Effects of glucose-6-phosphate dehydrogenase deficiency upon sickle cell anemia

We studied the interactions of the A- variety of glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell anemia (HbSS) to see if G6PD deficiency influenced laboratory and clinical features of HbSS. A total of 801 male patients over age 2 had G6PD electrophoresis on cellulose acetate membranes. Assays of both G6PD activity and hexokinase activity were then done on all samples that had an electrophoretic pattern other than the normal wild type (GdB). The collection of clinical data used a standardized protocol. Using cluster analyses we classified 10.4% males to be G6PD deficient, while 18.4% had the functionally normal GdA+ enzyme. The prevalence of G6PD deficiency did not change significantly when age was stratified by decade, suggesting little survival advantage or disadvantage of the combination of G6PD deficiency and HbSS. Compared to patients who were not G6PD deficient, there were no significant differences in the hemoglobin concentration, mean corpuscular volume, reticulocyte count, bilirubin, or SGOT level in patients with HbSS who had G6PD deficiency. The incidence of painful episodes, sepsis, or acute anemic episodes was similar in both groups. Our results are consistent with recent studies of smaller numbers of patients that have found little influence of G6PD deficiency upon HbSS. Specifically, we found no evidence that G6PD enhanced the severity of hemolysis or increased the incidence of acute anemic episodes or sepsis in HbSS.

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Effects of glucose-6-phosphate dehydrogenase deficiency upon sickle cell anemia

Blood ◽

10.1182/blood.v71.3.748.748 ◽

1988 ◽

Vol 71 (3) ◽

pp. 748-752 ◽

Cited By ~ 40

Author(s):

MH Steinberg ◽

MS West ◽

D Gallagher ◽

W Mentzer

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

G6pd Deficiency ◽

Electrophoretic Pattern ◽

Hemoglobin Concentration ◽

Wild Type ◽

Standardized Protocol ◽

Cellulose Acetate Membranes ◽

Male Patients ◽

Glucose 6 Phosphate Dehydrogenase

Abstract We studied the interactions of the A- variety of glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell anemia (HbSS) to see if G6PD deficiency influenced laboratory and clinical features of HbSS. A total of 801 male patients over age 2 had G6PD electrophoresis on cellulose acetate membranes. Assays of both G6PD activity and hexokinase activity were then done on all samples that had an electrophoretic pattern other than the normal wild type (GdB). The collection of clinical data used a standardized protocol. Using cluster analyses we classified 10.4% males to be G6PD deficient, while 18.4% had the functionally normal GdA+ enzyme. The prevalence of G6PD deficiency did not change significantly when age was stratified by decade, suggesting little survival advantage or disadvantage of the combination of G6PD deficiency and HbSS. Compared to patients who were not G6PD deficient, there were no significant differences in the hemoglobin concentration, mean corpuscular volume, reticulocyte count, bilirubin, or SGOT level in patients with HbSS who had G6PD deficiency. The incidence of painful episodes, sepsis, or acute anemic episodes was similar in both groups. Our results are consistent with recent studies of smaller numbers of patients that have found little influence of G6PD deficiency upon HbSS. Specifically, we found no evidence that G6PD enhanced the severity of hemolysis or increased the incidence of acute anemic episodes or sepsis in HbSS.

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Glucose 6-phosphate dehydrogenase deficiency and sickle cell anemia: frequency and features of the association in an African community

Blood ◽

10.1182/blood.v46.4.591.591 ◽

1975 ◽

Vol 46 (4) ◽

pp. 591-597 ◽

Cited By ~ 30

Author(s):

U Bienzle ◽

O Sodeinde ◽

CE Effiong ◽

L Luzzatto

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Dehydrogenase Deficiency ◽

Clinical Course ◽

Normal Subjects ◽

Starch Gel Electrophoresis ◽

African Community ◽

Starch Gel ◽

Male Patients ◽

Glucose 6 Phosphate Dehydrogenase

Abstract The glucose 6-phosphate dehydrogenase (G6PD) genotype was determined in 100 male patients with homozygous sickle cell anemia (SS) by a combination of quantitative assay, cytochemical testing, and starch-gel electrophoresis. Of the 100 patients tested, 16 were found to be G6PD deficient (GdA-), AND 84 G6PD normal (22GsA and 62 GdB). This distribution of G6PD genotypes did not differ significantly from that observed in the general population. The level of G6PD activity in GdA- SS patients was nearly always higher than in G6PD-deficient subjects who did not have an associated hemolytic state, but it was nearly always lower than in G6PD-normal subjects. The clinical course of sickle cell disease, including the degree of anemia, was not milder in GdA- than in G6PD-normal patients but could not be proved to be significantly more severe. It was concluded that in this community the incidence of G6PD deficiency in sickle cell anemia was not greater than would be expected by chance, and there was no evidence that the coexistence of the GdA- gene in SS patients ameliorated their disease.

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Glucose 6-phosphate dehydrogenase deficiency and sickle cell anemia: frequency and features of the association in an African community

Blood ◽

10.1182/blood.v46.4.591.bloodjournal464591 ◽

1975 ◽

Vol 46 (4) ◽

pp. 591-597

Author(s):

U Bienzle ◽

O Sodeinde ◽

CE Effiong ◽

L Luzzatto

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Dehydrogenase Deficiency ◽

Clinical Course ◽

Normal Subjects ◽

Starch Gel Electrophoresis ◽

African Community ◽

Starch Gel ◽

Male Patients ◽

Glucose 6 Phosphate Dehydrogenase

The glucose 6-phosphate dehydrogenase (G6PD) genotype was determined in 100 male patients with homozygous sickle cell anemia (SS) by a combination of quantitative assay, cytochemical testing, and starch-gel electrophoresis. Of the 100 patients tested, 16 were found to be G6PD deficient (GdA-), AND 84 G6PD normal (22GsA and 62 GdB). This distribution of G6PD genotypes did not differ significantly from that observed in the general population. The level of G6PD activity in GdA- SS patients was nearly always higher than in G6PD-deficient subjects who did not have an associated hemolytic state, but it was nearly always lower than in G6PD-normal subjects. The clinical course of sickle cell disease, including the degree of anemia, was not milder in GdA- than in G6PD-normal patients but could not be proved to be significantly more severe. It was concluded that in this community the incidence of G6PD deficiency in sickle cell anemia was not greater than would be expected by chance, and there was no evidence that the coexistence of the GdA- gene in SS patients ameliorated their disease.

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Glucose 6 phosphate dehydrogenase deficiency and hemoglobinopathy in South Western Region Nepal: a boon or burden

BMC Research Notes ◽

10.1186/s13104-019-4762-6 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Narayan Gautam ◽

Bhagwati Gaire ◽

Trishna Manandhar ◽

Bishnu P. Marasini ◽

Niranjan Parajuli ◽

...

Keyword(s):

Sickle Cell ◽

G6pd Deficiency ◽

Sickle Cell Trait ◽

Amplification Refractory Mutation System ◽

Cellulose Acetate Electrophoresis ◽

Positive Trait ◽

Arms Pcr ◽

Phenotypic Method ◽

Mutation System ◽

Glucose 6 Phosphate Dehydrogenase

Abstract Objectives The study was carried out to optimize the phenotypic method to characterize the sickle cell trait (SCT), sickle cell anemia (SCA), and β-thalassemia (β-TT) suspected sample from tharu community of South Western province-5, Nepal. SCT and SCA were further evaluated by genotypic method employing amplification refractory mutation system (ARMS PCR). Moreover, Glucose 6 phosphate dehydrogenase (G6PD) was estimated in those hemoglobinopathy to observe its prevalence. The accurate and reliable method can play an important role in reduction of morbidity and mortality rate. Results The 100 suspected cases were subjected to phenotypic method adopting cellulose acetate electrophoresis and genotypic method using ARMS PCR which portraits (5%) SCA positive test showing HBS/HBS, (38%) SCT positive trait HBA/HBS and (36%) cases normal HBA/HBA. β-TT (21%) cases were confirmed by electropherogram. G6PD deficiency was observed in (40%) of SCA, (18.4%) of SCT, (4.8%) of β-TT and (2.8%) in normal cases. Increased G6PD were developed only in SCT (5.3%) and β-TT (4.8%). The study highlighted sickle cell disorder (SCD) and β-TT as the most common hemoglobinopathy coexisting with G6PD deficiency. Though hemoglobinopathy sometime could be protective in malaria but G6PD deficiency can cause massive hemolysis which may exacerbate the condition.

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Hematological and Genetic Predictors of Daytime Hemoglobin Saturation in Tanzanian Children with and without Sickle Cell Anemia

ISRN Hematology ◽

10.1155/2013/472909 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

Sharon E. Cox ◽

Julie Makani ◽

Charles R. Newton ◽

Andrew M. Prentice ◽

Fenella J. Kirkham

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Clinical Chemistry ◽

Pearson Correlation ◽

Transferrin Saturation ◽

Full Blood Count ◽

Hemoglobin F ◽

Hemoglobin Saturation ◽

Highly Correlated ◽

Glucose 6 Phosphate Dehydrogenase

Low hemoglobin oxygen saturation (SpO2) is common in Sickle Cell Anemia (SCA) and associated with complications including stroke, although determinants remain unknown. We investigated potential hematological, genetic, and nutritional predictors of daytime SpO2 in Tanzanian children with SCA and compared them with non-SCA controls. Steady-state resting pulse oximetry, full blood count, transferrin saturation, and clinical chemistry were measured. Median daytime SpO2 was 97% (IQ range 94–99%) in SCA (N = 458), lower () than non-SCA (median 99%, IQ range 98–100%; N = 394). Within SCA, associations with SpO2 were observed for hematological variables, transferrin saturation, body-mass-index z-score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability (, Adj ). In non-SCA only age correlated with SpO2. -thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient 0.60, ). In multivariable models, lower SpO2 correlated with higher MCH (-coefficient 0.32, ) or with decreased copies of -thalassemia 3.7 deletion (-coefficient 1.1, ), and independently in both models with lower HbF% (-coefficient 0.15, ) and Glucose-6-Phosphate Dehydrogenase genotype (-coefficient 1.12, ). This study provides evidence to support the hypothesis that effects on red cell rheology are important in determining SpO2 in children with SCA. Potential mechanisms and implications are discussed.

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Comorbidity of Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle Cell Disease Exert Significant Effect on RBC Indices

Anemia ◽

10.1155/2019/3179173 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Samuel Antwi-Baffour ◽

Jonathan Kofi Adjei ◽

Peter Owadee Forson ◽

Stephen Akakpo ◽

Ransford Kyeremeh ◽

...

Keyword(s):

Sickle Cell Disease ◽

Red Blood Cells ◽

Sickle Cell ◽

Blood Cells ◽

G6pd Deficiency ◽

Pentose Phosphate ◽

Full Blood Count ◽

Cell Disease ◽

Blood Disorder ◽

Glucose 6 Phosphate Dehydrogenase

Background. Glucose-6-phosphate dehydrogenase (G6PD) converts glucose-6-phosphate into 6-phosphogluconate in the pentose phosphate pathway and protects red blood cells (RBCs) from oxidative damage. Their deficiency therefore makes RBCs prone to haemolysis. Sickle cell disease (SCD) on the other hand is a hereditary blood disorder in which there is a single nucleotide substitution in the codon for amino acid 6 substituting glutamic acid with valine. SCD patients are prone to haemolysis due to the shape of their red blood cells and if they are deficient in G6PD, the haemolysis may escalate. Reported studies have indicated variations in the prevalence of G6PD deficiency in SCD patients and as such further work is required. The aim of this study was therefore to estimate the incidence of G-6-PD deficiency among SCD patients and to determine its impact on their RBC parameters as a measure of incidence of anaemia.Methods. A total of 120 clinically diagnosed SCD patients of genotypes HbSS and HbSC were recruited into the study. About 5ml of blood was collected via venipuncture from each patient and used to run G6PD, full blood count, and haemoglobin (Hb) electrophoresis tests. The data were analyzed using SPSS version 20 and Graphpad prism.Result. G6PD deficiency was detected in 43 (35.83%) of the participants made up of 16 (13.33%) males and 27 (22.50%) females of whom 17 (14.17%) had partial deficiency and 10 (8.33%) full deficiency. Statiscally significant differences p=0.036 and p=0.038 were established between the Hb concentration of the participants having a G6PD deficiency and those with normal G6PD activity for males and females, respectively.Conclusion. From the results obtained, it implies that G6PD deficiency may increase the severity of anaemia in SCD patients. There is therefore the need to screen all SCD patients for G6PD deficiency to ensure that their condition is not exacerbated during treatment.

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Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia

Blood ◽

10.1182/blood-2007-08-110098 ◽

2008 ◽

Vol 111 (8) ◽

pp. 3991-3997 ◽

Cited By ~ 127

Author(s):

Kenneth I. Ataga ◽

Wally R. Smith ◽

Laura M. De Castro ◽

Paul Swerdlow ◽

Yogen Saunthararajah ◽

...

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Hemoglobin Concentration ◽

Hemoglobin Level ◽

Dose Finding ◽

High Dose ◽

Double Blind ◽

Point Change ◽

Indirect Bilirubin ◽

Gardos Channel

Abstract Senicapoc, a novel Gardos channel inhibitor, limits solute and water loss, thereby preserving sickle red blood cell (RBC) hydration. Because hemoglobin S polymerization is profoundly influenced by intracellular hemoglobin concentration, senicapoc could improve sickle RBC survival. In a 12-week, multicenter, phase 2, randomized, double-blind, dose-finding study, we evaluated senicapoc's safety and its effect on hemoglobin level and markers of RBC hemolysis in sickle cell anemia patients. The patients were randomized into 3 treatment arms: placebo; low-dose (6 mg/day) senicapoc; and high-dose (10 mg/day) senicapoc. For the primary efficacy end point (change in hemoglobin level from baseline), the mean response to high-dose senicapoc treatment exceeded placebo (6.8 g/L [0.68 g/dL] vs 0.1 g/L [0.01 g/dL], P < .001). Treatment with high-dose senicapoc also produced significant decreases in such secondary end points as percentage of dense RBCs (−2.41 vs −0.08, P < .001); reticulocytes (−4.12 vs −0.46, P < .001); lactate dehydrogenase (−121 U/L vs −15 U/L, P = .002); and indirect bilirubin (−1.18 mg/dL vs 0.12 mg/dL, P < .001). Finally, senicapoc was safe and well tolerated. The increased hemoglobin concentration and concomitant decrease in the total number of reticulocytes and various markers of RBC destruction following senicapoc administration suggests a possible increase in the survival of sickle RBCs. This study is registered at http://clinicaltrials.gov as NCT00040677.

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Sequence-Specific Conversion of βA- to βS-Globin by Small Fragment Homologous Replacement In Hematopoietic Stem/Progenitor Cells.

Blood ◽

10.1182/blood.v116.21.3754.3754 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3754-3754

Author(s):

Alireza Abdolmohammadi ◽

Rosalie Maurisse ◽

Babek Bedayat ◽

David DeSemir ◽

Damian Laber ◽

...

Keyword(s):

Progenitor Cells ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Dna Sequences ◽

Conflicts Of Interest ◽

Globin Gene ◽

Specific Gene ◽

Small Fragment ◽

Wild Type ◽

Hematopoietic Stem

Abstract Abstract 3754 Introduction: An ultimate goal of gene therapy is the development of effective strategies to correct mutant genomic sequences in pathologic cells. To that end, studies have been undertaken to evaluate the therapeutic potential of an oligo/polynucleotide-based sequence-specific gene modification strategy, small fragment homologous replacement (SFHR) in the correction of the mutation giving rise to sickle cell anemia. Small DNA fragments (SDFs) comprising the sickle cell anemia mutation (an A>T transversion in codon 6) and flanking DNA sequences in the human b-globin gene were introduced into Hematopoietic Stem/Progenitor Cells (HSPCs). The studies presented indicated modification at the level of DNA, RNA, and protein when cells were differentiated into erythrocytes. Methods: In this study, SFHR was used to convert A>T in codon 6 of the b-globin gene in CD34+/CD38-/Lin- HSPCs isolated from full term umbilical cord blood as a proof of principle. HSPCs were transfected with a defined number of a 559-bp SDF using the Amaxa electroporation (nucleofection) system. After growing the transfected cells in stem cell media containing EPO for different time intervals up to 32 days, RNA was extracted and DNase I-treated before further analysis. Erythrocytes were also analyzed using antibodies that differentiate between wild-type hemoglobin A (HBA) and sickle cell hemoglobin S (HBS). Results: RFLP analysis of a 430-bp PCR product generated from mRNA-derived cDNA with the DdeI enzyme indicated conversion of bA- to bS-globin. Sequencing of the 430-bp amplicon showed the A > T conversion. Analysis of the transfected wild-type HSPC-derived erythrocytes with HBA and HBS specific antibodies demonstrated the presence of a subpopulation of cells expressing HBS. These data are consistent with previous studies showing both conversion of bS- to bA-globin in SC1 cells and bA- to bS-globin in HSPCs after electroporation and microinjection of SDF, respectively. Conclusion: These studies represent a critical next step in developing SFHR as a therapy for sickle cell disease, in that they demonstrate long-term SFHR-mediated modification of b-globin following mass transfection by electroporation of HSPCs. Disclosures: No relevant conflicts of interest to declare.

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