Genomes and Genes
glucosephosphate dehydrogenase deficiency
Summary: A disease-producing enzyme deficiency subject to many variants, some of which cause a deficiency of GLUCOSE-6-PHOSPHATE DEHYDROGENASE activity in erythrocytes, leading to hemolytic anemia.
- Pamba A, Richardson N, Carter N, Duparc S, Premji Z, Tiono A, et al. Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone. Blood. 2012;120:4123-33 pubmed publisher..Therefore, contrary to current perception, in clinical terms the A- type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735. ..
- Carter N, Pamba A, Duparc S, Waitumbi J. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials. Malar J. 2011;10:241 pubmed publisher..G6PD status did not impact baseline haemoglobin, parasitaemia or temperature or the outcomes of anti-malarial therapy. Clinicaltrials.gov: NCT00344006 and NCT00371735. ..
- Amiwero C, Olatunji P. Re-evaluation of methaemoglobin reduction as a screening procedure for glucose-6-phosphate dehydrogenase (G6PD). Afr J Med Med Sci. 2007;36:177-81 pubmed..With sensitivity and specificity each of 93.3%, the simple qualitative test is dependable and therefore suitable for screening for G6PD. ..
- Louicharoen C, Nuchprayoon I. G6PD Viangchan (871G>A) is the most common G6PD-deficient variant in the Cambodian population. J Hum Genet. 2005;50:448-52 pubmed..We concluded that G6PD Viangchan (871G>A) was the most common mutation among Cambodians. This finding is similar to G6PD-deficient Thais and Laotians, suggesting a common ancestry of people from these three countries. ..
- Brewer G. Rediscovery of the susceptibility of G6PD deficient persons to methemoglobinemia from oxidant drugs, and to hemolysis from methylene blue. Am J Hematol. 2007;82:87-8 pubmed
- Luzzatto L. Glucose 6-phosphate dehydrogenase deficiency: from genotype to phenotype. Haematologica. 2006;91:1303-6 pubmed
- Peters A, Van Noorden C. Glucose-6-phosphate dehydrogenase deficiency and malaria: cytochemical detection of heterozygous G6PD deficiency in women. J Histochem Cytochem. 2009;57:1003-11 pubmed publisher..For women, the cytochemical assay is recommended. However, this assay is more expensive and difficult to perform and should be simplified into a kit for use in developing countries. ..
- Pinna A, Solinas G, Masia C, Zinellu A, Carru C, Carta A. Glucose-6-phosphate dehydrogenase (G6PD) deficiency in nonarteritic anterior ischemic optic neuropathy in a Sardinian population, Italy. Invest Ophthalmol Vis Sci. 2008;49:1328-32 pubmed publisher..20). The frequency of G6PD deficiency in patients with NAION was significantly lower than expected. Results suggest that G6PD-deficient patients in the Sardinian population have a significantly decreased risk of having NAION. ..
- Minucci A, Moradkhani K, Hwang M, Zuppi C, Giardina B, Capoluongo E. Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the "old" and update of the new mutations. Blood Cells Mol Dis. 2012;48:154-65 pubmed publisher..Finally, for the "old" mutations, we tried to verify features previously reported and, when subsequently modified, we updated the specific information using the latest literature data. ..
- Beutler E, Duparc S. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg. 2007;77:779-89 pubmed..Additionally, the issues important for conducting larger clinical trials in populations in which G6PD deficiency is prevalent are examined, with a particular focus on antimalarial drug development. ..
- Azma R, Hidayati N, Farisah N, Hamidah N, Ainoon O. G6PD enzyme activity in normal term Malaysian neonates and adults using a OSMMR2000-D kit with Hb normalization. Southeast Asian J Trop Med Public Health. 2010;41:982-8 pubmed..The quantitation of G6PD enzymes using this OSMMR-D kit with Hb normalization was simple since the Hb was analyzed simultaneously and the results were reproducible with a CV of less than 5%. ..
- Louicharoen C, Patin E, Paul R, Nuchprayoon I, Witoonpanich B, Peerapittayamongkol C, et al. Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast Asians. Science. 2009;326:1546-9 pubmed publisher..We found that the G6PD-Mahidol(487A) variant reduces vivax, but not falciparum, parasite density in humans, which indicates that Plasmodium vivax has been a driving force behind the strong selective advantage conferred by this mutation. ..
- Cocco P, Fadda D, Schwartz A. Subjects expressing the glucose-6-phosphate dehydrogenase deficient phenotype experience a lower cardiovascular mortality. QJM. 2008;101:161-3 pubmed
- Tagarelli A, Piro A, Bastone L, Condino F, Tagarelli G. Reliability of quantitative and qualitative tests to identify heterozygotes carrying severe or mild G6PD deficiency. Clin Biochem. 2006;39:183-6 pubmed..A cytochemical test is more sensitive than differential pH-metry to identify heterozygous G6PD- subjects. A cytochemical test is a reliable method for mass screening for G6PD deficiency to identify G6PD- heterozygotes. ..
- Sirdah M, Reading N, Perkins S, Shubair M, Aboud L, Prchal J. Hemolysis and Mediterranean G6PD mutation (c.563 C>T) and c.1311 C>T polymorphism among Palestinians at Gaza Strip. Blood Cells Mol Dis. 2012;48:203-8 pubmed publisher..1311T polymorphism. This work provides a foundation for the population screening of Palestinians for G6PD deficiency and for investigations of ancestral origin of the Mediterranean variant in world populations. ..
- Kaplan M, Hoyer J, Herschel M, Hammerman C, Stevenson D. Glucose-6-phosphate dehydrogenase activity in term and near-term, male African American neonates. Clin Chim Acta. 2005;355:113-7 pubmed..G-6-PD-deficient neonates formed a separate subgroup from those with normal enzyme activity. The data supplied should facilitate interpretation of G-6-PD test results. ..
- White N, Qiao L, Qi G, Luzzatto L. Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common. Malar J. 2012;11:418 pubmed publisher..25 mg base/kg) would be safer and equally effective. This lower dose could be deployed together with ACTs without G6PD testing wherever use of a specific gametocytocide is indicated. ..
- Ho H, Cheng M, Chiu D. Glucose-6-phosphate dehydrogenase--from oxidative stress to cellular functions and degenerative diseases. Redox Rep. 2007;12:109-18 pubmed..The present review covers recent developments in this field. Additionally, molecular characterization of G6PD variants, especially those frequently found in Taiwan and Southern China, is also addressed. ..
- Shekalaghe S, ter Braak R, Daou M, Kavishe R, van den Bijllaardt W, van den Bosch S, et al. In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrob Agents Chemother. 2010;54:1762-8 pubmed publisher..PQ may cause moderate anemia when coadministered with artemisinins, and excluding individuals based on G6PD status alone may not be sufficient to prevent PQ-induced hemolysis. ..
- Pinna A, Pes A, Zinellu A, Carta A, Solinas G. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and senile cataract in a Sardinian male population, Italy. Ophthalmic Epidemiol. 2009;16:395-9 pubmed publisher..G6PD deficiency does not represent a pathogenetic factor for early cataract formation, at least not in the Northern part of Sardinia. ..
- Shimizu H, Tamam M, Soemantri A, Ishida T. Glucose-6-phosphate dehydrogenase deficiency and Southeast Asian ovalocytosis in asymptomatic Plasmodium carriers in Sumba island, Indonesia. J Hum Genet. 2005;50:420-4 pubmed..No alterations in the prevalence of asymptomatic malaria infection suggest that parasite invasion into erythrocytes is unlikely to be a target phase in which the two polymorphisms demonstrate possible protective effects against malaria. ..
- Fanello C, Karema C, Avellino P, Bancone G, Uwimana A, Lee S, et al. High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency. PLoS ONE. 2008;3:e4031 pubmed publisher..Screening for G6PD deficiency before drug administration of potentially pro-oxidants drugs, like dapsone-containing combinations, although seldom available, is necessary. ..
- Jalloh S, Van Rostenberghe H, Yusoff N, Ghazali S, Nik Ismail N, Matsuo M, et al. Poor correlation between hemolysis and jaundice in glucose 6-phosphate dehydrogenase-deficient babies. Pediatr Int. 2005;47:258-61 pubmed..Hemolysis is not a main determinant of neonatal jaundice in G6PD-deficient babies. ..
- Chien Y, Lee N, Wu S, Liou J, Chen H, Hwu W. Changes in incidence and sex ratio of glucose-6-phosphate dehydrogenase deficiency by population drift in Taiwan. Southeast Asian J Trop Med Public Health. 2008;39:154-61 pubmed..G6PD deficiency screening has confirmed a subtle genetic flow in Taiwan. Besides the psychosocial effects, medical issues caused by population movements should be carefully watched in the future in Taiwan. ..
- Burgoine K, Bancone G, Nosten F. The reality of using primaquine. Malar J. 2010;9:376 pubmed publisher..vivax transmission, the risks associated with its use must be minimized during its deployment. In areas where P. vivax exists, patients should be tested for G6PD deficiency and adequately informed before administration of primaquine. ..
- Maisels M. Neonatal jaundice. Pediatr Rev. 2006;27:443-54 pubmed
- Algur N, Avraham I, Hammerman C, Kaplan M. Quantitative neonatal glucose-6-phosphate dehydrogenase screening: distribution, reference values, and classification by phenotype. J Pediatr. 2012;161:197-200 pubmed publisher..Female values were presented as a continuum preventing accurate classification but were classified based on male phenotype for practical use. ..
- Carette C, Dubois Laforgue D, Gautier J, Timsit J. Diabetes mellitus and glucose-6-phosphate dehydrogenase deficiency: from one crisis to another. Diabetes Metab. 2011;37:79-82 pubmed publisher..G6PD deficiency and diabetes can aggravate each other, and diabetes could be aetiologically associated with G6PD deficiency. ..
- Luzzatto L, Seneca E. G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications. Br J Haematol. 2014;164:469-80 pubmed publisher..Finally, we sketch the triangular relationship between malaria, antimalarials such as primaquine, and G6PD deficiency: which is to some extent protective against malaria, but also a genetically determined hazard when taking primaquine. ..
- Jiang W, Yu G, Liu P, Geng Q, Chen L, Lin Q, et al. Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in Chinese population. Hum Genet. 2006;119:463-78 pubmed
- Beutler E. Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. Blood. 2008;111:16-24 pubmed..In this brief historical review, we trace the discovery of this defect, its clinical manifestations, detection, population genetics, and molecular biology. ..
- Baird J, Surjadjaja C. Consideration of ethics in primaquine therapy against malaria transmission. Trends Parasitol. 2011;27:11-6 pubmed publisher..The early clinical work does not seem to afford an adequate assessment of safety in G6PDd patients. Potential risk of harm without clinical benefit to the patient raises ethical questions that should be examined. ..
- Ainoon O, Boo N, Yu Y, Cheong S, Hamidah H, Lim J. Complete molecular characterisation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a group of Malaysian Chinese neonates. Malays J Pathol. 2004;26:89-98 pubmed..In conclusion we have completely characterized the molecular defects of a group of Chinese G6PD deficiency in Malaysia. The mutation distribution reflects the original genetic pool and limited ethnic admixture with indigenous Malays. ..
- Ninokata A, Kimura R, Samakkarn U, Settheetham Ishida W, Ishida T. Coexistence of five G6PD variants indicates ethnic complexity of Phuket islanders, Southern Thailand. J Hum Genet. 2006;51:424-8 pubmed..The results suggest that several groups of people of the Asian Continent, such as Burmese, Laotian or Cambodian, Thai and Chinese, participated in the establishment of the ethnic identity of the current ethnic groups of Phuket Island. ..
- Arai M, Kosuge K, Kawamoto F, Matsuoka H. Reactivity of blood samples spotted onto filter papers in the WST-8 method for screening of G6PD deficiency. Acta Med Okayama. 2006;60:127-34 pubmed
- Suryantoro P. Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Yogyakarta and its surrounding areas. Southeast Asian J Trop Med Public Health. 2003;34 Suppl 3:138-9 pubmed..Molecular analysis among these 16 Javanese males showed the following mutations--nt563 (C->T) in 5 cases, nt1376 (G->T) in 3 cases, nt487 (G->A) in 2 cases, nt1311 (C->T) in 1 case with the remaining variants unknown. ..
- Rochford R, Ohrt C, Baresel P, Campo B, Sampath A, Magill A, et al. Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity. Proc Natl Acad Sci U S A. 2013;110:17486-91 pubmed publisher..This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations. ..
- Santana M, da Rocha M, Arcanjo A, Sardinha J, Alecrim W, Alecrim M. [Association of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in malaria patients treated with primaquine]. Rev Soc Bras Med Trop. 2007;40:533-6 pubmed..Investigation of the relationship between methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency showed that there was a possible association such that enzymopenic individuals may develop methemoglobinemia more frequently. ..
- Tantular I, Matsuoka H, Kasahara Y, Pusarawati S, Kanbe T, Tuda J, et al. Incidence and mutation analysis of glucose-6-phosphate dehydrogenase deficiency in eastern Indonesian populations. Acta Med Okayama. 2010;64:367-73 pubmed..Taken together, these findings may indicate that G6PD Vanua Lava is the most common variant in eastern Indonesian populations, except for Sikka. ..
- Ganesan S, Chaurasiya N, Sahu R, Walker L, Tekwani B. Understanding the mechanisms for metabolism-linked hemolytic toxicity of primaquine against glucose 6-phosphate dehydrogenase deficient human erythrocytes: evaluation of eryptotic pathway. Toxicology. 2012;294:54-60 pubmed publisher..The studies suggest that eryptosis mechanisms are not involved in accelerated removal of erythrocytes due to hemolytic toxicity of primaquine...
- Howes R, Piel F, Patil A, Nyangiri O, Gething P, Dewi M, et al. G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Med. 2012;9:e1001339 pubmed publisher..Please see later in the article for the Editors' Summary. ..
- Enevold A, Lusingu J, Mmbando B, Alifrangis M, Lemnge M, Bygbjerg I, et al. Reduced risk of uncomplicated malaria episodes in children with alpha+-thalassemia in northeastern Tanzania. Am J Trop Med Hyg. 2008;78:714-20 pubmed
- Youngster I, Arcavi L, Schechmaster R, Akayzen Y, Popliski H, Shimonov J, et al. Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug Saf. 2010;33:713-26 pubmed publisher..There is a need for evidence-based global consensus regarding medication use in G6PD-deficient patients. ..
- Kone A, Sagara I, Thera M, Dicko A, Guindo A, Diakite S, et al. Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali. Malar J. 2010;9:332 pubmed publisher..70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05). The presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT. ..
- Moiz B. Glucose-6-phosphate dehydrogenase (G6PD) screening in Pakistani neonates: to be or not to be. J Pak Med Assoc. 2007;57:618-20 pubmed
- Vafa M, Troye Blomberg M, Anchang J, Garcia A, Migot Nabias F. Multiplicity of Plasmodium falciparum infection in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants. Malar J. 2008;7:17 pubmed publisher..However some of these observations need to be confirmed including larger sample size with broader age range and using other msp2 genotyping method. ..
- Müller O, Mockenhaupt F, Marks B, Meissner P, Coulibaly B, Kuhnert R, et al. Haemolysis risk in methylene blue treatment of G6PD-sufficient and G6PD-deficient West-African children with uncomplicated falciparum malaria: a synopsis of four RCTs. Pharmacoepidemiol Drug Saf. 2013;22:376-85 pubmed publisher..This effect appears to be of limited clinical relevance but needs to be monitored. ..
- Graves P, Gelband H, Garner P. Primaquine for reducing Plasmodium falciparum transmission. Cochrane Database Syst Rev. 2012;:CD008152 pubmed publisher..Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment. ..