Glucose-6-Phosphate Dehydrogenase Deficiency in Sickle-Cell Anemia

Steinberg, Martin H.; Dreiling, Bernard J.

doi:10.7326/0003-4819-80-2-217

Cited by 29 publications

(26 citation statements)

References 6 publications

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“…Thus no significant difference was found in the bilirubin levels in sickle cell patients with and without G6PD deficiency. It was consistent with the findings of Gibbs WN et al, Steinberg MH et al and Talafih K et al 4,5,20 Nouraie M et al observed that the G6PD deficiency was not associated with increased hemolysis as measured by lactate dehydrogenase, serum bilirubin, aspartate amino transferase or a haemolytic component derived from these markers (P > 0.09) and concluded that G6PD deficiency may be associated with lower hemoglobin concentration in sickle cell anemia by a mechanism other than increased hemolysis which was consistent with the present study. 13 However, Smits HL et al demonstrated increased jaundice as a result of accelerated hemolysis.…”

Section: Serum Bilirubinsupporting

confidence: 82%

“…[4][5][6]10,16 However the findings in the present study were contradictory to those of Carson and Frischer, Smits HL et al and Bouanga et al, in that a young red cell population associated with the sickle cell gene leading to elevated G6PD levels in G6PD deficient males suggests that sickle haemoglobin may exert a beneficial effect on G6PD deficiency, rather than the reverse. 1,7,17 These red cells may be better able to deal with oxidative stress (infection alone, drug alone, or a combination of both), which can precipitate severe haemolytic disease in G6PD deficiency.…”

Section: Severity Of Anemiacontrasting

confidence: 57%

“…et al, Steinberg MH et al and Saad STO et al too did not find any statistically significant difference in the reticulocyte count in sickle cell patients with and without G6PD deficiency. [4][5][6] Smits HL et al demonstrated a brisk reticulocytosis in patients with sickle cell disease and G6PD deficiency which was due to concurrent infection or administration of certain drugs known to cause hemolysis in G6PD deficient patients.…”

Section: Reticulocyte Countmentioning

confidence: 99%

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Influence of glucose-6 phosphate dehydrogenase (G6-PD) deficiency upon clinico-haematological and biochemical expression of patients with sickle cell disease

et al. 2017

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Background: According to world health organization, G6PD deficiency constitute 7.5% of world population as carriers whereas 2.9% as deficient. It has been reported from India that the prevalence varies from 0-27% in different caste, ethnic and linguistic groups. Various studies have revealed strong interaction between G6PD deficiency and sickle cell genes on one hand and environment on the other, one may therefore expect changes in their frequencies over a period of time in the population. We studied the influence of G6PD deficiency upon the clinico-haematological and biochemical expression of sickle cell disease.

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Section: Serum Bilirubinsupporting

confidence: 82%

Section: Severity Of Anemiacontrasting

confidence: 57%

Section: Reticulocyte Countmentioning

confidence: 99%

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Influence of glucose-6 phosphate dehydrogenase (G6-PD) deficiency upon clinico-haematological and biochemical expression of patients with sickle cell disease

et al. 2017

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“…43 In light of our present findings, however, phenotype penetrance of G6PD deficiency in SCA is likely to be limited in the setting of HMP constraint arising from HbS-cdB3 interactions (eg, G6P substrate lack might render G6PD deficiency moot; see Figure 7). Therefore, by varying G6P availability, it may be more likely that EMP (rather than HMP) enzymopathies or variations in activity (with polymorphism) will influence the impact of dysfunctional cdB3 masking by HbS.…”

Section: Discussionmentioning

confidence: 73%

Sickle hemoglobin disturbs normal coupling among erythrocyte O2 content, glycolysis, and antioxidant capacity

Rogers¹,

Ross²,

Davignon

et al. 2013

Blood

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Key Points• Hb-conformation-dependent interaction with band 3 protein regulates glycolysis in RBCs.• In hypoxia, HbS disrupts this system, disabling RBC antioxidant defense. Energy metabolism in RBCs is characterized by O 2 -responsive variations in flux through the Embden Meyerhof pathway (EMP) or the hexose monophosphate pathway (HMP). Therefore, the generation of ATP, NADH, and 2,3-DPG (EMP) or NADPH (HMP) shift with RBC O 2 content because of competition between deoxyhemoglobin and key EMP enzymes for binding to the cytoplasmic domain of the Band 3 membrane protein (cdB3). Enzyme inactivation by cdB3 sequestration in oxygenated RBCs favors HMP flux and NADPH generation (maximizing glutathione-based antioxidant systems). We tested the hypothesis that sickle hemoglobin disrupts cdB3-based regulatory protein complex assembly, creating vulnerability to oxidative stress. In RBCs from patients with sickle cell anemia, we demonstrate in the present study constrained HMP flux, NADPH, and glutathione recycling and reduced resilience to oxidative stress manifested by membrane protein oxidation and membrane fragility. Using a novel, inverted membrane-on-bead model, we illustrate abnormal (O 2 -dependent) association of sickle hemoglobin to RBC membrane that interferes with sequestration/inactivation of the EMP enzyme GAPDH. This finding was confirmed by immunofluorescent imaging during RBC O IntroductionSickle cell anemia (SCA) arises from a single amino acid substitution (Glu6Val) in the ␤-globin chain. Although the change to hemoglobin (Hb) is simple and uniform, SCA is characterized by broad differences in clinical manifestation. Phenotype variation in SCA is thought to arise from both environmental and genetic factors (eg, ␤-gene cluster haplotype, degree of HbF expression, or effects of other epistatic genes). The environmental factor that most clearly influences SCA phenotype is hypoxia, which drives sickle Hb (HbS) polymerization and the resulting well-characterized alterations in RBC physiology and the microcirculation. However, the influence of hypoxia on the SCA phenotype appears to be insufficiently explained by HbS polymerization alone. 1 Moreover, we lack a clear mechanistic understanding of the significant oxidative stress complicating SCA, a key feature of phenotype variation, both at rest and in association with hypoxia. 2 Nonpolymerized, solution-phase HbS may promote oxidative stress, even in RBCs under normal physiologic O 2 gradients. 3 Specifically, the low redox potential for heme in HbS 4 and avid binding affinity of HbS for the cytoplasmic regulatory domain of the Band 3 membrane protein (cdB3) 5,6 strongly affect RBC energetics and antioxidant systems [7][8][9] and, notably, do so as a function of RBC O 2 content. Therefore, both the genesis and the disposal of reactive oxygen species are abnormal in SCA, creating a baseline state of oxidative stress, which worsens in hypoxia.In particular, consideration of metabolic control in RBCs suggests O 2 -dependent HbS-cdB3 interaction as a relatively ...

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“…For some families, it may be appropriate to offer hemoglobin electrophoresis, IEF, or HPLC and/or CBC, blood smear, and reticulocyte counts on parents. Infants with clinical or laboratory evidence of hemolysis or abnormal oxygen affinity and those without Hb A, especially compound heterozygotes with Hb S, require definitive hemoglobin identification (21,36,37). This may require protein sequencing, DNA analysis, or HPLC combined with electrospray mass spectrometry in a specialized reference laboratory (38).…”

Section: Unidentified Hemoglobin Variantsmentioning

confidence: 99%

Commentary on “Adolescents With Sickle Cell Disease in a Rural Community: Are They Ready to Transition to Adulthood?”

Kreze¹

2014

Southern Medical Journal

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Glucose-6-Phosphate Dehydrogenase Deficiency in Sickle-Cell Anemia

Cited by 29 publications

References 6 publications

Influence of glucose-6 phosphate dehydrogenase (G6-PD) deficiency upon clinico-haematological and biochemical expression of patients with sickle cell disease

Influence of glucose-6 phosphate dehydrogenase (G6-PD) deficiency upon clinico-haematological and biochemical expression of patients with sickle cell disease

Sickle hemoglobin disturbs normal coupling among erythrocyte O2 content, glycolysis, and antioxidant capacity

Commentary on “Adolescents With Sickle Cell Disease in a Rural Community: Are They Ready to Transition to Adulthood?”

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