G6PD deficiency in senile cataracts

Summary The incidence of G6PD deficiency among 338 Thai males with senile cataracts was 5.92% while 446 control Thai males gave an incidence of 6.95%. The figures in females were 16.29% and 14% among 201 senile cataracts females and 200 control females respectively. The age of onset of senile cataracts was not different between the G6PD deficient and G6PD normal groups. The findings indicate that, at least in Thailand, G6PD deficiency in general is not a factor in cataractogenesis.     

G6PD Mediterranean accounts for the high prevalence of G6PD deficiency in Kurdish Jews

The Jews of Kurdistan are a small inbred population with a high incidence of -thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Recently, it was reported that the -thalassaemia in this population shows an unusual mutational diversity; 13 different mutations were identified, of which 4 had not previously been observed in any other population. In contrast, we now report that the G6PD deficiency, which has the highest known incidence in the world, and which affects about 70% of males, is almost entirely attributable to a single widespread mutation, G6PD Mediterranean.     

Neonatal screening of G6PD deficiency in Tunisia

The Glucose-6-phosphate dehydrogenase (G6PI) deficiency is the most common enzymopathy worldwide. WHO had classified Tunisia among countries that are moderately affected by this affection. However, no mass-screening reflecting the real incidence was realized. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis in Tunisia. A total of 1102 neonates, born in CMNT center of Maternity and of Neonatology of Tunis during the going periods from April, 2005 till May, 2005 and from June, 2006 till September, 2006, have been enclosed in the study. The samplings included 953peripheral venous blood and 149 blood cordon. Among 1102 samplings, only 976 were of use to the screening. In our mass-screening, we consider all newborns that were born in the CMNT during the period of study and were included in the screening. A dosage of the enzymatic activity was realized using spectrophotometric method. G6PD electrophoresis and molecular study by PCR/RFLP were realized for the overdrawn newborn children. Among 976 screening neonates, 43 individuals (4.4%) were found to be G6PD deficient by quantitative enzyme assay. Newborn affected were distributed in 23 boys and 20 girls (sex ratio of 1.15). The electrophoretic mobility and the molecular biology were realized for the affected newborn. Molecular characterization of 30 G6PD deficient neonates revealed that the G6PD A- was the most common and was detected in 20 of 43 individuals (66.7%), followed by G6PD Mediterranean that was detected in 6 (13.3%). At least, 4 other unknown mutations were not able to be determined by PCR/RFLP (n=4). In conclusion G6PD deficiency is frequent in our country, justifying a systematic neonatal screening, to avoid the arisen of grave consequences of this affection. The African variant is the most frequent in our country followed by the Mediterranean one.     

Molecular analysis of three novel G6PD variants: G6PD Pedoplis-Ckaro, G6PD Piotrkow and G6PD Krakow

We present three novel mutations in the G6PD gene and discuss the changes they cause in the 3-dimensional structure of the enzyme: 573C-->G substitution that predicts Phe to Leu at position 191 in the C-terminus of helix alphae, 851T-->C mutation which results in the substitution 284Val--> -->Ala in the beta+alpha domain close to the C-terminal part of helix alphaj, and 1175T-->C substitution that predicts Ile to Thr change at position 392.     

Analysis of G6PD enzyme deficiency in Saudi population

The evolutionary conservation of a housekeeping gene such as G6PD is greater than that of tissue-specific genes, presumably because the latter may require more specific adaptation to the physiology of individual organisms. The abundance of distinct mutation sites and their clinical manifestations make G6PD ideal for structure-function analysis. Therefore, it is of interest to screen of G6PD deficiency in the blood donors in Kingdom of Saudi Arabia. We report the mean and variation of enzyme activity in a huge set of Suadi to non-Saudi population with reference to the entire population. The sequence level conservation of G6PD among distant species is demonstrated using phylogenetic trees. These observations have implications in the sequence-structure-function understanding of G6PD with reference to its association to several human diseases.     

Genetic heterogeneity of G6PD deficiency: mutant alleles of G6PD in the Shekii district of Azerbaijan]

Examination on G6PD deficiency in 349 patients of Shekii district hospital (Azerbaijan) revealed 16 hemi-, 4 homo- and 9 heterozygotic carriers of the defect. Gd- frequency, calculated from the data obtained (7.7%), may be compared to neighbouring regions' frequencies (6-30%). Carriers of G6PD deficiency are residents of 11 villages located in Alasani-Aphtalan valley, highly endemic with malaria in the past; nearly all marriages are endogamic. Physico-chemical and kinetic study of 10 mutant forms of G6PD, according to WHO program, led to identification of 5 variants of the II class (Shekii, Bideiz, Shirin-Bulakh, Okhut I and Zakataly) and 2 variants of the III class (Okhut II and Martinique-like). Resemblance of the majority of variants in electrophoretic mobility and the level of erythrocyte enzyme activity permit to suggest the existence of a common parental mutant G6PD allele distributed in this area.     

G6PD deficiency, diet, and adaptation to malaria

The symposium on “G6PD Deficiency, Diet, and Adaptation to Malaria” was held in Cortona, Italy on July 3,4,5 1995 under the auspices of the Congress of the International Union of Anthropological and Ethnological Sciences (IUAES). The Congress had actually taken place in Florence in April 1995, and the G6PD symposium was a satellite session to that meeting. Professor Brunetto Chiarelli, of the Istituto di Antropologia at the University of Florence, was the program chairman for the Congress. The general theme of the Congress was “Biodemography and Human Evolution,” and the G6PD symposium was consistent with this topic. In its broadest sense the symposium focused on biocultural factors which have influenced evolution at the G6PD locus and the pattern of population variation that has consequently emerged in this genetic system. A more specific sub-theme, reflected in the title of the symposium, was the interaction between dietary factors and the G6PD locus in providing antimalarial protection to human populations.     

G6PD Toronto

Members of a Toronto family of Northern European ancestry were found to have a deficiency of red cell and white cell glucose 6-phosphate dehydrogenase (G6PD) activity. The hemizygous propositus had neonatal hyperbilirubinemia and subsequent episodes of hemolytic jaundice associated with respiratory infections and exposure to paint fumes. Characterization of the enzyme revealed that it was a variant which had not been previously described, and it was named 6GPD Toronto.This study was supported by grants MT 696 from the Medical Research Council of Canada and GM 15253 from the National Institutes of Health.     

G6PD-MutDB: a mutation and phenotype database of glucose-6-phosphate (G6PD) deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary enzymatic disorder of red blood cells in humans due to mutations in the G6PD gene. The G6PD enzyme catalyzes the first step in the pentose phosphate pathway to protect cells against oxidative stress. Mutations in the G6PD gene will cause functional variants with various biochemical and clinical phenotypes. So far, about 160 mutations along with more than 400 biochemical variants have been described. G6PD-MutDB is a disease-specific resource of G6PD deficiency, collecting and integrating G6PD mutations with biochemical and clinical phenotypes. Data of G6PD deficiency is manually extracted from published papers, focusing primarily on variants with identified mutation and well-described quantitative phenotypes. G6PD-MutDB implements an approach, CNSHA predictor, to help identify a potential chronic non-spherocytic hemolytic anemia (CNSHA) phenotype of an unknown mutation. G6PD-MutDB is believed to facilitate analysis of relationship between molecular mutation and functional phenotype of G6PD deficiency owing to convenient data resource and useful tools. This database is available from http://202.120.189.88/mutdb.     

Hemoglobinopathies, G6PD deficiency, and hereditary elliptocytosis in Bahrain

The native population of Bahrain has a high prevalence of hemoglobinopathies and G6PD deficiency, probably as a result of past malarial endemism. We used the Biorad-Variant hemoglobin testing system for primary screening of hemoglobinopathies in 20,000 individuals. Hemoglobin abnormalities were detected in 7,206 (36.3%) cases.     

Moderate G6PD deficiency increases mutation rates in the brain of mice

Mice that harbored the x-ray-induced low efficiency allele of the major X-linked isozyme of glucose-6-phospate dehydrogenase (G6PD), Gpdx(a-m2Neu), and, in addition, harbored the transgenic shuttle vector for the determination of mutagenesis in vivo, pUR288, were employed to further our understanding of the interdependence of general metabolism, oxidative stress control, and somatic mutagenesis. The Gpdx(a-m2Neu) mutation conferred moderate G6PD deficiency in hemizygous males (Gpdx(a-m2Neu/y)) displaying residual enzyme activities of 27% in red blood cells and 13% in brain (compared to wild-type controls, Gpdx(a/y) males). In spite of this mild phenotype, the brains of G6PD-deficient males exhibited a significant distortion of redox control ( approximately 3-fold decrease in the ratio of reduced glutathione to oxidized glutathione), a considerable accumulation of promutagenic etheno DNA adducts ( approximately 13-fold increase in ethenodeoxyadenosine and approximately 5-fold increase in ethenodeoxycytidine), and a substantial elevation of somatic mutation rates ( approximately 3-fold increase in mutant frequencies in lacZ, the target and reporter gene of mutagenesis in the shuttle vector, pUR288). The mutation pattern in the brain was dominated by illegitimate genetic recombinations, a presumed hallmark of oxidative mutagenesis. These findings suggested a critical function for G6PD in limiting oxidative mutagenesis in the mouse brain.     

G6PD Avenches and G6PD Moosburg: biochemical and erythrocyte membrane characterization

Two new G6PD variants with severe enzyme deficiency in Switzerland (G6PD Avenches, G6PD I) and in Germany (G6PD Moosburg, G6PD II) are described. One patient had suffered from severe postpartal hyperbilirubinemia, the other one presented with chronic hemolysis and remittent hyperbilirubinemia. Both variants showed diminished electrophoretic mobility, both variants were heat labile. The Michaelis-Menten constants KM for glucose-6-phosphate and for NADP+ were normal. 2-Desoxy-glucose-6-phosphate was utilized by G6PD I in a higher and by G6PD II at a lower rate than by the normal enzyme. Desamino-NADP+ and galactose-6-phosphate were utilized by both variants at a normal rate. The electrophoretic separation of membrane proteins of G6PD II showed both in the presence and in the absence of 6-mercaptoethanol no difference concerning the formation of membrane protein aggregates between patient and normal control.     

Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria

BackgroundPlasmodium vivax occurs as a latent infection of liver and a patent infection of red blood cells. Radical cure requires both blood schizontocidal and hypnozoitocidal chemotherapies. The hypnozoitocidal therapies available are primaquine and tafenoquine, 8-aminoquinoline drugs that can provoke threatening acute hemolytic anemia in patients having an X-linked G6PD-deficiency. Heterozygous females may screen as G6PD-normal prior to radical cure and go on to experience hemolytic crisis.Methods & findingsThis study examined G6PD phenotypes in 1928 female subjects living in malarious Sumba Island in eastern Indonesia to ascertain the prevalence of females vulnerable to diagnostic misclassification as G6PD-normal. All 367 (19%) females having <80% G6PD normal activity were genotyped. Among those, 103 (28%) were G6PD wild type, 251 (68·4%) were heterozygous, three (0·8%) were compound heterozygotes, and ten (2·7%) were homozygous deficient. The variants Vanua Lava, Viangchan, Coimbra, Chatham, and Kaiping occurred among them. Below the 70% of normal G6PD activity threshold, just 18 (8%) were G6PD-normal and 214 (92%) were G6PD-deficient. Among the 31 females with <30% G6PD normal activity were all ten homozygotes, all three compound heterozygotes, and just 18 were heterozygotes (7% of those).ConclusionsIn this population, most G6PD heterozygosity in females occurred between 30% and 70% of normal (69·3%; 183/264). The prevalence of females at risk of G6PD misclassification as normal by qualitative screening was 9·5% (183/1928). Qualitative G6PD screening prior to 8-aminoquinoline therapies against P. vivax may leave one in ten females at risk of hemolytic crisis, which may be remedied by point-of-care quantitative tests.     

In vitro correction of erythrocyte glucose 6-phosphate dehydrogenase (G6PD) deficiency.

The permeability characteristics of egg phosphatidylcholine (EPC) vesicles to Eu³⁺ has been examined by ³¹P-nmr, in various mixed lipid systems. It has been found that incorporation of small amounts of sodium taurocholate (NaTC) in the EPC vesicle greatly increased the vesicular permeability to Eu³⁺. Incorporation of cholesterol in the EPC vesicle significantly inhibits the ability of NaTC to induce permeability alterations in this mixed system. It has been reported that at low EPC:NaTC ratios (2:1-0.65:1), mixed micelles of the components are formed [N. A. Mazer, R. F. Kwasnick, M. C. Carey, and G. B. Benedek, 1977, in Micellization, Solubization, and Microemulsions (Mittal, K. L., ed.) Vol. 1, pp. 483-402, Plenum Press, New York]. By examination of the ³¹P-nmr linewidths of EPC, at various ratios of EPC:NaTC, it is possible to follow the decrease in size of the EPC vesicle, as it becomes incorporated into the smaller NaTC micelles. The ³¹P{¹H} nuclear Overhauser enhancement of the simple EPC vesicle is not significantly different from this same parameter measured for EPC, when it exists in mixed micellar systems with NaTC. This indicates that there must be considerable internuclear head group interactions of EPC molecules in EPC-NaTC mixed micelles. This argues for sequestering of EPC in such micelles.