Article

Prevalence of Erythrocyte Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency in the Population of Western Turkey

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Abstract

Newborn G6PD deficiency screening has been recognized as an essential component of public health care in most developed and some Mediterranean countries. However, such screening is yet to be widely embraced in Turkey. The aim of the present study was to determine the normal values of G6PD and deficiency prevalence of this enzyme in different age groups of people living in the western region of Turkey and accordingly inform and educate about favism to those asymptomatic carriers who usually are not aware of their G6PD deficient status. A total of 1421 clinically healthy individuals without evidence of leukocytosis or thrombocytosis were included in the study. Activity of G6PD was quantitatively measured. Normal mean values of G6PD in healthy males were 8.94 +/- 8.65 IU/g Hb (or 231.73 +/- 43.16 IU/10(12) RBC), in females were 9.16 +/- 3.78 IU/g Hb (or 219.9 +/- 43.1 IU/10(12) RBC). The frequencies of severe and mild G6PD deficiencies were 0.44% and 6.07% in females, respectively, whereas in males it was 7.24%. Overall frequency of the G6PD-deficient phenotype was detected as 6.9%. There is no significant statistical difference of G6PD activity between males and females, although frequency of the G6PD-deficient phenotype is relatively high in western Turkey. The results emphasize a need for screening for G6PD deficiency before prescribing anti-malarial therapy with drugs like primaquine to patients in this region of Turkey known for its prevalence of malaria.

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... Low activities of G6PD render red blood cells susceptible to hemolysis under certain conditions such as ingestion of fava beans, certain drugs, and severe infections [1], [4]. G6PD deficiency is one of the most common human enzyme deficiencies, affecting more than 400 million people worldwide [5], [6]. Common clinical manifestations of G6PD-deficient subjects are neonatal jaundice and acute hemolytic anemia [7]. ...
... G6PD deficiency is the most significant factor that contributes to severe neonatal hyperbilirubinaemia and kernicterus [9], [10] . Distribution of the deficiency varies among different populations reflecting geographic and ethnic variations [6] with high prevalence in the Middle East [4]. Antioxidant vitamins (E and C) are considered one of the defense systems against reactive oxygen species [11]. ...
Article
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The mechanism by which glucose-6-phosphate dehydrogenase (G6PD) deficiency causes neonatal hyperbilirubinemia is not completely understood. However, the genetic disorder G6PD deficiency predisposes red blood cells to oxidative stress. The aim of this study was to establish the relationship between plasma antioxidant vitamin (E and C) levels and the development of hyperbilirubinemia in full-term neonates with deficient G6PD. A total of 196 live birth neonates of healthy mothers were included in this study. Twelve of them were deficient in G6PD. In addition to demographic data, serum total bilirubin, hemoglobin, hematocrit, and vitamin E and C levels were measured on the first day after birth. Neonates with G6PD deficiency (n=7) who did not develop hyperbilirubinemia (mean serum bilirubin level of 70.8+/-23 micromol/l, median 71.8) and neonates with G6PD deficiency (n=4) who developed hyperbilirubinemia (mean serum bilirubin level of 226.7+/-79 micromol/l, median 233.4) on the first day of life had similar gestational weights and age. The second group, however, had lower hemoglobin and hematocrit as well as plasma vitamin C and E levels. None of these results showed significant difference. The results of the present study indicate that red blood cell hemolysis as a result of inadequate antioxidants system in G6PD-deficient neonates is not the only contributing factor for hyperbilirubinemia.
... Interestingly, Turkey is a pioneer country that has set its standard of G6PD enzyme levels. 4 The values of the G6PD enzyme in different age groups of people in Turkey have been determined. The normal mean values of G6PD in healthy females were 9.16 ± 3.78 IU/g Hb and 8.94 ± 8.65 IU/g Hb in males. ...
... The normal mean values of G6PD in healthy females were 9.16 ± 3.78 IU/g Hb and 8.94 ± 8.65 IU/g Hb in males. 4 In the study methodology, Kılıç et al 1 stated that the disease was diagnosed by the suspected clinical picture and low G6PD enzyme levels. The laboratory normal range for the G6PD enzyme level employed in the study was 7-20.5 IU/g of Hb. ...
... The cause of prolonged jaundice can be explained by bilirubin generated by persistent hemolysis. The prevalence of G6PD enzyme deficiency was reported as 6-13% in studies conducted in Turkey [19][20][21]. It was 1.1% (n: 1) in our study. ...
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Objectives: Prolonged jaundice is a common condition among neonates. İt is defined as persisting hyperbilirubinemia after the 14th day following birth for term babies and after the 21st day for premature babies with serum bilirubin level higher than 5mg/dL. Prolonged unconjugated hyperbilirubinemia may be associated with some pathological conditions. We aimed to evaluate the etiological, clinical and laboratory findings of babies with prolonged jaundice. Methods: This descriptive cross-sectional study included 90 infants with prolonged jaundice in the pediatric outpatient clinic of Ordu University Training and Research Hospital between 1 January 2015 and 1 October 2020. Demographic characteristics, physical examination and laboratory findings of the babies were collected and analyzed to determine the etiology of neonatal hyperbilirubinemia. Results: In total 90 infants with prolonged jaundice were presented in this study, including 50 male and 40 female neonates. The most common causes of prolonged neonatal jaundice were breastfeeding, Rh or ABO incompatibility, and urinary tract infection 73%, 13% and 8% of neonates, respectively. Conclusion: Breast milk jaundice is the most common cause of prolonged jaundice in infants. Although there are some explanations for breast milk jaundice, the exact mechanism leading to breast milk jaundice is not clear. Other reasons that may affect the infants later in life should be investigated in a short time.
... Deficiency can cause hemolysis episodes triggered by infections, drug use or ingestion of fava beans (1). Herein, we aimed to present a case of G6PD deficiency due to the fava ingestion in a geriatric patient.Frequency of G6PD deficiency in Turkey varies between %1 to %5-20 in southwestern Anatolia(2). Most people with G6PD deficiency are not aware of their defect, they are asymptomatic until their first attack. ...
... Females that code for the abnormal gene for G-6-PD on both of their x-chromosomes are homozygous female while heterozygote female had two red cell populations, normal cells and a deficient cell, since one of their x-chromosome carries the defective G-6-PD gene. Therefore, severe enzyme deficiency occurred in hemizygous males and homozygous females while heterozygous females have normal or moderately lower enzyme level [26,27]. This extremely high rate for female deficient volunteers may be due to different Screening procedures which are quite robust in the detection of the fully developed defect in hemizygous males and female homozygous, but they fall short in the ascertainment of female heterozygote. ...
Article
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Background: Transfusion from glucose-6-phosphate dehydrogenase (G-6-PD) deficient and Sickle cell traits (HbAS) blood constitute a major health burden and social challenge, especially to jaundiced neonate and sickle cell disease patient. Currently, routine screening of these two abnormal genes on blood donors in our locality is yet to be introduced. However, this study aimed at bridging the gap. Methodology: This study screened 1000 volunteers for G-6-PD deficiency using methaemoglobin reduction method. Haemoglobin phenotypes of the deficient subjects were determined by alkaline cellulose acetate electrophoresis. Results: Out of 1000 volunteers; 36.7% were G-6-PD deficient [128 (36.2%) were males; 248 (62.5%) were females]. Haemoglobin phenotypes (HbAA, HbAS, HbSS, HbAC, HbSC and HbCC) of these deficient subjects were; 71.30%, 23.90%, 0.50%, 3.70%, 0.30% and 0.30% respectively. Original Research Article Jelani et al.; AJMAH, 2(3): 1-6, 2017; Article no.AJMAH.30243 2 No incidence of HbSS, HbSC, and HbCC in G-6-PD deficient male was recorded. Conclusion: Co-inheritance with G-6-PD deficiency and HbAS is high. This finding has importance in blood transfusion setting, as routine screening of these inherited disorders prior to blood donation may help in reducing the potential risk of haemolytic complications and also prevent failure of white blood cell filtration among high risk persons.
... Prevelance of G6PD deficiency in Turkey is 0.5%; however, prevelance in Cukurova region is 8.2% [6]. A study on prevelance of G6PD in West Turkey showed 0.44% severe and 6.07% mild enzyme deficiency in women and 7.24% deficiency in men [7]. Although most of the patients are asypmtomatic, some patients have hemolytic anemia episodes whereas other patients have chronic hemolysis. ...
... The patients who are 15 years old and above are treated with 30 mg primaquine/day for 14 days and chloroquine given 600 mg followed by 300 mg 6 h later and 300 mg once a day at second and third days (MoH, 2010). Studies exhibiting the deficiency of G6PD in Turkey were between the ranges of 1.2-10% altering for different ethnic groups (Akoglu et al., 1981;Keskin et al., 2002;Turan, 2006). Nowadays in Turkey, blood samples of malaria patients were not checked routinely for G6PD -deficiency; only the suspected malaria patients were screened for G6PD -deficiency and all patients with G6PD -deficiency were treated under supervision of medical doctors or in hospitals/clinics. ...
Article
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Turkey is located in the middle of Asia, Africa and Europe, close to Caucasia, Balkans and Middle East in subtropical climate zone. Malaria has been known since the early ages of human history and it was one of the leading diseases in Anatolian history, as well. Today, chloroquine-sensitive Plasmodium vivax is the only agent of autochthonous malaria cases in Turkey. The other Plasmodium species identified are isolated from imported cases of malaria. The most common vector of malaria in Turkey is Anopheles sacharovi followed by An. superpictus, An. maculipennis and An. subalpinus. In 2009, pre-elimination stage of Malaria Program was started due to dramatic decline in the number of malaria cases in Turkey (Total, 84; 38 autochthonous cases only in 26 foci in south-eastern Anatolia, and 46 imported cases; incidence: 0.1/100,000). As there were no detected cases of new autochthonous malaria in the first 8 months of 2010, elimination stage was started. The role of the persistent policies and successful applications of the Ministry of Health, such as the strict control of the patients using anti-malarial drugs especially chloroquine, avoidance of resistant insecticides, facilitation of access to patients via Health Transformation Program (HTP), establishment of close contact with the patients' families, and improvement of reporting and surveillance system, was essential. In addition, improvement maintained in the motivations and professional rights of malaria workers, as well in the coordination of field studies and maintenance of a decline or termination in vector-to-person transmission were all achieved with the insistent policies of the Ministry of Health. Other factors that probably contributed to elimination studies include lessening of military operations in south-eastern Anatolia and the lowering of malaria cases in neighbouring countries in recent years. Free access to health services concerning malaria is still successfully conducted throughout the country.
... NFS 282 2.1 Khneisser (2006) [231] NFS 3000 1.2 Oman White (1986) [232] EAA 172 38.4 Al-Riyami (2003) [233] EAA 6342 17.9 3252 17.6 3090 10.2 Saudi Arabia Gelpi (1965) [234] BCB 820 7.1 306 15.0 514 2.3 Gelpi (1967) [235] DIP 648 27.3 419 30.5 229 21.4 Gelpi (1977) [236] NFS 369 18.2 Warsy (1985) [237] EAA 607 19.9 El-Hazmi (1986) [238] EAA 3120 9.4 1817 12.6 1303 4.8 Samuel (1986) [239] MRT 1112 7.3 766 7.6 346 6.6 El-Hazmi (1989) [240] EAA 847 12.3 519 12.7 328 11.6 El-Hazmi (1991) [241] EAA 429 4.9 232 6.9 197 2.5 Saleem (1991) [242] EAA 3291 1.9 El-Hazmi (1994) [243] EAA 689 31.3 352 30.4 307 35.5 El-Hazmi (1995) [244] EAA 820 6.7 469 7.7 351 5.4 Al-Nuaim (1997) [245] EAA 1039 1.9 527 3.6 512 0.2 El-Hazmi (1999) [246] EAA 9130 16.4 5130 17.6 4000 14.6 Muzaffer (2005) [247] NFS 2505 2.0 1278 3.1 1227 0.9 Syria Usanga (2000) [215] NFS 737 3.0 Turkey Say (1965) [248] NFS 2231 1.3 1944 1.4 287 0.3 Aksu (1990) [249] NFS 1521 6.8 728 7.4 793 6.3 Keskin (2002) [250] NFS 1950 1.2 1032 1.5 918 1.0 Atay (2006) [251] EAA 624 3.8 330 5.5 294 2.4 Turan (2006) [252] EAA 1421 6.9 746 7.2 675 6.5 United Arab Emirates White (1986) [232] ...
Article
Glucose-6-phosphate deficiency is the most prevalent enzyme deficiency, with an estimated 400 million people affected worldwide. This inherited deficiency causes neonatal hyperbilirubinemia and chronic hemolytic anemia. Although most affected individuals are asymptomatic, exposure to oxidative stressors such as certain drugs or infection, can elicit acute hemolysis. To characterize the global prevalence of G6PD deficiency, we conducted a systematic review of the G6PD deficiency literature, drawing studies from various databases, including MEDLINE/Pubmed and Biosis. Selected studies included cross-sectional and longitudinal studies published between 1960 and 2008. Additionally, meta-analytic procedures were employed to assess the degree of heterogeneity amongst prevalence estimates and, where appropriate, pool them. The searches yielded a total of 280 prevalence estimates, corresponding to 88 countries. The highest prevalence rates were reported among Sub-Saharan African countries, even after adjusting for assessment method. Meta-analysis revealed a high degree of heterogeneity for regional and global prevalence estimates. This heterogeneity in reported estimates appeared to be due to differences in G6PD deficiency assessment and diagnostic procedures. The magnitude and variation in global, regional, and country-level prevalence rates of G6PD deficiency are of public health import, particularly in planning programs to improve neonatal health and in the distribution of various medications, especially antimalarial drugs, as G6PD deficiency is most prevalent in malaria-endemic areas.
Thesis
Northern Pakistan, Khyber Pakhtunkhwa (KP) is low malaria endemic area characterised by seasonal transmission with predominantly vivax malaria. Migration of high number of Afghan Refugees in 1978 into KP led to concerns for an increase in malaria, as the malaria incidence in this group was reportedly high compared to the local Pakistani population. Considerable progress has been made in controlling malaria through operational research in the camps where the Afghan refugees reside. However, this process requires effective, repeatable active surveillance tools for monitoring malaria control as availability of accurate data is the major challenge at present. The aim of this PhD project was to generate current information on malaria infection rates through parasite prevalence and malaria exposure using antimalarial antibody responses.The project also investigated the risk factors of malaria and heterogeneity in the geographic distribution of malaria in the camps by using GIS data with serological responses and parasite prevalence data. As an ancillary objective the project aimed to determine the prevalence of G6PO deficiency in the study population. A cross-sectional survey was conducted in five Afghan refugee camps of KP between June and September in 2010. Blood samples were obtained on filter paper from 2526 individuals and tested by rapid diagnostic test, paraSite species specific PCR and ElISA for antibody responses to Plasmodium vivax and Plasmodium falciparum. A questionnaire was administered to collect household and individual based information to determine the potential risk factors of malaria. Heterogeneity in malaria was observed between the studied camps based on seroprevalence, which ranged from 17%-45% for P. vivax and 3% to 11% for P. falciparum. Variation in P. vivax infection prevalence was also detected between the camps, which ranged from 0.4-9% (ROT) and 5-15% (peR). Variation in the distribution of malaria was also found within the camp using spatial/GIS data with clear foci of infection identified in 4 of 5 camps. The results showed that as expected parasite based prevalence measures (ROT and peR) are significantly lower than serological measure of exposure. P. falciparum infection prevalence (ROT and PCR) and seroprevalence was found to be extremely low with P. vivax infections predominant. Age seroprevalence changes were more pronounced for P. vivax than P. falciparum and seroconversion rate was strongly associated with parasite rate. Increasing age .and poorly built houses were associated with increasing risk, while staying in the same camp for the last 6 months and using measures to reducing vector biting such as repellents repellent, coils or insecticide spraying were associated with reduce risk of falciparum malaria. The risk of vivax malaria was observed to increase with increasing age, sharing house with cattle and having fever within 24 hours or two weeks and a reduction in the risk was seen in the individuals who reported use of Insecticide treated Bed Nets (ITN) night prior to surveyor used self protection measures from vector. The 563C-T polymorphism of G6PD gene was observed in only 2 unrelated individuals out of 505 individuals tested (O.4%). In conclusion, both parasitological and serological measures were able to detect spatial variation in infection and exposure to malaria at the micro epidemiological level within the camp. This data will help to provide beneficial and up-to-date information to manage control activities in the study area.
Article
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythrocyte enzyme deficiency in the world. The epidemiological, biochemical and molecular studies on G6PD enzyme deficiency performed over the past 50 years are summarized herein, with special emphasis on the findings of studies related to the enzyme deficiency in Turkey.
Data
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Dataset S1. Bibliography of sources from which surveys included in the model were identified. doi:10.1371/journal.pmed.1001339.s001 Protocol S1. Assembling a global database of G6PD deficiency (G6PDd) prevalence surveys. (S1.1) Overview of database requirements. (S1.2) Library assembly. (S1.3) Dataset inclusion criteria. (S1.4) Survey diagnostic methods. (S1.5) The final G6PDd survey dataset. (S1.6) Defining MECs' limits. doi:10.1371/journal.pmed.1001339.s002 Protocol S2. Model based geostatistical framework for predicting G6PDd prevalence maps. (S2.1) Model requirements in relation to G6PD genetics. (S2.2) The model. (S2.3) Model implementation. (S2.4) Overview of mapping procedure. (S2.5) Uncertainty. doi:10.1371/journal.pmed.1001339.s003 Protocol S3. Model validation procedures and results. (S3.1) Creation of the validation datasets. (S3.2) Model validation methodology. (S3.3) Validation results. doi:10.1371/journal.pmed.1001339.s004 Protocol S4. Demographic database and population estimate procedures. (S4.1) GRUMP-beta human population surface. (S4.2) Areal prediction procedures. doi:10.1371/journal.pmed.1001339.s005 Protocol S5. Mapping the prevalence of G6PDd in females. (S5.1) Overview of G6PDd in females. (S5.2) Heterozygous G6PDd expression and diagnosis. (S5.3) Overview of female data in the G6PD database. (S5.4) Modelling phenotypic G6PDd prevalence in females. (S5.5) Maps of G6PDd in females and population estimates. (S5.6) Improving the map of G6PDd in females. doi:10.1371/journal.pmed.1001339.s006 Protocol S6. Developing an index of overall national-level risk from G6PD deficiency. (S6.1) G6PDd variants database. (S6.2) Generating an index of national-level risk from G6PDd. (S6.3) Generating an uncertainty index of the national-level risk index categories. doi:10.1371/journal.pmed.1001339.s007 Table S1. National-level demographic metrics and G6PDd allele frequency and population estimates. doi:10.1371/journal.pmed.1001339.s008 Table S2. National areal prediction summary statistics and Monte Carlo standard error (SE) for each model output. doi:10.1371/journal.pmed.1001339.s009 Table S3. Reported observations of class II and III G6PD variants from malaria endemic countries. doi:10.1371/journal.pmed.1001339.s010
Article
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Background: GLucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common known enzymopathy in human. G6PD deficiency is usually asymptomatic, however, deficient individuals are at increased risk of developing acute hemolytic anemia and hyperbilirubinemia following intake of oxidative agents and fava. The objective of present study was to detect prevalence of G6PD deficiency in admitted males for premarriage tests in Zahedan Reference Laboratory. Also, we compared blood indices of normal and G6PD deficient individuals.Materials and Methods: This descriptive study was carried out on 1340 admitted males in Zahedan Reference Laboratory from February 2008 to March 2009. G6PD activity was determined in EDTA containing blood samples by qualitative fluorescence spot test, then G6PD deficiency was confirmed by quantitative spectrophotometric method. Total leukocyte count and RBC indices of G6PD deficient samples and the same number of normal samples were compared. The differences between two groups were compared using Sigmaplot software and t-Student test. A P-value less than 0.05 was considered statistically significant.Results: G6PD deficiency was found in 84 individuals of total 1340 by fluorescence spot test and confirmed in 79 by quantitative method. Therefore, prevalence of G6PD deficiency in Zahedan was estimated to be 5.9%. Comparison of deficient and normal individuals did not show significant difference in WBC count, RBC count, hemoglobin concentration, hematocrit, mean corpuscular hemoglobin (MCH) and RDW-SD. However, mean corpuscular volume (MCV) was significantly high and mean corpuscular hemoglobin concentration (MCHC) and RDW-CV were significantly low in G6PD deficient individuals compared to those with normal enzyme level.Discussion: Present study revealed that the prevalence of G6PD deficiency in Zahedan is 5.9%. Severity of G6PD deficiency in quantitative assay indicated that class I and II are probably dominant variants in Zahedan
Article
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis. However, this disease affects both males and females. In Turkey, the frequency of this enzyme deficiency was reported to vary, from 0.25 to 18%, by the geographical area. Its prevalence in the northern Black Sea region of Turkey is unknown. The aims of this study were to assess the prevalence of G6PD deficiency in the northern region Turkey in children and adults with hyperbilirubinemia and hemolytic anemia. This report included a total of 976 G6PD enzyme results that were analyzed between May 2005 and January 2014. G6PD deficiency was detected in 5.0% of all patients. G6PD deficiency was significantly less frequent in females (1.9%, 6/323) than in males (6.6%, 43/653). G6PD deficiency was detected in 3.7% of infants with hyperbilirubinemia, 9.2% of children, and 4.5% of adults with hemolytic anemia. In both the newborn group and the group of children, G6PD deficiency was significantly more frequent in males. In the combined group of children (groups I and II), the proportion of males was 74% and 67% in all groups (P = .0008). In conclusion, in northern region of Turkey, G6PD deficiency is an important cause of neonatal hyperbilirubinemia and hemolytic crisis in children and adults. This study suggests that most pediatricians thought that G6PD deficiency is exclusively a male disease. For this reason, some female patients may have been undiagnosed.
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Background: Primaquine is a key drug for malaria elimination. In addition to being the only drug active against the dormant relapsing forms of Plasmodium vivax, primaquine is the sole effective treatment of infectious P. falciparum gametocytes, and may interrupt transmission and help contain the spread of artemisinin resistance. However, primaquine can trigger haemolysis in patients with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd). Poor information is available about the distribution of individuals at risk of primaquine-induced haemolysis. We present a continuous evidence-based prevalence map of G6PDd and estimates of affected populations, together with a national index of relative haemolytic risk. Methods and findings: Representative community surveys of phenotypic G6PDd prevalence were identified for 1,734 spatially unique sites. These surveys formed the evidence-base for a Bayesian geostatistical model adapted to the gene's X-linked inheritance, which predicted a G6PDd allele frequency map across malaria endemic countries (MECs) and generated population-weighted estimates of affected populations. Highest median prevalence (peaking at 32.5%) was predicted across sub-Saharan Africa and the Arabian Peninsula. Although G6PDd prevalence was generally lower across central and southeast Asia, rarely exceeding 20%, the majority of G6PDd individuals (67.5% median estimate) were from Asian countries. We estimated a G6PDd allele frequency of 8.0% (interquartile range: 7.4-8.8) across MECs, and 5.3% (4.4-6.7) within malaria-eliminating countries. The reliability of the map is contingent on the underlying data informing the model; population heterogeneity can only be represented by the available surveys, and important weaknesses exist in the map across data-sparse regions. Uncertainty metrics are used to quantify some aspects of these limitations in the map. Finally, we assembled a database of G6PDd variant occurrences to inform a national-level index of relative G6PDd haemolytic risk. Asian countries, where variants were most severe, had the highest relative risks from G6PDd. Conclusions: G6PDd is widespread and spatially heterogeneous across most MECs where primaquine would be valuable for malaria control and elimination. The maps and population estimates presented here reflect potential risk of primaquine-associated harm. In the absence of non-toxic alternatives to primaquine, these results represent additional evidence to help inform safe use of this valuable, yet dangerous, component of the malaria-elimination toolkit. Please see later in the article for the Editors' Summary.
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is relatively common in populations exposed to malaria. This deficiency appears to provide some protection from this infection, but it can also cause hemolysis after administration of some antimalarial drugs, especially primaquine. The risk of drug-induced G6PD deficiency-related hemolysis depends on a number of factors including the G6PD variant, the drug and drug dosage schedule, patient status, and disease factors. Although a great deal is known about the molecular biology of G6PD, determining the potential for drug-induced hemolysis in the clinical setting is still challenging. This report discusses the potential strategies for assessing drug-induced G6PD deficiency-related hemolytic risk preclinically and in early clinical trials. 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.
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Background. The objective of this study was to determine the prevalence of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency among the population of the Croatian Adriatic Coast, part of the Mediterranean basin. Methods. The fluorescent spot test was used to screen 2,726 randomly selected high school students in the Croatian Adriatic coastal area. Fluorescence readings were performed at the beginning and at 3, 6, 10, and 25 min of incubation. Results were classified into the following three groups: bright fluorescence (BF), weak fluorescence (WF), and no fluorescence (NF). All NF and WF samples at 3 min were quantitatively measured using the spectrophotometric method. Results. Twelve persons, 10 boys and 2 girls, were found to be deficient in G-6-PD, rendering a 0.44% prevalence of G-6-PD deficiency. All NF samples at fluorescent spot test were G-6-PD-deficient. WF at 3 min of the incubation period was present in 33 (1.2%) subjects, and only 2 (6%) were true positive. Fluorescence reading at 10 min of incubation omits five (41%) of the G-6-PD deficient samples. Conclusions. Prevalence of G-6-PD deficiency in the Croatian Adriatic coastal population is 0.44%. Fluorescent spot test for moderate enzyme deficiency is reliable in early fluorescence reading. (C) 2001 IMSS. Published by Elsevier Science Inc.
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The Jews of Kurdistan are a small inbred population with a high incidence of beta-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Recently, it was reported that the beta-thalassaemia in this population shows an unusual mutational diversity; 13 different mutations were identified, of which 4 had not previously been observed in any other population. In contrast, we now report that the G6PD deficiency, which has the highest known incidence in the world, and which affects about 70% of males, is almost entirely attributable to a single widespread mutation, G6PD Mediterranean.
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Glucose-6-phosphate dehydrogenase deficiency, one of the most common human enzymatic defects, is characterized by extreme molecular and biochemical heterogeneity. The molecular bases of almost all polymorphic italian variants have now been identified and the overall heterogeneity is lower than expected from biochemical data. We examined 161 G6PD-deficient subjects (130 males and 31 females) originating from different parts of Italy. G6PD activity and molecular characterization were determined in all the subjects analyzed. We found the G6PD Mediterranean genotype in roughly 70%, G6PD Union and G6PD Seattle in about 6% and G6PD A- in 4% of the samples analyzed. G6PD S. Antioco and G6PD Cosenza were less frequent (1.2%), and single cases of G6PD Partenope and G6PD Tokyo were also detected. We report the frequency and distribution of the most common G6PD variants in Italy. Greater molecular heterogeneity than described by others was observed, especially in Sardinia. Among the severe deficient variants, G6PD Mediterranean has a higher prevalence in Sardinia (83%) than in continental Italy (61%), as does G6PD Union (10% and 4%, respectively). G6PD Seattle and A-, associated with mild G6PD deficiency, are by contrast more frequent in continental Italy.
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Sporadic cases of drug-induced haemolytic anaemia due to glucose-6-phosphate dehydrogenase (G6PD) deficiency in patients belonging to Vataliya Prajapati community prompted us to study the prevalence of G6PD deficiency in the community. Screening for G6PD deficiency was carried out using the dichlorophenol-indophenol (DPIP) dye decolorization method. A total of 471 individuals were screened. Of these, 385 unrelated individuals were considered to calculate the prevalence of G6PD deficiency. Among 272 unrelated males, 76 persons (27.94%) and among 113 unrelated females, 11 individuals (9.73%) were found to be G6PD deficient. A quantitative assay on 41 of the G6PD deficient samples showed the enzyme activity ranged from 0-0.5 unit/ml RBC/min. The prevalence of G6PD deficiency in Vataliya Prajapatis community was found to be the highest ever reported in the Indian caste-groups population studied so far.
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Unlabelled: Glucose 6-phosphate dehydrogenase (G-6-PD) deficiency is common in the Thai population and is the cause of neonatal hyperbilirubinemia and hemolytic anemia. This X-linked disorder is much more common in males than females. The objectives of this study were to compare the result of the screening methemoglobin reduction test (MRT) with the gold standard G-6-PD activity, and also to determine the prevalence of G-6-PD deficiency in the cord blood and blood of neonates with hyperbilirubinemia. Five hunderd and twenty two randomly selected cord blood (350 males, 172 females) and 229 peripheral blood from neonates with hyperbilirubinemia were assayed for G-6-PD enzyme activity using a WHO-recommended standard test as well as methemoglobin reduction (MR) test. The results showed that prevalence of G-6-PD deficiency from the cord blood was 11.1 per cent in males, and 5.59 per cent in females. Among newborns with neonatal jaundice, the prevalence of G-6-PD deficiency was 22.1 per cent in males and 10.1 per cent in females. MRT in cord blood G-6-PD deficiency screening had acceptable sensitivity (85.7%) and high specificity (98.1%). The sensitivity of MRT in jaundiced infants was low (60.0%) whereas the specificity was acceptable (92.1%). The negative predictive values were more than 90 per cent while the positive predictive values were low (61-65%) from both specimens. Conclusions: G-6-PD deficiency is common in the Thai population, both in males and females and can be screened from cord blood by using low cost MRT. G-6-PD deficiency contributes to 20 per cent of neonatal jaundice, and screening with MRT yields low sensitivity.
Article
Objective: Glucose 6-phosphate dehydrogenase (G6PD) deficiency manifests genetic polymorphism and prevalence of its varying among geographic regions and ethnic groups. G6PD deficiency is important in Gaziantep, Turkey because high deficiency prevalence was observed in Adana and Antakya, the neighbouring Mediterranean cities. Methods: In this study, sera from 306 subjects (166 female, 140 male) between 1-80 years old were for erythrocyte G6PD activity with International Committee for Standardization in Hematology (ICSH) method. After excluding the outliers, 95% interpercentile interval was accepted as reference limit. Results: In Gaziantep reference group erythrocyte G6PD activity limits for subjects over one year old are 6.4 - 13.2 U/g Hb, 30°C. Seven subjects with low enzyme activities indicate that G6PD deficiency frequency is approximately 2.3 ± 1% in Gaziantep. Conclusion: G6PD deficiency frequence is approximately 2.3 ± 1 % in Gaziantep which is higher than the mean prevalence in Turkey.
Article
67/369 male Saudi subjects (18%) were found to be G6PD deficient on screening, and electrophoresis of blood samples stored on filter paper strips revealed B-like variants with intermediate enzyme activity in 11%, presumed Mediterranean variant in 13%, Gd+ (A+) in 2%, Gd–(A–7) in 0.8%, and indeterminate enzyme status in 6% of the subjects tested. A significant association between G6PD deficiency and hemoglobin S correlated with previous studies on similar samples from the same general population.
Article
We evaluated the Greek screening program for glucose-6-phosphate dehydrogenase (G6PD) deficiency, which was incorporated into the existing national phenyketonuria (PKU) screening program to identify infants with G6PD deficiency and eliminate the induction of acute hemolytic crisis by informing the families about the extrinsic factors that G6PD-deficient patients should avoid. Between 1977 and 1989, 1,286,000 infants were screened. The fluorescent spot test was used on samples extracted from dried blood spots. Abnormal fluorescence due to G6PD deficiency (severe or partial) was found in 3.14% of the samples (1 in 22 males and 1 in 54 females). The sensitivity of the test for homozygosity and hemizygosity was 100%. In heterozygosity the test identifies only subjects who have considerably diminished enzyme activity. The test is inexpensive when added to the PKU screening program ($0.90 US per test). We believe that screening a population for G6PD deficiency is justified if the incidence of the deficiency in the population is high and the clinical manifestations serious. The fluorescent spot test is recommended because it is reliable, easy to perform, and inexpensive. The test must be performed within a fortnight from sampling, and the cards must not be exposed to high temperature or humidity.
Article
Glucose-6-phosphate dehydrogenase (1.1.1.49) activity was assessed in 1986-1988 in blood samples from 1,521 individuals from 375 families living an Antalya city and adjacent villages by Beutler's fluorescence spot test. The families were randomly selected by the State Statistical Institute. Complete deficiency occurred in 7.4% of males and 1.8% of females. Mean enzyme activity was 6.77 +/- 1.07 IU/g Hb in normals and ranged between 0 and 0.48 IU/g Hb in those considered deficient. Kinetic measurements made with partially purified enzyme showed that GdB+ and GdB- variants were present in normal and in deficient subjects, respectively.
Article
We have evaluated the hypothesis of a negative association between glucose 6-phosphate dehydrogenase (G6PD) deficiency and cancer in a cohort of 481 Sardinian males with hematological malignancies. The frequency of G6PD deficiency in the patients was not different from the incidence in a group of 16,219 controls. The same conclusion resulted from the comparison of the frequency of expression of the GdB gene in 23 heterozygous women having a clonal hematologic disease and a control group of 37 healthy heterozygotes. Therefore at present there is no evidence that G6PD deficiency has a protective effect against development of hematologic neoplasms.
Article
In this paper, the author has not attempted to review all aspects of the G6PD system but rather to illustrate, by way of some specific aspects, that the heavy investment of nearly two decades of work in this area has yielded significant returns. Some questions remain unanswered, and several new developments are only just opening up. In the area of red cell biochemistry and physiology, the information that can be derived from the comparative study of G6PD variants is discussed. The regulation of NADPH generation in the erythrocyte can now be analyzed rather precisely but in spite of this the exact sequence of events culminating in drug induced hemolysis remains unclear and presently poses what seems to be the most challenging physiopathological problem in this area. The patterns, and to some extent the mechanism of in vivo enzyme inactivation, have been characterized; and the mode of regulation of enzyme turnover in nucleated cells, such as the erythrocyte precursors, has been discussed. This latter process might now be approached experimentally in cultured fibroblasts, which appear to be also the ideal material for a further exploration of the possibilities of genetic complementation and recombination, as outlined in the section on cellular genetics. In view of the direct data now available on the selective role of malaria, the study of population dynamics of Gd alleles has passed the stage of geographic description only. In order to explain the mechanism of selection, in the near future studies at the cellular level may hopefully be undertaken using in vitro cultures of P. falciparum in human red cells from subjects with various hemoglobin and G6PD genotypes.
Article
135 Turks living in the vicinity of Antalya, a Turkish city on the Mediterranean coast, were studied for haemoglobin variants, beta-thalassaemia G-6-PD deficiency and haptoglobin types. The incidence of Hb-S was 2.3%. 8 beta-thalassaemic individuals with increased Hb-A2 and patient with 1 sickle cell-beta2-thalassaemia disease were found. The incidence of beta-thalassaemia with increased Hb-A2 was 6.7% and that of G-6-PD deficiency was 5.4%. The distribution of haptoglobin types in these people was very similar to that found in Turkish people in general; the only exception was the presence of Hp O in 2 individuals without haemolytic disorder. Gene frequencies of Hp1 and Hp2 were 0.26 and 0.7p4, respectively.
Article
We describe a case of favism in a female newborn infant with glucose-6-phosphate dehydrogenase (G6PD) deficiency whose mother had ingested fava beans 5 days before delivery. At birth there were clinical and hematologic signs of hemolytic anemia, hemoglobinuria, and no blood group immunization. Study of the G6PD activity and 2-deoxy-glucose-6-phosphate utilization rate revealed that the infant and the mother were heterozygous for G6PD deficiency.
Article
Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene is inhibited by addition of polyunsaturated fat to a high-carbohydrate diet and stimulated by feeding a high-carbohydrate diet to starved mice. The mechanism of this regulation is posttranscriptional. To define the regulated step, we measured the abundance of G6PD mRNA both in the nucleus and in total RNA. Feeding mice a high-fat diet results in a 70% or greater inhibition of nuclear precursor mRNA (pre-mRNA) and mature mRNA abundance. Amounts of both pre-mRNA and mature mRNA for G6PD are stimulated 13-fold or more by refeeding starved mice. Changes in amount of pre-mRNA for G6PD are of a similar magnitude and precede the changes in amount of mature mRNA for G6PD in total RNA. These changes in pre-mRNA abundance occur in the absence of observable changes in the rate of transport of mRNA from the nucleus to the cytoplasm, splicing of the pre-mRNA, or degradation at the 3'-end of the transcript. Despite large changes in pre-mRNA amount in mice fed a low-fat diet relative to mice fed a high-fat diet, the rate of change in the amount of pre-mRNA during the diurnal feeding cycle is not altered. Thus, expression of G6PD is regulated at an early step after transcription of the pre-mRNA. We suggest that pre-mRNA which enters the processing pathway is stable and can be processed and transported to the cytoplasm where it is translated.
Article
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythrocytic enzymatic disorder in Italy and is characterized by wide clinical, biochemical and molecular variability. We studied the clinical and hematologic data from 54 G6PD-deficient, unrelated males from the Apulia region. Analyses for enzymatic activity, G6PD electrophoresis and molecular typing were performed on all subjects. Thirty-nine subjects (72.2%) showed a severe G6PD deficiency (<10% residual enzymatic activity) and 15 subjects (27.8%) a moderate deficiency (10--60% residual activity). The Mediterranean variant was found in 48.2% of cases, the Seattle variant in 33.3%, the A- variant in 7.45% and the Montalbano variant in 3.7%; the variant was not identified in four subjects. Thirty-two patients (59.2%) were asymptomatic; of these, 37.04% demonstrated acute hemolytic crises induced mainly by ingestion of fava beans and 3.7% had had neonatal jaundice. Acute hemolytic anemia was found in 53.8% of subjects with the Mediterranean variant, in 5.5% with the Seattle variant, in 100% with the A-variant and 0% with the Montalbano variant. Enzymatic activity was shown to be a poor predictive parameter of acute hemolytic crises and was not correlated with clinical features. Subjects with Mediterranean or A- variants had a more severe clinical phenotype which was not related to enzymatic activity. The Seattle, and probably the Montalbano, variant appears to have a milder clinical expression.
Article
The objective of this study was to determine the prevalence of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency among the population of the Croatian Adriatic Coast, part of the Mediterranean basin. The fluorescent spot test was used to screen 2,726 randomly selected high school students in the Croatian Adriatic coastal area. Fluorescence readings were performed at the beginning and at 3, 6, 10, and 25 min of incubation. Results were classified into the following three groups: bright fluorescence (BF), weak fluorescence (WF), and no fluorescence (NF). All NF and WF samples at 3 min were quantitatively measured using the spectrophotometric method. Twelve persons, 10 boys and 2 girls, were found to be deficient in G-6-PD, rendering a 0.44% prevalence of G-6-PD deficiency. All NF samples at fluorescent spot test were G-6-PD-deficient. WF at 3 min of the incubation period was present in 33 (1.2%) subjects, and only 2 (6%) were true positive. Fluorescence reading at 10 min of incubation omits five (41%) of the G-6-PD deficient samples. Prevalence of G-6-PD deficiency in the Croatian Adriatic coastal population is 0.44%. Fluorescent spot test for moderate enzyme deficiency is reliable in early fluorescence reading.
The Metabolic and Molecular Bases of Inherited Diseases
  • L Luzzatto
  • A Mehta
Luzzatto L, Mehta A. Glucose-6-phosphate dehydrogenase deficiency. In: Scriver CR, ed. The Metabolic and Molecular Bases of Inherited Diseases. 7th ed. NewYork: Harper Row;1995. pp. 3367-3398.
Greek newborn infants
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Glucose-6-phosphate dehydrogenase
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  • Hd Waller
Lohr GW, Waller HD. Glucose-6-phosphate dehydrogenase. In: Bergmeyer HU, ed. Methods of Enzymatic Analyses. New York: Academic Press;1974. p. 636.