5th percentile as compared to 3 % of controls ( p < 0.001), and 67 % had transferrin concentrations above the 95th percentile (controls: 0 %; p < 0.001). Only the hypoglycemic infants demonstrated a significant negative linear correlation between ferritin and transferrin concentrations ( r =−0.83; p < 0.001). Decreased serum iron concentrations were associated with size at birth ( r =−0.60; p = 0.01) and with increased red cell iron ( r =−0.60; p = 0.01), implying a redistribution of iron dependent on the degree of fetal hyperglycemia and hyperinsulinemia. Infants with increased red cell iron had more profound neonatal hypoglycemia. These results show a significant association between decreased iron stores and neonatal hypoglycemia in macrosomic newborn infants associated with a significant shift of iron into red blood cells.     

Association Between G6PD Deficiency and Hyperbilirubinemia in Neonates: A Meta-Analysis

Hyperbilirubinemia is prevalent in newborns and multiple factors are responsible for the occurrence of neonatal hyperbilirubinemia. G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency is recognized as one of the risk factors. However, many pediatricians did not take into account the probable effect of G6PD-deficiency when severe neonatal hyperbilirubinemia occurred. The aim of the present study was to perform a meta-analysis to investigate whether G6PD-deficiency increases the risk of hyperbilirubinemia and phototherapy in newborn. We searched PubMed and Embase databases for eligible articles according to explicit study inclusion and exclusion criteria. Risk ratios (RRs) and 95% confidence interval (CI) were selected as the evaluation indexes. Cochrane Q and I² test were utilized to assess the heterogeneity among studies. A total of five cohort studies were included in this meta-analysis. There were 21,585 participants enrolled in these studies including 877 newborns with hyperbilirubinemia and 261 newborns receiving phototherapy. Comparison of the incidence of hyperbilirubinemia in newborns with G6PD-deficiency to the ones with normal G6PD in each study yielded a pooled RR of 3.92 (95% CI, 2.13–7.20; P <.0001). The pooled RR of receiving phototherapy in G6PD-deficiency neonates is 3.01 (95% CI, 2.20–4.12; P <.0001) when compared to G6PD normal neonates. This study revealed a significant correlation between G6PD-deficiency and neonatal hyperbilirubinemia, as well as G6PD-deficiency and phototherapy. G6PD-deficient newborns have higher risk of hyperbilirubinemia and phototherapy than the ones with normal G6PD. Monitoring the level of G6PD in newborns is important for predicting the occurrence of hyperbilirubinemia.     

Neonatal jaundice: Its prevalance in Chinese babies and associating factors

A prospective study of 1238 full-term Chinese newborn infants was conducted to determine the incidence of neonatal jaundice and associated factors. A significantly more severe degree of hyperbilirubinaemia was present in infants whose ABO blood group was incompatible with that of their mothers and those who were deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Among the remainder, clinical jaundice was present in 87% and 23.9% had a peak serum bilirubin (SB) concentration greater than 204 mol/l. Factors that were found to have an association with a higher peak SB concentration included: male infants; elder siblings who had a history of neonatal jaundice; and breast-fed infants with or without supplementation with formula feed. Factors that were found to have no significant association with the peak SB concentration were: gestational age; birthweight; the mode of delivery of the infants; maternal consumption of Chinese herbs and syntocinon induction or augmentation of labour.     

Glucose-6-phosphate dehydrogenase enzyme activity in normal, hemizygote and heterozygote Kelantanese Malays

This prospective study was performed to quantify glucose-6-phosphate dehydrogenase (G6PD) enzyme activity in deficient males and female heterozygotes. The methods used in the study were the fluorescent spot test, G6PD enzyme electrophoresis on cellulose acetate and quantitative assays. Forty-seven children who had been detected as spot screen deficient at birth were rescreened. Their first degree relatives were also included in the study. The mean enzyme activity of deficient males was 0.74 iu/g Hb (s.d. +/- 0.8), of female heterozygotes was 6.5 iu/g Hb (s.d. +/- 3.2) and of normal males was 12.1 iu/g Hb (s.d. +/- 3.5). The mean activity in deficient males was 6.1% of normal males. Most (35 of 47) of these fell into class 2 in Beutler's classification of G6PD variants. This indicates a population which may be susceptible to favism. Female heterozygotes had an intermediate enzyme activity with a wide scatter. Using a cut off point of enzyme activity of below 9.0 iu/g Hb gave sensitivity and specificity of 87% and 84% in detecting female heterozygotes. This group could be defined more accurately by combining quantitative assays with family studies.     

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］