漳州市葡萄糖-6-磷酸脱氢酶缺乏症筛查情况及其分子遗传学特征

目的 分析漳州市30 000例葡萄糖-6-磷酸脱氢酶（glucose 6-phosphate dehydrogenase,G6PD）缺乏症患儿的筛查情况及其分子遗传学特征。方法 选取2018年1月至2021年12月在漳州市出生的30 000例新生儿为研究对象,行新生儿足跟血滤纸干血片G6PD荧光斑点法测定,对筛查为阳性的患儿联合基因检测及G6PD活性酶学进行诊断,记录确诊情况及分子遗传学特征。结果 30 000例新生儿全部接受滤纸干血片G6PD荧光斑点法测定,初筛阳性新生儿1522例,初筛阳性率5.07%。经基因检测及G6PD活性酶学诊断,最终确诊1321例。共检出9种基因突变,其中以c.1024C>T、c.1376G>T、c.1388G>A为检出率最高的三种基因突变类型。c.487G>A、c.1360C>T两种基因型突变女性占比高于男性,其余基因型突变均为男性占比高于女性。按照致病性变异对最终确诊者分类后发现,以Ⅳ类为主,共861例,占65.18%（861/1321）。结论 漳州市新生儿中G6PD缺乏症发生率较高,且基因突变型较多,其中c.1388G>A型最为多见,且致病性分类以Ⅳ类为主,程度较轻。因此,应加强对新生儿G6PD缺乏症的筛查,提高疾病检出率。     

西双版纳州高疟区少数民族G6PD筛查

目的了解西双版纳州高疟区少数民族葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症情况,为间日疟患者的治疗和根治提供安全保障。方法按《云南省高疟区部分少数民族G6PD缺乏及其影响因素调查方案》,用纯化学反应荧法对5 807例高疟区少数民族的标本进行G6PD缺乏症的筛查。结果 5 807例标本中共筛查出G6PD缺乏261例,G6PD缺乏率为4.49%,G6PD缺乏率傣族居首位为9.22%,其后依次为瑶族6.99%、汉族3.39%、彝族2.41%、布朗族2.28%,拉祜族2.12%,哈尼族2.10%,傣族高于其它民族,差异均有统计学意义（P〈0.01）;男性G6PD缺乏率为6.51%,女性G6PD缺乏率为2.92%,男性高于女性,差异有统计学意义（P〈0.01）;G6PD缺乏率勐腊县居首为6.24%,依次为景洪市2.82%、勐海县2.47%,勐腊县高于勐海县和景洪市,差异有统计学意义（P〈0.01）。结论西双版纳州属G6PD缺乏症和疟疾感染的高发区,提示在间日疟患者的治疗和根治中应做好G6PD缺乏的筛查和流行病学调查,防止因治疗和根治药物引起的溶血反应。     

荧光PCR熔解曲线法检测广东韶关地区G6PD缺乏症基因突变

目的:采用荧光PCR熔解曲线法检测广东韶关地区G6PD缺乏基因突变,获得基因突变谱并进行方法学应用评价.方法:采用荧光PCR熔解曲线法试剂盒对613例G6PD缺乏症表型筛查阳性样本,分两管检测中国人群常见的12种G6PD基因突变(95A>G、383T>C、392G>T、487G>A、517T>C、592C>T、871G>A、1004C>A、1024C>T、1360C>T、1376G>T、1388G>A).结果:613例标本中检出基因突变536例(男性365例,女171例,占87.44%),其中:1388G>A突变210例(占37.30%),1376G>T突变213例(占37.83%),95A>G突变55例(占9.77%),871G>A突变49例(占8.70%),1024C>T突变18例(占3.20%),1004C>A突变2例(占0.35%),1360C>T突变4例(占0.71%),383T>C突变1例(占0.18%),392G>T突变10例(占1.78%),517T>C突变1例(占0.18%),没有发现487G>A、592C>T突变类型.另外,女性双重杂合或纯合突变分布情况为:1388G>A纯合突变7例,1376G>T纯合突变4例,871G>A纯合突变1例,1388G>A/1376G>T杂合突变4例,1388G>A/871G>A杂合突变2例,1388G>A/95A>G杂合突变1例,1376G>T/1024C>T杂合突变1例,1376G>T/95A>G杂合突变1例,1376G>T/392G>T杂合突变2例.结论:1388G>A,1376G>T,95A>G,871G>A,1024C>T,1004C>A,1360C>T,383T>C,392G>T,517T>C是韶关地区最常见的基因突变类型,与已报道的中国南方人群突变谱相近;荧光PCR熔解曲线法G6PD缺乏症基因结果准确,可广泛应用于临床基因检测.     

Prevalence of beta-thalassemia trait and glucose-6-phosphate dehydrogenase deficiency in Iranian Jews

BACKGROUND: beta-thalassemia is the most common inherited single gene disorder worldwide, and glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme deficiency. The goal of this study was to compare the frequency of beta-thalassemia trait and G6PD among the Moslem and Jewish populations in Shiraz, southern Iran. METHODS: We examined 201 Moslems and 187 Jewish subjects who were selected by random sampling. For diagnosis of thalassemia, complete blood count and hemoglobin electrophoresis were carried out and for G6PD deficiency, fluorescent spot test methods were used as a screening test. RESULTS: Among Moslem subjects, 14 cases (7.0%) were diagnosed as carriers of beta-thalassemia minor, whereas no carriers were detected among Jewish subjects. Seven Moslems (7%) and eight Jewish subjects (7.5%) were found to have G6PD deficiency. Among both groups the most common mutation was the Mediterranean type (563 C>T). In one Moslem subject, the detected mutation was 1003 (G>A) and in two Jewish subjects the mutations were 1376 (G>T) and G6PD A-. CONCLUSIONS: Whereas the frequency of beta-thalassemia minor among Moslems is higher than in the Jews in Shiraz, the frequency of G6PD deficiency was not significantly different in the two populations. These findings suggest that obligatory premarital beta-thalassemia screening for Jews in the community is not necessary, whereas neonatal screening for G6PD could be useful for both Jews and Moslems.     

Hereditary spherocytosis and glucose-6-phosphate dehydrogenase deficiency

The first reported case of hereditary spherocytosis (HS) and glucose-6-phosphate dehydrogenase deficiency in a black is presented. The recent literature is reviewed, with emphasis on the frequency of multiple inherited RBC defects in this ethnic group. Despite a coexisting hemoglobinopathy or enzyme deficiency, HS can be diagnosed in most cases by the peripheral blood smear, osmotic fragility curve, and family history. The implications of the double RBC abnormality are discussed, stressing the importance of splenectomy in relieving the hemolytic component due to spherocytosis.     

Erythrocyte glucose-6-phosphate dehydrogenase and glutathione deficiency in sheep

Erythrocytes of 145 sheep representing six breeds were assayed for glucose-6-phosphate dehydrogenase. All sheep had erythrocyte glucose-6-phosphate dehydrogenase values similar to glucose-6-phosphate dehydrogenase deficient erythrocytes of man. Mean erythrocyte glucose-6-phosphate dehydrogenase levels ranged from 0.65 to 1.54 micromoles of reduced nicotinamide adenine dinucleotide phosphate per gram of hemoglobin per minute. Many of these sheep also had low levels and/or unstable reduced glutathione. Sheep with low levels of erythrocyte glucose-6-phosphate dehydrogenase and reduced glutathione were given large doses of oxidizing drugs or fed fresh fava beans to determine if they would develop intravascular hemolysis. No significant hemolysis was detected as a result of drug administration or fava bean ingestion.     

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with asymptomatic malaria in a rural community in Burkina Faso

ObjectiveTo investigate 4 combinations of mutations responsible for glucose-6-phosphate dehydrogenase (G6PD) deficiency in a rural community of Burkina Faso, a malaria endemic country.MethodsTwo hundred individuals in a rural community were genotyped for the mutations A376G, G202A, A542T, G680T and T968C using TaqMan single nucleotide polymorphism assays and polymerase chain reaction followed by restriction fragment length polymorphism.ResultsThe prevalence of the G6PD deficiency was 9.5% in the study population. It was significantly higher in men compared to women (14.3% vs 6.0%, P=0.049). The 202A/376G G6PD A- was the only deficient variant detected. Plasmodium falciparum asymptomatic parasitaemia was significantly higher among the G6PD-non-deficient persons compared to the G6PD-deficient (P<0.001). The asymptomatic parasitaemia was also significantly higher among G6PD non-deficient compared to G6PD-heterozygous females (P<0.001).ConclusionsThis study showed that the G6PD A- variant associated with protection against asymptomatic malaria in Burkina Faso is probably the most common deficient variant.     

葡萄糖-6-磷酸脱氢酶缺乏对中性粒细胞的影响

目的：探讨我国常见葡萄糖-6-磷酸脱氢酶(G-6-PD)缺乏对外周血中性粒细胞内酶活性及产生活性氧能力的影响。方法：检测正常人及G-6-PD缺乏患者外周血中性粒细胞G-6-PD活性、mRNA表达水平及其在静止与应激状态下产生活性氧的能力(NBT试验)。结果：G-6-PD缺乏患者外周血中性粒细胞内G-6-PP酶活性较正常人显著下降，mRNA表达水平上升，产生活性氧的能力(NBT还原试验)在静止状态下较正常白细胞高，但无统计学意义，在脂多糖(LPS)刺激下低于正常白细胞。结论：我国常见的G-6-PD缺乏能使中性粒细胞G-6-PD活性、应激状态下产生活性氧的能力下降。     

婴儿葡萄糖-6-磷酸脱氢酶缺陷病的特点与预防

目的　探讨婴儿红细胞葡萄糖 - 6 -磷酸脱氢酶 (G - 6 -PD)缺陷病的特点与预防措施。方法　回顾分析 1995～ 2 0 0 0年儿内科住院的 1周～ 2个月 (不含 2个月 )的婴儿 310 4例 ,其中G - 6 -PD缺陷病患儿 2 39例。结果　G - 6 -PD缺陷病占同期住院患儿的 7 70 % ,占间接高胆红素血症患儿的 17 5 9% ,病死率为 5 0 2 % ,与肺炎的3 5 7%相近 (χ2 =0 88,P >0 0 5 )。合并高胆红素血症的占 10 0 0 0 % ,合并感染性疾病的占 38 4 9%、继发胆红素脑病的占 13 81%。结论　婴儿中G - 6 -PD缺陷病很常见 ,是高胆红素血症和胆红素脑病的首要病因 ,病死率也很高 ,提议将其列入本地区儿童疾病综合管理的范围 ,制定并推广预防的常规措施。     

贵阳地区新生儿G6PD缺乏症分子筛查结果分析

目的：了解贵阳地区葡萄糖‐6‐磷酸脱氢酶（G6PD ）缺乏症的发生率及基因突变分布情况。方法选取新生儿脐血DNA样本515例,采用基质辅助激光解吸／电离飞行时间质谱系统检测G6PD基因15种突变类型和1种多态位点。结果515份样本检出G6PD基因突变10例,检出率为1．94％。检出5种突变类型：1388G＞ A 4例（40．0％）,1024C＞ T 和519C＞ T各2例（20．0％）,1376G＞ T和95A＞G各1例（10．0％）。多态位点1311C＞T的等位基因频率为12．79％。结论贵阳地区是G6PD缺乏症的高发区,1388G＞A是该地区最常见的G6PD基因突变类型。     

Genetic polymorphisms in paraoxonase 1 and G protein-coupled receptor 77, and the risk of glucose-6-phosphate dehydrogenase deficiency in a Saudi population

Objectives:

To investigate the role of amino acid substitution variants Q192R and C698T in the development of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a Saudi male population.

Methods:

This case-control study was carried out in 200 Saudi male individuals: 100 patients with G6PD deficiency, and 100 control subjects collected between July and August 2011 in the Taif region of Saudi Arabia. A total of 2100 male Saudi individuals were screened by a fluorescence spot test, and 100 with G6PD deficiency were selected. Two common variants PON1 (rs662) and C5L2 (rs149572881) were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis.

Results:

The results showed that the R allele and QR genotype were associated with the Q192R polymorphism in PON1 (R versus Q odds ratio [OR], 1.72; 95% confidence interval [95% CI], 1.1-2.6; p=0.01; and QR versus QQ: OR, 1.98; 95% CI, 1.1-3.6; p=0.02). All the C698T genotypes and allele frequencies in C5L2 were almost similar in both the cases and controls (CT versus CC: OR, 2.04; 95% CI, 0.3-11.4; p=0.40; and T versus C: OR, 2.02; 95% CI, 0.3-11.1; p=0.41).

Conclusions:

These findings suggest the association of PON1 with G6PD deficiency in the Saudi male population studied herein. Future studies, including correlation analyses between the clinical features and genotypes in populations of different ethnicities, are warranted to confirm the disease association with these genetic mutations.The World Health Organization has confirmed glucose-6-phosphate dehydrogenase (G6PD; E.C.1.1.1.49), an x-linked genetic disorder, to be a public health concern.1 Glucose-6-phosphate dehydrogenase is an enzyme that converts glucose-6-phosphate into glucose-6-phosphogluconolactone. This conversion is the initial step for the pentose phosphate pathway, and G6PD plays an important role in protecting cells from oxidative damage.2-4 The G6PD is located at the tip of chromosome Xq28, with 13 exons and 12 introns, and it encodes a 515-amino acid protein. Its deficiency affects nearly 400 million people worldwide.5,6 The most common genetic variants in G6PD deficiencies are Mediterranean and A variants, which have been reported in Saudi Arabia.4,7,8 Specific genetic polymorphisms associated with G6PD abnormalities have been studied in male subjects in the past.4,6,9 No genetic studies on paraoxonase 1 (PON1) or G-protein coupled receptor (C5L2) have been performed in relation to G6PD deficiency. However, these genes have been shown to be associated with a Saudi population.10-12 This was the key motive for the selection of Q192R and C698T mutation/polymorphisms in G6PD deficiency in this study. Therefore, this study aimed to assess the genotypes of Q192R and C698T, previously associated with genetic, metabolic, and hereditary defects, in Saudi male subjects with G6PD deficiency.     

全自动荧光免疫分析仪在新生儿葡萄糖-6-磷酸脱氢酶缺乏症筛查中的应用

目的：分析全自动荧光免疫分析仪（GSP分析仪）检测新生儿葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症的性能。方法：应用GSP分析仪检测国家卫生健康委临床检验中心室间质量评价质控品和G6PD试剂盒（荧光分析法）的低、高质控品,计算准确度和精密度。采用GSP分析仪和半自动荧光免疫分析仪（1420分析仪）同步检测2622例新生儿筛查标本和41例确诊患儿的标本,分析检测结果的相关性和一致性;采用GSP分析仪和1420分析仪检测漂浮和未漂浮标本各78例,比较检测结果差异;采用1420分析仪和GSP分析仪分别检测2017年1月至2018年12月1?100?384名新生儿筛查标本及2019年1月至2020年12月855?856名新生儿筛查标本,比较两种仪器的筛查效能。对目前使用的切值（26?U/dL）的合理性进行评估,并通过百分位数法,以第99.1百分位建立GSP分析仪筛查G6PD缺乏症的新切值。结果：GSP分析仪检测5个不同浓度室间质控品的检测值与靶值的相对偏倚为0.71%~4.23%,检测G6PD测定试剂盒质控品的批内精密度为4.34%~4.91%,批间精密度为0.85%~2.12%,总变异系数为5.44%~5.72%,均符合实验要求。GSP分析仪和1420分析仪检测的G6PD活性存在明显的正相关（r=0.740,P<0.01）,均能筛查出41例确诊患儿,筛查的一致性较好（Kappa=0.945）。1420分析仪检测漂浮干血斑中的G6PD活性明显低于未漂浮干血斑中的G6PD活性（P<0.05）,而GSP分析仪检测漂浮和未漂浮干血斑中的G6PD活性差异无统计学意义（P>0.05）。GSP分析仪和1420分析仪筛查G6PD缺乏症的敏感度均为100.00%,且特异度均在99.80%以上。与1420分析仪比较,GSP分析仪筛查G6PD缺乏症的阳性预测值、初筛阳性率和诊断率均上升,假阳性率下降（均P<0.01）。根据人群第99.1百分位建立新切值,男性为26.1?U/dL,女性为29.1?U/dL。结论：GSP分析仪检测性能良好,筛查效率高,更有利于疾病的检出,可用于临床新生儿G6PD缺乏症的大规模筛查。     

Neonatal jaundice and glucose-6-phosphate dehydrogenase deficiency in Papua New Guinea.

Of 50 jaundiced neonatal patients studied at the Port Moresby General Hospital, 11 (22%) were found to be glucose-6-phosphate dehydrogenase-deficient. No apparent exogenous precipitating causes for the jaundice were noted. Serum bilirubin levels exceeded 20 mg/100 ml in seven of these glucose-6-phosphate dehydrogenase-deficient infants, and exchange transfusions were required for three subjects. Glucose-6-phosphate dehydrogenase deficiency must be considered in the differential diagnosis of neonatal jaundice in Papua New Guinea.     

玉溪市主要民族葡萄糖-6-磷酸脱氢酶缺乏调查

目的了解玉溪市主要民族葡萄糖-6-磷酸脱氢酶(G6PD)缺乏情况,为降低服用磷酸伯氨喹风险性提供依据。方法随机抽取玉溪市傣族、汉族、苗族、蒙古族和彝族五个民族人群,采集滤纸干血膜用纯化学反应荧光法进行红细胞G6PD活性检测。结果共检测1 523人,G6PD缺乏者63例,缺乏率为4.14%。其中,男性为4.92%,女性为3.83%,男、女差异无统计学意义(P0.05);傣族、汉族、苗族、蒙古族和彝族G6PD缺乏率分别为15.77%、3.26%、2.75%、0.67%、和0.66%,差异有统计学意义(P0.05),60~69岁年龄组G-6PD重度缺乏较高。结论玉溪市居民G6PD缺乏率高低及轻重情况与民族、年龄和区域性相关。提示在疟疾高度流行区重点居民G6PD的检测,应纳入基本公共卫生服务检查内容,以提高疟疾流行区居民服用伯氨喹磷的依从性,有效控制疟疾流行。     

新生儿G-6-PD缺乏症高未结合胆红素血症的心肌损害

目的 探讨新生儿G-6—PD缺乏症的高未结合胆红素血症对心肌损害。方法 30例G—6-PD缺乏症新生儿分别于入院时(治疗前)和治疗后(显性黄疸消退后)抽血测定心肌酶、肝功能、肾功能等,部分病人同时作心电图检查,并与15例正常新生儿进行比较。结果 30例G—6—PD缺乏症患儿心肌酶及同功酶活性均有不同程度增高,尤以CK—MB活性明显升高,两组比较差异有非常显著意义(P<0.01)。CK—MB升高与黄疸程度呈正相关(r=0.487、P<0.01)。治疗前后,高未结合胆红素心肌酶比较、差异有非常显著意义(P<0.01)。结论 新生儿高未结合肥红素血症可出现心肌损害,与黄道出现程度有关。