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PubMed2000

Glucose-6-phosphate dehydrogenase deficiency neonatal screening: preliminary evidence that a high percentage of partially deficient female neonates are missed during routine screening.

OBJECTIVES: To provide preliminary evidence that the currently employed semiquantitative method of screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency can only detect infants who are totally deficient for G6PD and misses all cases of partial G6PD deficiency. SETTING: General population: 2150 randomly selected blood samples from the Blood Donation Department, Speliopouleion General Hospital, Athens, Greece. Neonate population: 2000 samples from neonates (50% male; 50% female) in maternity hospitals in the greater Athens area. High risk population: a total of 545 individuals from 133 families in the Athens area, the minimum acceptance criteria being the parents and any brother or sister. METHOD: Blood specimens from neonates or adults were collected and either spotted and dried on special filter paper (Schleicher and Schull 2992, Darmstadt, Germany) or used in tubes after being heparinised. For the quantitative evaluation of G6PD enzyme activity, the Quantase G6PD screening kit (Quantase Limited, Perth, UK) was used. Quantase G6PD controls (Quantase Limited) were used at three levels of G6PD. These controls are rated at 24, 30, and 37 degrees C. Alternatively, we used the Sigma G6PDH controls (Sigma Chemical Company, St Louis, USA) which are rated at 30 and 37 degrees C. The assay was performed according to the instructions included in the kit with the modification for haemoglobin normalisation. RESULTS: General population: 36 females who were classified as having normal enzymatic activity with the semiquantitative test, were classified as partially deficient with the quantitative test. Neonate population: using the quantitative test, the percentage of G6PD deficient neonates in this population was 5.5%, compared with 3.17% reported in routine screening using the semiquantitative method. High risk population: the quantitative method detected 28 cases of total or partial G6PD deficiency in sisters of males with known total deficiency. The semiquantitative CONCLUSIONS: A considerable amount of partially G6PD deficient female neonates (heterozygotes) are undetected and classified as having normal enzymatic activity using the semiquantitative method, which uses a cut off of 2.1 U/g haemoglobin (Hb). The use of a fully quantitative G6PD screening kit is proposed, employing the automated haemoglobin normalisation and a cut off of 6.4 U/g Hb. Any neonate with an activity below this mark should be regarded as G6PD deficient, and all preventive measures should be taken.

Clinical Enzyme Tests↗
PubMed2005

Augmented IL-10 production and redox-dependent signaling pathways in glucose-6-phosphate dehydrogenase-deficient mouse peritoneal macrophages.

Glucose-6-phosphate dehydrogenase (G6PD) supports cellular antioxidant pathways. G6PD deficiency is associated with malaria protection but was shown to worsen the clinical course to injury. This study tested whether G6PD deficiency manifests in altered cytokine responses using peritoneal macrophages from a G6PD-deficient mouse model with a degree of defect similar to the common type A(-) human G6PD deficiency. Lipopolysaccharide (LPS)-induced interleukin (IL)-10 and IL-12 production was doubled in G6PD-deficient macrophages compared with wild-type (WT). Protein kinase C (PKC) activation by phorbol-ester prior to LPS resulted in a fivefold greater IL-10 production in G6PD-deficient macrophages compared with WT. Interferon-gamma treatment prior to LPS augmented IL-12 production in G6PD-deficient and WT macrophages and partially inhibited IL-10 production by G6PD-deficient macrophages. The antioxidants (N-acetyl-L-cysteine and glutathione ethyl-ester) blunted IL-10 and IL-12 production, indicating a role for oxidative stress in the observed response differences between deficient and WT macrophages. LPS-induced activation of nuclear factor-kappaB, cyclic adenosine monophosphate response element-binding protein, and specificity protein 3 was augmented in G6PD-deficient cells compared with WT. The PKCdelta inhibitor Rottlerin inhibited IL-10 and IL-12 production at different 50% effective-dose concentrations between deficient and WT macrophages, indicating elevated PKCdelta activity in deficient cells. This study reveals that activated G6PD-deficient macrophages display an augmented production of cytokines with a prominent impact on IL-10 production. The altered cytokine responses are associated with augmented activation of redox-dependent transcription factors and PKCdelta. Alterations in signaling pathways and associated changes in cytokine production may play a role in modulating the inflammatory responses following bacterial or malarial infections in G6PD deficiency.

Animals↗
PubMed2005

[Glucose-6-phosphate dehydrogenase gene mutations in She nationality, Fujian province].

OBJECTIVE: To analyze the genotypes of glucose-6-phosphate dehydrogenase (G6PD) gene mutations, and investigate the incidence of G6PD deficiency and gene frequency in She Nationality (SN) in Fujian province. METHODS: G6PD deficiency was screened by NBT method, G6PD mutations identified by amplification refractory mutation system (ARMS), mismatch-PCR with a restriction endonuclease, PCR-SSCP and DNA sequencing. RESULTS: Among 1820 Qingshui SN and 764 Muyun SN, 101 and 104 samples were found to be abnormal, and the G6PD gene frequency accounted for 0.0607 and 0.1706 respectively. Among 54 pure ethnic descent SN samples in Muyun SN, 38 were identified as 1376G-->T, 10 as 1388G --> A and 6 as 95A-->G. The frequencies were 70.3%, 18.5% and 11.1% respectively. One case with both 1388G-->A and 95A-->G and another case with both 1376G-->T and 1388G-->A. Six 1024C-->T and one 392G -->T in Qingshui SN were identified. CONCLUSIONS: (1)G6PD nt1376G-->T and G6PD nt1388G-->A are two main variants in Muyun SN. Chinese ethnic groups share the similar G6PD gene variants, suggesting originated from the same ancestor. (2) 5 variants are found in SN: G6PD nt1376G-->T, nt1388G-->A, nt95A-->G, nt1024C-->T and nt392G-->T. (3) One with both nt1376G-->T and nt95A-->G mutations, another with both nt1376G-->T and nt1388G-->A mutations were found in SN. (4) nt95A-->G is another common G6PD gene variant in Muyun SN; nt1024C-->T is a common G6PD gene variant in Qingshui SN. (5)The gene frequency of G6PD in Qingshui SN is 0.0607, and is 0. 1706 in Muyun SN, these would facilitate the policy decision of C6PD deficiency prevention and treatment in these areas.

Asian People↗
PubMed1995

Glucose-6 phosphate dehydrogenase mutations and haplotypes in various ethnic groups.

Mutations that produce glucose-6-phosphate dehydrogenase (G6PD) deficiency have been identified in samples from patients with hemolytic disease in the United States, and in G6PD-deficient samples from Greece, the Canary Islands, the Czech and Slovak Republics, South China, and in samples from the Coriell Cell Repository. Eight new mutations are described. Particularly unusual were a nonsense mutation ("G6PD Georgia"1284A), a deletion of six bases ("G6PD Stony Brook" 724-729 del) coding for two amino acids, and a deletion of the invariant dinucleotide ApG at the 3' acceptor splice site in the highly conserved sequence between intron 10 and exon 11 ("G6PD Varnsdorf"). In addition, five new missense point mutations were identified: "G6PD Cleveland"820A creates a deduced AA 274 Glu-->Lys; "G6PD West Virginia"910T AA 303 Val-->Phe; "G6PD Fushan"1004A, AA 335 Ala-->Asp; "G6PD Olomouc"1141C AA 381 Leu-->Phe; and "G6PD Praha"1166G AA 389 Glu-->Gly. All of the new mutations except for "G6PD Fushan"1004A were found in patients with hereditary nonspherocytic hemolytic anemia. A coincidental finding in the case of G6PD "West Virginia" was a C-->T transition at nucleotide 1,191. This silent mutation, Asn-->Asn, appears to be rare. Haplotype analysis of mutations in samples from the Canary Islands and South China agreed with previous findings.

Anemia, Hemolytic↗
PubMed2003

Glucose-6-phosphate dehydrogenase partitioning in two-phase aqueous mixed (nonionic/cationic) micellar systems.

The enzyme glucose-6-phosphate dehydrogenase (G6PD) plays an important role in maintaining the level of NADPH and in producing pentose phosphates for nucleotide biosynthesis. It is also of great value as an analytical reagent, being used in various quantitative assays. In searching for new strategies to purify this enzyme, the partitioning of G6PD in two-phase aqueous mixed (nonionic/cationic) micellar systems was investigated both experimentally and theoretically. Our results indicate that the use of a two-phase aqueous mixed micellar system composed of the nonionic surfactant C(10)E(4) (n-decyl tetra(ethylene oxide)) and the cationic surfactant C(n)TAB (alkyltrimethylammonium bromide, n = 8, 10, or 12) can improve significantly the partitioning behavior of G6PD relative to that obtained in the two-phase aqueous C(10)E(4) micellar system. This improvement can be attributed to electrostatic attractions between the positively charged mixed (nonionic/cationic) micelles and the net negatively charged enzyme G6PD, resulting in the preferential partitioning of G6PD to the top, mixed micelle-rich phase of the two-phase aqueous mixed micellar systems. The effect of varying the cationic surfactant tail length (n = 8, 10, and 12) on the denaturation and partitioning behavior of G6PD in the C(10)E(4) /C(n)TAB/buffer system was investigated. It was found that C(8)TAB is the least denaturing to G6PD, followed by C(10)TAB and C(12)TAB. However, the C(10)E(4)/C(12)TAB/buffer system generated stronger electrostatic attractions with the net negatively charged enzyme G6PD than the C(10)E(4)/C(10)TAB/buffer and the C(10)E(4)/C(8)TAB/buffer systems, when using the same amount of cationic surfactant. Overall, the two-phase aqueous mixed (C(10)E(4)/C(10)TAB) micellar system yielded the highest G6PD partition coefficient of 7.7, with a G6PD yield in the top phase of 71%, providing the optimal balance between the denaturing effect and the electrostatic attractions for the three cationic surfactants examined. A recently developed theoretical framework to predict protein partition coefficients in two-phase aqueous mixed (nonionic/ionic) micellar systems was implemented, and the theoretically predicted G6PD partition coefficients were found to be in reasonable quantitative agreement with the experimentally measured ones.

Animals↗
PubMed1991

Some Mexican glucose-6-phosphate dehydrogenase variants revisited.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency appears to be fairly common in Mexico. We have now examined the DNA of three previously reported electrophoretically fast Mexican G6PD variants, -G6PD Distrito Federal, G6PD Tepic, and G6PD Castilla. All three of these variants, believed on the basis of biochemical characterization and population origin to be unique, have the G----A transition at nucleotide 202 and the A----G transition at nucleotide 376, mutations that we now recognize to be characteristic of G6PD A-. Two other Mexican males with G6PD deficiency were found to have the same mutation. All five have the (NlaIII/FokI/PvuII/PstI) haplotype characteristic of G6PD A -in Africa. Since the PvuII+ genotype seems to be rare in Europe, we conclude that all of these G6PD A - genes had their ancient origin in Africa, although in many of the Mexican patients with G6PD A -202A/376G the gene may have been imported more recently from Spain, where this variant, formerly known as G6PD Betica, is also prevalent.

DNA↗
PubMed1990

Quantitation of glucose-6-phosphate dehydrogenase mRNA by solution hybridization: correlation with rates of synthesis.

Rat liver glucose-6-phosphate dehydrogenase (G6PD) is one of several proteins involved in lipid metabolism whose synthesis is regulated by diet. In experiments reported here, rats were fasted or fed diets until a new steady state level of G6PD was produced. Livers were used to measure G6PD activity, synthesis and mRNA simultaneously. Since accurate quantitation of G6PD mRNA by Northern blots was found to be difficult in noninduced animals a new solution hybridization assay was also used. Noninduced rats have approx. One molecule of G6PD mRNA per liver cell. Changes in G6PD mRNA are larger than previously reported and, at the steady state, can completely account for the 33-fold change in G6PD activity and synthesis when fasted rats are refed a high carbohydrate diet. In contrast, a high fat carbohydrate-free diet does not increase G6PD mRNA and dibutyryl cAMP lowers G6PD mRNA. Since changes in G6PD synthesis and activity are closely correlated, degradation of G6PD is not significantly regulated.

Animals↗
PubMed1988

Nucleotide sequence of the Drosophila glucose-6-phosphate dehydrogenase gene and comparison with the homologous human gene.

Glucose-6-phosphate dehydrogenase (G6PD) has a major role in NADPH production and is found in almost all cell types. The structural gene for G6PD is X-linked in Drosophila melanogaster, as it is in most eukaryotic organisms, and due to its ubiquitous expression, it can be considered a typical 'housekeeping' gene. Here we present the complete nucleotide (nt) sequence of G6PD cDNAs as well as the genomic copy of the G6PD gene. The G6PD gene has three introns so that the protein-coding region is divided into four segments. The 5'-end of mature G6PD mRNA is located 289 +/- 1 nt upstream from the start codon. The sequence upstream from the transcription start point is G + T-rich and contains no commonly found transcription regulatory elements, such as a TATA box or GGGCGG sequence. D. melanogaster G6PD is 65% homologous with the human G6PD protein but has no homology with the human sequence for the first 42 amino acid residues. The G6PD gene was shown to be active when transduced to autosomal positions. For each transformant, G6PD activity in both male and female adults was not significantly different, indicating that the transduced gene, unlike the resident G6PD, is not dosage-compensated in males.

Amino Acid Sequence↗
PubMed2005

Rapid detection of glucose-6-phosphate dehydrogenase gene mutations by denaturing high-performance liquid chromatography.

OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited disorder worldwide. Different kinds of G6PD mutations may result in variable severity of clinical onset in G6PD-deficient individuals. In this study, a reliable molecular diagnostic method was developed for rapid detection of G6PD gene mutation. DESIGN AND METHODS: Primers were designed to amplify G6PD gene fragments that were subjected to mutation screening using denaturing high-performance liquid chromatography (DHPLC) analysis. Mutations were identified by their distinct elution peak patterns and were confirmed by DNA sequencing. The assay was further validated against 29 samples from individuals with G6PD deficiency. RESULTS: A DHPLC-based assay for G6PD mutation detection was established. The 9 common G6PD mutations in the Taiwanese and Chinese population could be distinguished through the analysis of DNA elution patterns. During the validation test with the 29 G6PD deficiency specimens, two additional rare mutations, T517C and C519G, were unveiled. Overall, the DHPLC-based mutation detection was 100% concordant with the DNA sequencing results. CONCLUSION: Compared to other genotyping techniques, this method requires significantly less technical time to perform and has a greatly increased throughput capacity. Hence, the DHPLC method represents a major technical advance for G6PD genotyping and should benefit G6PD-deficient individuals for proper clinical care.

Chromatography, High Pressure Liquid↗
PubMed2003

Hyperbilirubinemia in healthy neonates with glucose-6-phosphate dehydrogenase deficiency.

A cohort study was carried out to assess the association between glucose-6-phosphate dehydrogenase (G6PD) deficiency, diagnosed by quantitative enzyme assay, and neonatal hyperbilirubinemia, defined as serum total bilirubin >/=15 mg/dl, in the well-baby nursery of Chang Gung Children's Hospital. Among 42,110 inborn infants, 757 male (3.54%) and 326 female (1.57%) newborns were G6PD-deficient. Compared to the occurrence of hyperbilirubinemia in G6PD-normal newborns (1.41% in male, 1.44% in female) in the well-baby nursery, a significantly higher incidence was observed in both G6PD-deficient male (11.36%) and female (7.06%) newborns. Further analyses demonstrated that the enzyme activity of G6PD in G6PD-deficient male newborns with hyperbilirubinemia (1.56+/-1.37 U/g Hb) were significantly lower than the subjects without hyperbilirubinemia (2.01+/-1.7 U/g Hb). No significant difference was observed in G6PD-deficient female newborns with hyperbilirubinemia (6.91+/-2.76 U/g Hb) compared to those without hyperbilirubinemia (7.81+/-2.84 U/g Hb). These data suggest that the G6PD-deficient neonates are at increased risk for hyperbilirubinemia even in the nursery free from agents that can potentially cause hemolysis to G6PD-deficient red cells. The lower G6PD enzyme activity was associated with the neonatal hyperbilirubinemia in G6PD-deficient male neonates.

Cohort Studies↗
PubMed2002

Suppression of interleukin-1 beta-induced nitric oxide production in RINm5F cells by inhibition of glucose-6-phosphate dehydrogenase.

In rat pancreatic islets and insulin-producing cell lines, IL-1beta induces expression of inducible nitric oxide synthase and NO production leading to impairment of glucose-stimulated insulin release and decreased cell survival. NADPH is an obligatory cosubstrate for iNOS synthesis of NO. We hypothesized that IL-1beta stimulates an increase in activity of NADPH-producing enzyme(s) prior to NO production and that this increase is necessary for NO production. Using rat insulin-secreting RINm5F cells, we found that (1) IL-1beta caused a biphasic change in the NADPH level (increased by 6 h and decreased after prolonged incubation in the presence of 2 ng/mL IL-1beta); (2) IL-1beta stimulated increased activity of glucose-6-phosphate dehydrogenase (G6PD) in a time- and dose-dependent manner, and G6PD expression was increased by about 80% after exposure to 2 ng/mL IL-1beta for 18 h: (3) IL-1beta-stimulated NO production was positively correlated with increased G6PD activity; (4) IL-1beta did not cause any significant change in enzyme activity of another NADPH-producing enzyme, malic enzyme; (5) IL-1beta-induced NO production was significantly reduced either by inhibiting G6PD activity using an inhibitor of G6PD (dehydroepiandrosterone) or by inhibiting G6PD expression using an antisense oligonucleotide to G6PD mRNA; and (6) IL-1beta stimulated a decrease in the cAMP level. 8-Bromo-cAMP caused decreased G6PD activity, and the protein kinase A inhibitor H89 led to a increase in G6PD activity in RINm5F cells. In conclusion, our data show that IL-1beta stimulated G6PD activity and expression level, providing NADPH that is required by iNOS for NO production in RINm5F cells. Also, inhibition of the cAMP-dependent PKA signal pathway is involved in an IL-1beta-stimulated increase in G6PD activity.

Animals↗
PubMed2003

Failure to increase glucose consumption through the pentose-phosphate pathway results in the death of glucose-6-phosphate dehydrogenase gene-deleted mouse embryonic stem cells subjected to oxidative stress.

Mouse embryonic stem (ES) glucose-6-phosphate (G6P) dehydrogenase-deleted cells ( G6pd delta), obtained by transient Cre recombinase expression in a G6pd -loxed cell line, are unable to produce G6P dehydrogenase (G6PD) protein (EC 1.1.1.42). These G6pd delta cells proliferate in vitro without special requirements but are extremely sensitive to oxidative stress. Under normal growth conditions, ES G6pd delta cells show a high ratio of NADPH to NADP(+) and a normal intracellular level of GSH. In the presence of the thiol scavenger oxidant, azodicarboxylic acid bis[dimethylamide], at concentrations lethal for G6pd delta but not for wild-type ES cells, NADPH and GSH in G6pd delta cells dramatically shift to their oxidized forms. In contrast, wild-type ES cells are able to increase rapidly and intensely the activity of the pentose-phosphate pathway in response to the oxidant. This process, mediated by the [NADPH]/[NADP(+)] ratio, does not occur in G6pd delta cells. G6PD has been generally considered essential for providing NADPH-reducing power. We now find that other reactions provide the cell with a large fraction of NADPH under non-stress conditions, whereas G6PD is the only NADPH-producing enzyme activated in response to oxidative stress, which can act as a guardian of the cell redox potential. Moreover, bacterial G6PD can substitute for the human enzyme, strongly suggesting that a relatively simple mechanism of enzyme kinetics underlies this phenomenon.

Animals↗
PubMed2005

Alphab-crystallin-assisted reactivation of glucose-6-phosphate dehydrogenase upon refolding.

Alphab-crystallin, a small heat-shock protein has been shown to prevent the aggregation of other proteins under various stress conditions. We have investigated the role of alphaB-crystallin in the reactivation of denaturant [GdmCl (guanidinium chloride)]-inactivated G6PD (glucose-6-phosphate dehydrogenase). Studies indicate that unfolding and inactivation of G6PD by GdmCl proceeds via formation of a molten globule-like state at low concentrations of GdmCl, which was characterized by having maximum surface hydrophobicity and no catalytic activity. At high concentrations of GdmCl, G6PD was completely unfolded, which upon dilution-induced refolding yielding 35% of original activity. In contrast, no activity was recovered when G6PD was refolded from a molten globule-like state. Interestingly, refolding of completely unfolded G6PD in the presence of alphaB-crystallin resulted in 70% gain of the original activity, indicating that alphaB-crystallin assisted in enhanced refolding of G6PD. Intriguingly, alphaB-crystallin was unable to reactivate G6PD from a molten globule-like state. Size-exclusion chromatography data indicate that alphaB-crystallin-assisted reactivation of completely unfolded G6PD is concomitant with the restoration of the native structure of G6PD. Nonetheless, alphaB-crystallin failed to reactivate G6PD from preformed aggregates. Moreover, methylglyoxal-modified alpha-crystallin, which occurs in aged and diabetic cataract lenses, was less efficient in the reactivation of denaturant inactivated G6PD. Diminished chaperone-like activity of alpha-crystallin due to post-translational modifications may thus result in the accumulation of aggregated/inactivated proteins.

Animals↗
PubMed2002

Cell growth and cholesterol metabolism in human glucose-6-phosphate dehydrogenase deficient lymphomononuclear cells.

Atherosclerosis is an inflammatory-fibroproliferative response of the arterial wall involving a complex set of interconnected events where cell proliferation (lymphomonocytes, and endothelial and smooth-muscle cells) and substantial perturbations of intracellular cholesterol metabolism are considered to be among the main features. Glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose-monophosphate shunt pathway, is an essential enzyme involved in both cell growth and cholesterol metabolism, raising the question as to whether G6PD deficiency may have metabolic and growth implications in a deficient population. In the present study, we investigated cell growth and cholesterol metabolism in peripheral blood lymphomononuclear cells (PBMC) from G6PD-normal (n = 5) and -deficient (n = 5) subjects stimulated with lectins (phytohaemoagglutinin and Concanavalin A). G6PD activity, DNA ([3H]-thymidine incorporation) cholesterol synthesis and esterification ([14C]-acetate and [14C]-oleate incorporation), and G6PD, HMGCoA reductase and low density lipoprotein (LDL) receptor mRNA levels (RT-PCR) all increased following lectin stimulation in both normal and G6PD-deficient cells. However, these parameters were significantly lower in G6PD-deficient cells (P < 0.05). It is of interest that G6PD-deficient PBMC, which showed lower expression of G6PD and higher expression of the LDL receptor gene than normal PBMC under basal conditions, exhibited an opposite pattern after stimulation: G6PD and HMGCoA reductase being expressed at significantly higher levels in deficient than in normal cells (P < 0.05). We conclude that the reduced capability of G6PD-deficient cells to respond to mitogenic stimuli and to synthesize cholesterol esters may represent favourable conditions for reducing the risk of cardiovascular diseases.

Adult↗
PubMed2002

Inhibition of the splicing of glucose-6-phosphate dehydrogenase precursor mRNA by polyunsaturated fatty acids.

Polyunsaturated fatty acids inhibit the expression of hepatic glucose-6-phosphate dehydrogenase (G6PD) by changes in the amount of G6PD pre-mRNA in the nucleus in the absence of changes in the transcription rate of the gene. We have compared the nuclear accumulation of partially and fully spliced mRNA for G6PD in the livers of mice fed diets high versus low in polyunsaturated fat. Consumption of a diet high in polyunsaturated fat decreased the accumulation of partially spliced forms of the G6PD pre-mRNA. Examining the fate of multiple introns within the G6PD primary transcript indicated that in mice fed a high fat diet, G6PD pre-mRNA containing intron 11 accumulated within the nucleus, whereas G6PD mature mRNA abundance was inhibited 50% or more within the same livers. Transient transfection of RNA reporters into primary hepatocyte cultures was used to localize the cis-acting RNA element involved in this regulated splicing. Reporter RNA produced from constructs containing exon 12 were decreased in amount by arachidonic acid. The extent of this decrease paralleled that seen in the expression of the endogenous G6PD mRNA. The presence of both exon 12 and a neighboring intron within the G6PD reporter RNA was essential for regulation by polyunsaturated fatty acid. Inhibition was not dependent on the presence of the G6PD polyadenylation signal and the 3'-untranslated region, but substitution with the SV40 poly(A) signal attenuated the inhibition by arachidonic acid. Thus, exon 12 contains a putative splicing regulatory element involved in the inhibition of G6PD expression by polyunsaturated fat.

Animals↗
PubMed2005

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.

Bilirubin↗
PubMed2004

Glucose-6-phosphate dehydrogenase activity in male premature and term neonates.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is higher in term neonates than in adults. Some studies have suggested that activity may be even higher in preterm infants. OBJECTIVES: To determine if G6PD activity is higher in preterm than term neonates, and whether higher activity would interfere with diagnosis of G6PD deficiency in premature infants. METHODS: G6PD activity was determined in the first 48 hours after delivery in male premature, term, and near term infants. G6PD deficient neonates were separated, and the remaining premature infants compared with healthy, male, G6PD normal, near term and term neonates. RESULTS: Ninety four premature infants (mean (SD) gestational age 31.9 (3.8) weeks (range 23-36)) were studied. In four, G6PD activity was 0.8-1.8 U/g haemoglobin (Hb), which is clearly in the deficient range with no overlap into the normal range. G6PD activity in the remaining premature infants was significantly higher than in 24 near term and term neonates (gestational age > or = 37 weeks) (14.2 (4.6) v 12.0 (3.8) U/g Hb). Further analysis showed that significance was limited to those born between 29 and 32 weeks gestation, in which group G6PD activity was significantly higher than in those born before 29 weeks gestation, at 33-36 weeks gestation, and > or = 37 weeks gestation. CONCLUSIONS: G6PD activity is higher in premature infants born between 29 and 32 weeks gestation than in term neonates. This did not interfere with diagnosis of G6PD deficiency.

Gestational Age↗
PubMed2005

Diabetes causes inhibition of glucose-6-phosphate dehydrogenase via activation of PKA, which contributes to oxidative stress in rat kidney cortex.

The incidence of diabetic nephropathy has been increasing. Studies have shown that oxidative stress (due to increased oxidant production and/or decreased antioxidant activity) is a critical underlying mechanism. The principal intracellular reductant is NADPH whose production is mainly dependent on glucose-6-phosphate dehydrogenase (G6PD) activity. Our work in cultured cells previously showed that high glucose caused activation of protein kinase A (PKA) and subsequent phosphorylation and inhibition of G6PD activity and hence decreased NADPH (Zhang Z, Apse K, Pang J, and Stanton RC. J Biol Chem 275:40042-40047, 2000). The purpose of this study was to determine whether these findings occur in diabetic rats (induced by streptozotocin) compared with control. G6PD activity and accordingly NADPH levels and glutathione levels were significantly decreased in diabetic kidneys compared with control kidneys. Lipid peroxidation was significantly increased, which correlated with decreased G6PD activity (r = 0.48). G6PD expression was significantly reduced, which correlated with decreased G6PD activity (r = 0.72). PKA activity and serine phosphorylation of G6PD were significantly increased and were closely correlated with decreased G6PD activity (r = 0.51 for PKA activity; r = 0.93 for serine phosphorylation of G6PD). Insulin treatment and/or correction of hyperglycemia ameliorated the changes caused by diabetes. In conclusion, chronic hyperglycemia caused inhibition of G6PD activity via decreased expression and increased phosphorylation of G6PD, which therefore led to increased oxidative stress.

Animals↗