Glucose-6-phosphate Dehydrogenase Deficiency: A Review
DOI:
https://doi.org/10.5195/ijms.2020.637Keywords:
Glucosephosphate dehydrogenase deficiency, Haemolytic anaemia, Neonatal jaundice, ErythrocytesAbstract
Deficiency of glucose-6-phosphate dehydrogenase enzyme is a common X-linked disorder that affects humans globally. It was first identified in the 1950s as a disorder that primarily affects the red blood cells causing a myriad of symptoms including acute haemolytic anaemia, neonatal jaundice and chronic nonspherocytic haemolytic anaemia. The deficiency has been extensively studied and especially in the last 5 years there have been improvements in the diagnosis and management. Various methods of diagnosis exist, however recent research focusses on the use of biosensors for more accurate and less time-consuming diagnosis. Guidelines suggest on controlling symptomology as there exists no specific treatment. Neonatal jaundice is a common complication of the disease and research on phototherapy has proved to show some effect in managing this condition. In the last year, protein-protein interactions have been studied and are used as a target to enhance enzyme stability and activity. AG1 is a small molecule activator that has demonstrated effectiveness in treating G6PD deficiency in models. The purpose of this review is to summarize existing literature and potential areas of research on glucose-6-phosphate dehydrogenase deficiency including clinical characteristics, diagnosis and management.
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References
1. National Organization for Rare Disorders. https://rarediseases. org/rare-diseases/glucose-6-phosphate-dehydrogenase-deficiency. Accessed June 1, 2020.
2. Lo, E., Zhong, D., Raya, B., Pestana, K., Koepfli, C., & Lee, M. C. (2019). Prevalence and distribution of G6PD deficiency: implication for the use of primaquine in malaria treatment in Ethiopia. Malaria Journal, 1–10. https://doi.org/10.1186/s12936-019-2981-x
3. Belfield, K. D., & Pharm, D. (2018). Review and drug therapy implications of glucose-6-phosphate dehydrogenase deficiency, 75(3), 97–104. https://doi.org/10.2146/ajhp160961
4. Lee, M. H., Malloy, C. R., Corbin, I. R., & Jin, E. S. (2019). Assessing the pentose phosphate pathway using [ 2 , 3 ? 13 C 2 ] glucose, (February), 1–10. https://doi.org/10.1002/nbm.4096
5. Mason, P. J., Bautista, M., & Gilsanz, F. (2007). G6PD deficiency: the genotype-phenotype association, 267–283. https://doi.org/10.1016/j.blre.2007.05.002
6. Drousiotou, A., Touma, E. H., Andreou, N., Loiselet, J., Angastiniotis, M., Verrelli, B. C., & Tishkoff, S. A. (2004). Molecular characterization of G6PD deficiency in Cyprus, 33, 25–30. https://doi.org/10.1016/j.bcmd.2004.03.004
7. Harcke, S. J., Rizzolo, D., & Harcke, H. T. (2019). G6PD deficiency: An update, 21–26. https://doi.org/10.1097/01.JAA.0000586304.65429.a7
8. Luzzatto, L., & Seneca, E. (n.d.). G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications. https://doi.org/10.1111/bjh.12665
9. Hecker, P. A., Leopold, J. A., Gupte, S. A., Recchia, F. A., & Stanley, W. C. (2020). Impact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease. https://doi.org/10.1152/ajpheart.00721.2012
10. Finley, D. S. (2008). Stuttering Priapism: Report of a Case, 2963–2966. https://doi.org/10.1111/j.1743-6109.2008.01007.x
11. Persico, M. G., Viglietto, G., Martini, G., Toniolo, D., Moscatelli, C., Dono, R., Luzzatto, L. (1986), Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5’ non-coding region. Nucleic Acids Research, 14(6), 2511–2522.
12. World Health Organization Working Group. Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bull World Health Organ 67: 601–611, 1989.
13. Naylor C.E., Rowland P., Basak A.K., Gover S., Mason P.J., Bautista J.M., Vuilliamy T.J., Luzzatto L., Adams, M. J. (1996). Glucose 6-Phosphate Dehydrogenase Mutations Causing Enzyme Deficiency in a Model of the Tertiary Structure of the Human Enzyme, 87(7), 2974–2982.
14. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371(9606):64?74. doi:10.1016/S0140-6736(08)60073-2
15. Roper, D., Layton, M., Rees, D., Lambert, C., Vulliamy, T., Salle, B. De, & Souza, C. D. (n.d.). Laboratory diagnosis of G6PD deficiency. A British Society for Haematology Guideline. https://doi.org/10.1111/bjh.16366
16. Takizawa T, Huang IY, Ikuta, T, Yoshida A, (1986). Human glucose-6-phosphate dehydrogenase: Primary structure and cDNA cloning, 83(June), 4157–4161.
17. Deficiency, G. P. D., Gonz, A., Vanoye-carlo, A., & Hern, B. (2017). Functional and Biochemical Analysis of. https://doi.org/10.3390/catal7050135
18. Doss CG, Alasmar DR, Bux DI, Sneha P, Bakhsh FD, Al?Azwani I, et al. Genetic epidemiology of glucose?6?phosphate dehydrogenase defi? ciency in the Arab World. Sci Rep. 2016;6:37284.
19. Sarker SK, Islam MT, Eckhoff G, Hossain MA, Qadri SK, Muraduzzaman AK, et al. Molecular analysis of glucose?6?phosphate dehydrogenase gene mutations in Bangladeshi Individuals. PLoS One. 2016;11:e0166977.
20. Beutler E. G6PD deficiency. Blood. 1994;84:3613–36.
21. Beijtler, E., & Valentine, W. N. (1979). International Committee for Standardization in Haematology?: Recommended Screening Test for Glucose-6-Phosphate Dehydrogenase ( G-6-PD ) Deficiency, 465–467.
22. Tantular, I. S., & Kawamoto, F. (2003). An improved, simple screening method for detection of glucose-6-phosphate dehydrogenase deficiency, 8(6), 569–574.
23. Bancone, G., Kalnoky, M., Chu, C. S., Chowwiwat, N., Malleret, B., Pornpimon, W., Nosten, F. (2017). The G6PD flow-cytometric assay is a reliable tool for diagnosis of G6PD deficiency in women and anaemic subjects, (August), 1–8. https://doi.org/10.1038/s41598-017-10045-2
24. Aysun Adan, Gu?nel Alizada, Yag?mur Kiraz, Yusuf Baran & Ayten Nalbant (2017) Flow cytometry: basic principles and applications, Critical Reviews in Biotechnology, 37:2, 163-176, DOI: 10.3109/07388551.2015.1128876
25. Bancone G, Gornsawun G, Chu CS, Porn P, Pal S, Bansil P, et al. (2018) Validation of the quantitative point-of-care CareStart biosensor for assessment of G6PD activity in venous blood. PLoS ONE 13(5): e0196716. https://doi.org/ 10.1371/journal.pone.0196716
26. Tracts, H., Ley, B., Alam, M. S., Donnell, J. J. O., Hossain, S., Kibria, M. G., … Richards, J. S. (2017). RESEARCH ARTICLE A Comparison of Three Quantitative Methods to Estimate G6PD Activity in the Chittagong, 1–13. https://doi.org/10.1371/journal.pone.0169930
27. Minucci, A., Gentile, L., Zuppi, C., Giardina, B., & Capoluongo, E. (2012). Clinica Chimica Acta. Clinica Chimica Acta, 413(11–12), 1018–1019. https://doi.org/10.1016/j.cca.2012.01.032
28. Ben-Joseph E.P. (2018) G6PD Deficiency, Available at: https://kidshealth.org/en/parents/g6pd.html (Accessed: 20th February 2020).
29. Tan, K. L. (2020). Phototherapy for Neonatal Jaundice in Erythrocyte Infants mean.
30. Stokowski, L. A. (2006). Fundamentals of phototherapy for neonatal jaundice. Advances in Neonatal Care: Official Journal of the National Association of Neonatal Nurses, 6(6), 303–312. https://doi.org/10.1016/j.adnc.2006.08.004
31. Itoh S., Okada H., Kuboi T., Kusaka, T. (2017). Phototherapy for neonatal hyperbilirubinemia, 959–966. https://doi.org/10.1111/ped.13332
32. Wickremasinghe, A. C., Kuzniewicz, M. W., & Grimes, B. A. (2015). Neonatal Phototherapy and Infantile Cancer, 137(6). https://doi.org/10.1542/peds.2015-1353
33. Newman, T. B., Wickremasinghe, A. C., & Walsh, E. M. (2015). Retrospective Cohort Study of Phototherapy and Childhood Cancer in Northern California, 137(6).
34. Ngoc Le, T., Reese, J. (2017). Bronze Baby Syndrome. The Journal of Pediatrics, 188, 301–301.e1. https://doi.org/10.1016/j.jpeds.2017.05.005
35. Kopelman AE, Brown RS, Odell GB. The “bronze” baby syndrome: a complication of phototherapy. J Pediatr 1972; 81:466-72.
36. Raub, A. G., Hwang, S., Horikoshi, N., Cunningham, A. D., Rahighi S., Wakatsuki S., Mochly-Rosen D. (2019). Small-Molecule Activators of Glucose-6-phosphate Dehydrogenase (G6PD) Bridging the Dimer Interface, 92618, 1321–1324. https://doi.org/10.1002/cmdc.201900341
37. Hwang, S., Mruk, K., Rahighi, S., Raub, A. G., Chen, C. H., Dorn, L. E., Horikoshi, N., Wakatsuki, S., Chen, J. K., & Mochly-Rosen, D. (2018). Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator. Nature communications, 9(1), 4045. https://doi.org/10.1038/s41467-018-06447-z
2. Lo, E., Zhong, D., Raya, B., Pestana, K., Koepfli, C., & Lee, M. C. (2019). Prevalence and distribution of G6PD deficiency: implication for the use of primaquine in malaria treatment in Ethiopia. Malaria Journal, 1–10. https://doi.org/10.1186/s12936-019-2981-x
3. Belfield, K. D., & Pharm, D. (2018). Review and drug therapy implications of glucose-6-phosphate dehydrogenase deficiency, 75(3), 97–104. https://doi.org/10.2146/ajhp160961
4. Lee, M. H., Malloy, C. R., Corbin, I. R., & Jin, E. S. (2019). Assessing the pentose phosphate pathway using [ 2 , 3 ? 13 C 2 ] glucose, (February), 1–10. https://doi.org/10.1002/nbm.4096
5. Mason, P. J., Bautista, M., & Gilsanz, F. (2007). G6PD deficiency: the genotype-phenotype association, 267–283. https://doi.org/10.1016/j.blre.2007.05.002
6. Drousiotou, A., Touma, E. H., Andreou, N., Loiselet, J., Angastiniotis, M., Verrelli, B. C., & Tishkoff, S. A. (2004). Molecular characterization of G6PD deficiency in Cyprus, 33, 25–30. https://doi.org/10.1016/j.bcmd.2004.03.004
7. Harcke, S. J., Rizzolo, D., & Harcke, H. T. (2019). G6PD deficiency: An update, 21–26. https://doi.org/10.1097/01.JAA.0000586304.65429.a7
8. Luzzatto, L., & Seneca, E. (n.d.). G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications. https://doi.org/10.1111/bjh.12665
9. Hecker, P. A., Leopold, J. A., Gupte, S. A., Recchia, F. A., & Stanley, W. C. (2020). Impact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease. https://doi.org/10.1152/ajpheart.00721.2012
10. Finley, D. S. (2008). Stuttering Priapism: Report of a Case, 2963–2966. https://doi.org/10.1111/j.1743-6109.2008.01007.x
11. Persico, M. G., Viglietto, G., Martini, G., Toniolo, D., Moscatelli, C., Dono, R., Luzzatto, L. (1986), Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5’ non-coding region. Nucleic Acids Research, 14(6), 2511–2522.
12. World Health Organization Working Group. Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bull World Health Organ 67: 601–611, 1989.
13. Naylor C.E., Rowland P., Basak A.K., Gover S., Mason P.J., Bautista J.M., Vuilliamy T.J., Luzzatto L., Adams, M. J. (1996). Glucose 6-Phosphate Dehydrogenase Mutations Causing Enzyme Deficiency in a Model of the Tertiary Structure of the Human Enzyme, 87(7), 2974–2982.
14. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371(9606):64?74. doi:10.1016/S0140-6736(08)60073-2
15. Roper, D., Layton, M., Rees, D., Lambert, C., Vulliamy, T., Salle, B. De, & Souza, C. D. (n.d.). Laboratory diagnosis of G6PD deficiency. A British Society for Haematology Guideline. https://doi.org/10.1111/bjh.16366
16. Takizawa T, Huang IY, Ikuta, T, Yoshida A, (1986). Human glucose-6-phosphate dehydrogenase: Primary structure and cDNA cloning, 83(June), 4157–4161.
17. Deficiency, G. P. D., Gonz, A., Vanoye-carlo, A., & Hern, B. (2017). Functional and Biochemical Analysis of. https://doi.org/10.3390/catal7050135
18. Doss CG, Alasmar DR, Bux DI, Sneha P, Bakhsh FD, Al?Azwani I, et al. Genetic epidemiology of glucose?6?phosphate dehydrogenase defi? ciency in the Arab World. Sci Rep. 2016;6:37284.
19. Sarker SK, Islam MT, Eckhoff G, Hossain MA, Qadri SK, Muraduzzaman AK, et al. Molecular analysis of glucose?6?phosphate dehydrogenase gene mutations in Bangladeshi Individuals. PLoS One. 2016;11:e0166977.
20. Beutler E. G6PD deficiency. Blood. 1994;84:3613–36.
21. Beijtler, E., & Valentine, W. N. (1979). International Committee for Standardization in Haematology?: Recommended Screening Test for Glucose-6-Phosphate Dehydrogenase ( G-6-PD ) Deficiency, 465–467.
22. Tantular, I. S., & Kawamoto, F. (2003). An improved, simple screening method for detection of glucose-6-phosphate dehydrogenase deficiency, 8(6), 569–574.
23. Bancone, G., Kalnoky, M., Chu, C. S., Chowwiwat, N., Malleret, B., Pornpimon, W., Nosten, F. (2017). The G6PD flow-cytometric assay is a reliable tool for diagnosis of G6PD deficiency in women and anaemic subjects, (August), 1–8. https://doi.org/10.1038/s41598-017-10045-2
24. Aysun Adan, Gu?nel Alizada, Yag?mur Kiraz, Yusuf Baran & Ayten Nalbant (2017) Flow cytometry: basic principles and applications, Critical Reviews in Biotechnology, 37:2, 163-176, DOI: 10.3109/07388551.2015.1128876
25. Bancone G, Gornsawun G, Chu CS, Porn P, Pal S, Bansil P, et al. (2018) Validation of the quantitative point-of-care CareStart biosensor for assessment of G6PD activity in venous blood. PLoS ONE 13(5): e0196716. https://doi.org/ 10.1371/journal.pone.0196716
26. Tracts, H., Ley, B., Alam, M. S., Donnell, J. J. O., Hossain, S., Kibria, M. G., … Richards, J. S. (2017). RESEARCH ARTICLE A Comparison of Three Quantitative Methods to Estimate G6PD Activity in the Chittagong, 1–13. https://doi.org/10.1371/journal.pone.0169930
27. Minucci, A., Gentile, L., Zuppi, C., Giardina, B., & Capoluongo, E. (2012). Clinica Chimica Acta. Clinica Chimica Acta, 413(11–12), 1018–1019. https://doi.org/10.1016/j.cca.2012.01.032
28. Ben-Joseph E.P. (2018) G6PD Deficiency, Available at: https://kidshealth.org/en/parents/g6pd.html (Accessed: 20th February 2020).
29. Tan, K. L. (2020). Phototherapy for Neonatal Jaundice in Erythrocyte Infants mean.
30. Stokowski, L. A. (2006). Fundamentals of phototherapy for neonatal jaundice. Advances in Neonatal Care: Official Journal of the National Association of Neonatal Nurses, 6(6), 303–312. https://doi.org/10.1016/j.adnc.2006.08.004
31. Itoh S., Okada H., Kuboi T., Kusaka, T. (2017). Phototherapy for neonatal hyperbilirubinemia, 959–966. https://doi.org/10.1111/ped.13332
32. Wickremasinghe, A. C., Kuzniewicz, M. W., & Grimes, B. A. (2015). Neonatal Phototherapy and Infantile Cancer, 137(6). https://doi.org/10.1542/peds.2015-1353
33. Newman, T. B., Wickremasinghe, A. C., & Walsh, E. M. (2015). Retrospective Cohort Study of Phototherapy and Childhood Cancer in Northern California, 137(6).
34. Ngoc Le, T., Reese, J. (2017). Bronze Baby Syndrome. The Journal of Pediatrics, 188, 301–301.e1. https://doi.org/10.1016/j.jpeds.2017.05.005
35. Kopelman AE, Brown RS, Odell GB. The “bronze” baby syndrome: a complication of phototherapy. J Pediatr 1972; 81:466-72.
36. Raub, A. G., Hwang, S., Horikoshi, N., Cunningham, A. D., Rahighi S., Wakatsuki S., Mochly-Rosen D. (2019). Small-Molecule Activators of Glucose-6-phosphate Dehydrogenase (G6PD) Bridging the Dimer Interface, 92618, 1321–1324. https://doi.org/10.1002/cmdc.201900341
37. Hwang, S., Mruk, K., Rahighi, S., Raub, A. G., Chen, C. H., Dorn, L. E., Horikoshi, N., Wakatsuki, S., Chen, J. K., & Mochly-Rosen, D. (2018). Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator. Nature communications, 9(1), 4045. https://doi.org/10.1038/s41467-018-06447-z
Published
2020-12-17
How to Cite
Ravikumar, N., & Greenfield, G. (2020). Glucose-6-phosphate Dehydrogenase Deficiency: A Review . International Journal of Medical Students, 8(3), 281–287. https://doi.org/10.5195/ijms.2020.637
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