Glucose-6-phosphate Dehydrogenase Deficiency and Malaria: Cytochemical Detection of Heterozygous G6PD Deficiency in Women

Peters, Anna; Noorden, C. J. F. Van

doi:10.1369/jhc.2009.953828

Cited by 124 publications

(135 citation statements)

References 54 publications

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“…To compensate for the decreased activity, an increased G6PD transcription is found in nucleus-containing cells. As erythrocytes lack a nucleus, these cells are not capable of increasing their G6PD content and are therefore highly affected by G6PD deficiency (21).…”

Section: G6pd Deficiencymentioning

confidence: 99%

Glucose‐6‐phosphate metabolism in Plasmodium falciparum

2012

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Malaria is still one of the most threatening diseases worldwide. The high drug resistance rates of malarial parasites make its eradication difficult and furthermore necessitate the development of new antimalarial drugs. Plasmodium falciparum is responsible for severe malaria and therefore of special interest with regard to drug development. Plasmodium parasites are highly dependent on glucose and very sensitive to oxidative stress; two observations that drew interest to the pentose phosphate pathway (PPP) with its key enzyme glucose‐6‐phosphate dehydrogenase (G6PD). A central position of the PPP for malaria parasites is supported by the fact that human G6PD deficiency protects to a certain degree from malaria infections. Plasmodium parasites and the human host possess a complete PPP, both of which seem to be important for the parasites. Interestingly, there are major differences between parasite and human G6PD, making the enzyme of Plasmodium a promising target for antimalarial drug design. This review gives an overview of the current state of research on glucose‐6‐phosphate metabolism in P. falciparum and its impact on malaria infections. Moreover, the unique characteristics of the enzyme G6PD in P. falciparum are discussed, upon which its current status as promising target for drug development is based. © 2012 IUBMB IUBMB Life, 64(7): 603–611, 2012

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Section: G6pd Deficiencymentioning

confidence: 99%

Glucose‐6‐phosphate metabolism in Plasmodium falciparum

2012

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“…Cytochemical staining of red blood cells followed by observation with either microscopy or flow cytometry represents the only way to observe the mosaic red blood cell population in heterozygous females 11, 12, 13, 14, 15, 16, 17. Cytofluorometric assays represent an opportunity to determine the relative G6PD activity at the level of the individual red blood cell.…”

Section: Introductionmentioning

confidence: 99%

Cytochemical flow analysis of intracellular G6PD and aggregate analysis of mosaic G6PD expression

Kalnoky

Bancone

Kahn

et al. 2018

European J of Haematology

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BackgroundMedicines that exert oxidative pressure on red blood cells (RBC) can cause severe hemolysis in patients with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency. Due to X‐chromosome inactivation, females heterozygous for G6PD with 1 allele encoding a G6PD‐deficient protein and the other a normal protein produce 2 RBC populations each expressing exclusively 1 allele. The G6PD mosaic is not captured with routine G6PD tests.MethodsAn open‐source software tool for G6PD cytofluorometric data interpretation is described. The tool interprets data in terms of % bright RBC, or cells with normal G6PD activity in specimens collected from 2 geographically and ethnically distinct populations, an African American cohort (USA) and a Karen and Burman ethnic cohort (Thailand) comprising 242 specimens including 89 heterozygous females.ResultsThe tool allowed comparison of data across 2 laboratories and both populations. Hemizygous normal or deficient males and homozygous normal or deficient females cluster at narrow % bright cells with mean values of 96%, or 6% (males) and 97%, or 2% (females), respectively. Heterozygous females show a distribution of 10‐85% bright cells and a mean of 50%. The distributions are associated with the severity of the G6PD mutation.ConclusionsConsistent cytofluorometric G6PD analysis facilitates interlaboratory comparison of cellular G6PD profiles and contributes to understanding primaquine‐associated hemolytic risk.

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“…These techniques are expensive, and need to be performed under good laboratory conditions by qualifi ed technicians, which end to restrict access to these tests. The fl uorescent spot test, the rapid screening test preconized from the World Health Organization (WHO), is able to identify severe defi ciency, but has decreased sensitivity in cases of mild-and low-defi ciency phenotypes (12) (13) (17) . To solve such problems, some point-of-care tests have emerged for screening G6PDd individuals.…”

Section: Introductionmentioning

confidence: 99%