PharmGKB summary

McDonagh, Ellen M.; Thorn, Caroline F.; Bautista, José M.; Youngster, Ilan; Altman, Russ B.; Klein, Teri E.

doi:10.1097/fpc.0b013e32834eb313

Cited by 43 publications

(18 citation statements)

References 99 publications

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“…It is an X-linked disorder with a varying clinical presentation depending on the extent of the inactivation of the affected X chromosome bearing the abnormal gene. Worldwide, more than 300 variants of G6PD deficiency have been described and are categorized by the WHO according to the extent of enzyme deficiency and severity of hemolysis [6]. For example, the G6PD A(-) variant is present in 10-15% of African American males and represents an unstable variant, resulting in a decrease in enzyme activity in aged RBCs.…”

Section: Discussionmentioning

confidence: 99%

Glucose-6-Phosphate Dehydrogenase Deficiency-Associated Hemolytic Anemia and Methemoglobinemia in a Patient Treated With Hydroxychloroquine in the Era of COVID-19

Laslett¹,

Hibbs²,

Hallett³

et al. 2021

Cureus

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells worldwide. The severity of hemolytic anemia varies among individuals with G6PD deficiency, depending on the genetic variant in the G6PD gene; this makes the diagnosis of the condition more challenging in some cases. In this report, we present a case of severe hemolytic anemia and methemoglobinemia in a patient with G6PD deficiency who had been exposed to hydroxychloroquine prescribed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To the best of our knowledge and based on a literature search, this is one of the first case reports in the literature about hemolytic crisis and methemoglobinemia in a patient with critical illness due to severe coronavirus disease 2019 (COVID-19) who was exposed to hydroxychloroquine. It is critical for physicians and caregivers to recognize the effects of oxidative stressors such as hydroxychloroquine, particularly in this era of the COVID-19 pandemic and in regions with a high prevalence of G6PD deficiency, for the appropriate management of this unique subset of patients.

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Section: Discussionmentioning

confidence: 99%

Glucose-6-Phosphate Dehydrogenase Deficiency-Associated Hemolytic Anemia and Methemoglobinemia in a Patient Treated With Hydroxychloroquine in the Era of COVID-19

Laslett¹,

Hibbs²,

Hallett³

et al. 2021

Cureus

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“…G6PD deficient RBCs are unable to enhance NADPH production and are thus more susceptible to oxidative damage that can ultimately result in methemoglobinemia and/or hemolysis [39, 43–49]. More than 180 genetic variants within the G6PD gene have been described to date, and many confer deficiency of the G6PD enzyme in RBCs (see the PharmGKB G6PD VIP summary for more detailed information www.pharmgkb.com/vip/PA28469) [44, 50–53]. Several cases of methemoglobinemia and hemolytic anemia subsequent to treatment by rasburicase or urate oxidase have been reported in G6PD deficient individuals, though the underlying G6PD variant is often not reported and few studies report genotyping (Table 2).…”

Section: ) Drugs That Increase the Removal Of Uric Acid: Urate Oxidamentioning

confidence: 99%

PharmGKB summary

McDonagh¹,

Thorn²,

Callaghan

et al. 2014

Pharmacogenetics and Genomics

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“…However, there are diverse hypothetical mechanisms which may result in prevention of viral entry into the cell, restriction of access to cell replication machinery, or by modulating the immunological response of the host (e.g cytokine storm) [ 2 – 4 ]. CQ/HCQ and other aminoquinolines have pharmacogenomic associations with the glucose-6-phosphate dehydrogenase ( G6PD ) gene [ 5 ]. Aminoquinolines are suspected to exert their antimalarial effect by increasing oxidative stress via production of haem-based reactive oxygen species [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Three common haplotype arrangements have been defined for the gene, the B (wild type), A, and A– (deficiency) all of which are defined by a combination of variants from the rs1050829 and rs1050828 loci [ 5 ]. The G6PD A ‘haplotype’ is denoted by the rs1050829 C variant (NM_001042351.2:c.376 A > G).…”

Section: Introductionmentioning

confidence: 99%

“…The A– haplotype (which is associated with G6PD enzyme deficiency) is formed by a combination of two variants, one of which is rs1050828 T (NM _001042351.2:c.202 G > A) (a deleterious variant), while the other is the rs1050829 C. This combination occurs in 10% of sub-Saharan Africans [ 5 ]. The A– G6PD haplotype is a World Health Organisation (WHO) Class III variant corresponding to a decrease from 10 to 60% of the normal enzyme activity [ 5 , 13 , 14 ]. Strong linkage disequilibrium exists between the rs1050828 T and rs1050829 C variants [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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G6PD distribution in sub-Saharan Africa and potential risks of using chloroquine/hydroxychloroquine based treatments for COVID-19

et al. 2021

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Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, p = 2.4 × 10−3). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydroxychloroquine for treatment of COVID-19 in Africans.

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PharmGKB summary

Cited by 43 publications

References 99 publications

Glucose-6-Phosphate Dehydrogenase Deficiency-Associated Hemolytic Anemia and Methemoglobinemia in a Patient Treated With Hydroxychloroquine in the Era of COVID-19

Glucose-6-Phosphate Dehydrogenase Deficiency-Associated Hemolytic Anemia and Methemoglobinemia in a Patient Treated With Hydroxychloroquine in the Era of COVID-19

PharmGKB summary

G6PD distribution in sub-Saharan Africa and potential risks of using chloroquine/hydroxychloroquine based treatments for COVID-19

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