Hypoglycemia-induced hemolysis in glucose-6-phosphate dehydrogenase deficiency

We present a young man with Mediterranean type glucose-6-phosphate dehydrogenase (G6PD) deficiency and insulin-dependent diabetes mellitus whose brittle course was characterized by recurrent bouts of hypoglycemia and diabetic ketoacidosis (DKA). While neither of the episodes of DKA was complicated by hemolysis, hemolytic anemia consistently followed the recurrent attacks of hypoglycemia. Stringent control of the patient's blood glucose levels in the upper limit and slightly above the normal range successfully prevented recurrence of hypoglycemia and recrudescence of hemolytic anemia. Hypoglycemia is proposed as capable of inducing hemolysis in G6PD deficiency.     

Cortisol metabolism in glucose-6-phosphate dehydrogenase deficiency

Ten subjects with glucose-6-phosphate dehydrogenase deficiency (G6PD Canton) and ten G6PD normal subjects matched for sex and age distribution were studied with respect to their plasma cortisol levels and 24-hr urinary total 17-oxogenic steroids excretion before and after maximal stimulation with B^1–24 corticotrophin (Synacthen depot). In five patients and five controls, the study included the metabolic clearance rate of cortisol which increased twofold after B^1–24 corticotrophin administration. No significant differences were found in these two groups of individuals. This indicates that in G6PD-deficient subjects, under basal conditions and with maximal stimulation, both cortisol production and metabolism proceed at a normal rate.     

葡萄糖-6-磷酸脱氢酶缺乏症的研究进展

葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症是人类最常见的遗传性细胞酶病，在全世界约有4亿多人受累，在一些国家和地区也已成为一个重要的公共卫生问题。G6PD缺乏症多分布于非洲热带、亚洲热带和亚热带、中东、地中海和巴布亚一新几内亚地区。该文对G6PD缺乏症的流行病学、遗传学、分子生物学、临床表现和诊断等方面的研究进展作一综述。     

Biochemical mechanisms of glucose-6-phosphate dehydrogenase deficiency.

A solid-phase radioimmunoassay for human glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase; EC 1.1.1.49) was developed that allowed the specific activity of this enzyme protein to be measured in lysates from whole erythrocyte populations, in lysates from erythrocytes of different ages, and in purified samples. The enzyme was highly purified from erythrocytes of single donors by a simple procedure of affinity chromatography with insolubilized adenosine 2',5'-bisphosphate. These techniques were used in an attempt to elucidate the molecular mechanisms leading to deficiency of glucose-6-phosphate dehydrogenase activity in two genetic variants of the enzyme, i.e., the Mediterranean and the Seattle-like variants. The results indicate that the lowered activity of erythrocytes containing the Mediterranean variant of glucose-6-phosphate dehydrogenase is related to an enhanced rate of degradation of a catalytically defective protein synthesized at a nearly normal rate. Synthesis of a normally functioning protein and an increased breakdown of it are involved in the Seattle-like variant of the enzyme.     

The value of screening tests for glucose-6-phosphate dehydrogenase deficiency

The performances of two commercial screening tests for glucose-6-phosphate dehydrogenase deficiency (Sigma fluorescent spot test and Sigma colorimetric method) were assessed in order to determine their usefulness in a routine haematology laboratory. As a first step, three ranges for enzyme activity were determined as follows: a 'normal' range determined from the 95% confidence limit of assays carried out on 114 normal adult males, a deficient range calculated as 25% of the upper limit of normal or less, and an intermediate range between the lower and upper values of these ranges. These values were 4.9-11.8 u/g Hb, 0-2.9 u/g Hb and 3.0-4.8 u/g Hb respectively. A separate normal range was also determined for females and was 5.5-12.8 u/g Hb. The two screening tests were then assessed against these values and the kits were found to be equally reliable at predicting normals and deficients but less reliable at detecting all female heterozygotes. The criteria for using the different procedures were evaluated. It is concluded that screening procedures are useful only when a large number of tests are routinely performed or in the absence of facilities for assays, as they offer no advantage in cost or time over the assay procedure. The colorimetric test (single vials) is easier and cheaper to use if isolated tests are performed, whereas the fluorescent spot test (with some modifications) is more useful for carrying out numerous tests simultaneously.     

Association of glucose-6-phosphate dehydrogenase deficiency with diabetes mellitus

The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency was estimated in 318 diabetic patients using Beulter's fluorescent Spot test. A significantly (p less than 0.001) higher prevalence of G6PD deficiency was detected among diabetic patients (19.6%) as compared to controls (10.4%). The distribution of G6PD deficiency varied with age, sex, and duration of diabetes. Among diabetic men, the prevalence of deficiency was significantly higher than controls in both age groups; 40 years and below, and 41 years and above (p less than 0.005 and p less than 0.02, respectively). Among diabetic women, the significantly higher prevalence of deficiency was observed only in the young age group (p less than 0.005), whereas the difference among the older age group was not significant (p greater than 0.1). A significant increase in the prevalence of deficiency with increase in duration of diabetes was detected among men (p less than 0.05), but not in women. The results of the study suggest a positive association between G6PD deficiency and diabetes mellitus.     

Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Jordan

Molecular screening for glucose-6-phosphate (G6PD) mutations in two Jordanian populations revealed six different mutations and higher incidences of G6PD deficiency and G6PD A- (376A-->G + 202G-->A) mutation in Jordan Valley than in the Amman area. These observations may be explained by historically higher rates of malaria and African ancestral origins, respectively.     

Prevalence of glucose-6-phosphate dehydrogenase deficiency in Northern Greece

Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects more than 400 million persons worldwide. Its distribution varies significantly among different geographic regions and different population groups. Purpose of our study was to estimate its prevalence in Northern Greece. The dataset comprised 5161 newborns and adults who were screened for G6PD deficiency between July 2001 and March 2007. G6PD deficiency was detected by the dye reduction method. In the screened group, 6.3% of subjects were G6PD deficient. Moderate enzyme deficiency was shown in 139 individuals (2.7%). Complete deficiency was identified in 3.7%. The prevalence of G6PD deficiency in Northern Greece is much higher compared with the general Greek population. Moreover, G6PD prevalence in the male sex is much higher - almost double - that in the female sex.     

Neonatal screening for glucose-6-phosphate dehydrogenase deficiency in Taiwan

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathic disease in Taiwan. The mass neonatal screening of G6PD deficiency by fluorometric spot test in Taiwan was started with a pilot program in 1984. The nationwide screening was started on July 1, 1987, and a follow-up system comprising of eighteen referral hospitals, including outlying islands, was organized for confirmatory test, medical care and genetic counseling. From July 1987 to December 1997, 2,971,192 heel blood samples collected on filter paper from 1,143 delivery units were screened by four neonatal screening centers. 46,570 cases were confirmed as G6PD deficiency is estimated to be around 2.1% (male 3.1%, female 0.9%) in Taiwan. The coverage rate of neonatal screening was 99% in 1997. To assess the reliability of the confirmatory test, an external quality assurance (QA) program for G6PD assay was developed. Periodically, 3 or 5 lyophilized quality control materials with different activities of G6PD were sent to each referral hospital by speed post delivery in dry ice. From January 1988 to June 1998, 85 QA services were performed. Two hundred and seven (13.5%) abnormal QA results were found, which were attributed to clerk (11.6%), procedural (16.4%), and instrumental errors (47.3%). In aid to confirm G6PD deficiency, a method to detect the G6PD mutation by using the dried blood samples was developed. The frequencies of the mutant alleles in Taiwan were determined to be 46.8% (1376G > T), 16.2% (1388G > A), 7.9% (95A > G), 6.5% (493A > G), 5.6% (392G >T), 4.6% (1024C > T), 0.5% (487G > A) and 0.5% (519C > G), respectively.     

Genotype and phenotype correlation in glucose-6-phosphate dehydrogenase deficiency

BACKGROUND AND OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythrocytic enzymatic disorder in Italy and is characterized by wide clinical, biochemical and molecular variability. We studied the clinical and hematologic data from 54 G6PD-deficient, unrelated males from the Apulia region. DESIGN AND METHODS: Analyses for enzymatic activity, G6PD electrophoresis and molecular typing were performed on all subjects. Thirty-nine subjects (72.2%) showed a severe G6PD deficiency (<10% residual enzymatic activity) and 15 subjects (27.8%) a moderate deficiency (10--60% residual activity). RESULTS: The Mediterranean variant was found in 48.2% of cases, the Seattle variant in 33.3%, the A- variant in 7.45% and the Montalbano variant in 3.7%; the variant was not identified in four subjects. Thirty-two patients (59.2%) were asymptomatic; of these, 37.04% demonstrated acute hemolytic crises induced mainly by ingestion of fava beans and 3.7% had had neonatal jaundice. Acute hemolytic anemia was found in 53.8% of subjects with the Mediterranean variant, in 5.5% with the Seattle variant, in 100% with the A-variant and 0% with the Montalbano variant. INTERPRETATION AND CONCLUSIONS: Enzymatic activity was shown to be a poor predictive parameter of acute hemolytic crises and was not correlated with clinical features. Subjects with Mediterranean or A- variants had a more severe clinical phenotype which was not related to enzymatic activity. The Seattle, and probably the Montalbano, variant appears to have a milder clinical expression.     

葡萄糖-6-磷酸脱氢酶缺乏症患者心脏外科围手术期观察

目的 观察葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症患者心脏体外循环围手术期治疗方法.方法 以2005年1月至2010年12月间在广西桂林医学院附属医院中进行心脏手术的10例G6PD缺乏症确诊患者作为病例组观察对象.同期选取性别、年龄、体质量、所患心脏手术疾病相匹配的20例非G6PD缺乏症患者作为对照组观察对象.病例组患者围手术期治疗措施集中于避免药物引起的急性溶血反应,减少手术应激,采用浅低温体外循环,加强血液保护等.观察指标包括患者围手术期呼吸机辅助时间、尿量、胸管引流量、输红细胞悬液量、输血浆量、术后第2天血红蛋白和血总胆红素水平,重症监护病房(ICU)停留时间等.结果 病例组呼吸机辅助时间[(8.6±5.7)h]、尿量[(1950±490)ml]、胸管引流量[(260±l20)ml]、输红细胞悬液量[(1.8±1.2)U]、输血浆量[(80±50)ml]、术后第2天血红蛋白[(99±12) g/L]和总胆红素水平[(27±11)μmol/L]与对照组比较[(9.3±4.5)h、(2100±670)ml、(253±146)ml、(1.3±1.0)U、(120±50)ml、(96±25)g/L、(24±8)μmol/L],差异均无统计学意义(t值分别为0.978、2.032、1.257、0.891、2.182、2.271、1.329,P均＞0.05),但病例组ICU停留时间[(2.6±0.6)d]较对照组[(1.8±1.5)d]明显增长(t=2.704,P＜ 0.05).结论 G6PD缺乏症患者心脏体外循环手术时,加强围手术期处理效果较好.