Frequency Of Glucose-6-phosphate Dehydrogenase Deficiency Research Articles

Study of the antigenic characteristics of red blood cells units and their sickle cell disease recipients and the G6PD activity of transfused red blood cells units

IntroductionLa transfusion occupe une place centrale au cours de la drépanocytose. La compatibilité des groupes sanguins des concentrés de globules rouges (CGR) avec ceux du patient est essentielle pour prévenir l'allo-immunisation. La concordance des CGR de donneurs d’origine africaine est la meilleure avec les patients drépanocytaires. Cependant, ces CGR peuvent présenter des caractéristiques altérant leur conservation et leur qualité, tel le déficit en glucose-6-phosphate déshydrogénase (G6PD). L'objectif est d'analyser les protocoles transfusionnels, les taux d'immunisation et les situations d’incompatibilité phénotypique au cours de la drépanocytose et d'évaluer la fréquence du déficit en G6PD dans les CGR de donneurs d'ancestralité africaine. MéthodeDes échantillons de CGR transfusés à des patients drépanocytaires ont été analysés. Les données transfusionnelles ont été collectées à partir des bases institutionnelles. L'activité de la G6PD a été mesurée dans un segment de CGR. RésultatsUn total de 98 échantillons de CGR transfusés à 37 patients au cours de 41 épisodes transfusionnels a été analysé. Parmi les patients, 35,1% (n=13) n’étaient pas alloimmunisés, 10,8% (n=4) avaient des anticorps contre Fya/Fyb, Jka/Jkb, M/N, S/s ; 21,6% (n=8) contre les antigènes RH/K. Dans tous les cas, le protocole transfusionnel était conforme aux recommandations. Un déficit en G6PD a été retrouvé pour 9 CGR, provenant tous de donneurs d’ancestralité afro-antillaise. ConclusionLes protocoles transfusionnels sont respectés et diminuent les réactions immunitaires. Les CGR de donneurs d'origine africaine, avec la meilleure phénocompatibilité, présentent un taux élevé de déficit en G6PD. La question de l’impact de ce déficit, quant à leur conservation et leur rendement transfusionnel doit se poser.

A positive correlation between mutated gene of sickle cell anemia and glucose-6-phosphate dehydrogenase among gond tribes of Chhattisgarh, India

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy affecting millions of individuals worldwide. It is believed that the prevalence of G6PD deficiency in different ethnic populations increases its association with other pathological conditions especially sickle cell anemia (SCA), as they both are well-known adaptations against malaria. Thus, the present study aims to determine the frequency of G6PD deficiency among SCA patients and the association between them in the tribal community (Gond) of Chhattisgarh, India. MethodA total of 810 samples from three different age groups i.e., 10–20, 21–30, and 31–40 years were collected from the tribal community (Gond) of Kabirdham district of Chhattisgarh. The frequency of SCA was determined by a slide test followed by cellulose acetate paper electrophoresis and G6PD deficiency by methemoglobin reduction test. Glutathione-S-Transferase (GST) gene polymorphism in sickle celled individuals and variant analysis in G6PD deficient individuals were analyzed by RT-PCR. ResultsThe frequency of SCA and G6PD deficiency was reported at 9.75% and 17.16% respectively and a high degree of positive correlation between SCA and G6PD deficiency was also found (HbSS-G6PD deficient: r = 0.84, p = .356; HbAS-G6PD deficient: r = 0.89, p = .345). Results of the GST gene revealed that GSTM1 and GSTT1 genes are present in almost all sickled individuals while GSTP1 and GSTP1a exist in the mutated form in a maximum percentage of individuals. G6PD variant analysis also showed that 70% and 60% of individuals have mutated Mahidol and Union variants respectively, while none of the individuals have mutated Chinese variants. ConclusionA high degree of correlation between SCA and G6PD was reported among Gond tribes of Chhattisgarh, India with a high degree of mutated GSTP1, GSTP1a, Mahidol, and Union variants. The study makes it possible to take specific preventive measures concerning the medication of anti-oxidizing drugs.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency in Neonates Presenting with Indirect Hyperbilirubinemia

Objective: To determine the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in neonates presenting with indirect hyperbilirubinemia.Methods: A prospective cross-sectional study was conducted at Neonatal intensive care unit (NICU) of National Institute of Child Health, Karachi from August 2020 to July 2021. All neonates with either gender born with indirect hyperbilirubinemia >5mg/dl admitted in NICU were consecutively enrolled. G6PD deficiency along with baseline and laboratory characteristics were observed. The presence of G6PD level of <1.3 U/g Hb was labeled as G6PD deficiency.Results: Of 228 neonates, the mean age was 8.58 ±3.68 days. There were 153 (67.1%) males and 75 (32.9%) females. The frequency of G6PD deficiency was found to be 72 (31.6%). The mean weight was significantly higher among neonates with G6PD deficiency as compared to the patients with no G6PD deficiency, i.e., 2.53 ±0.48 vs. 2.37 ±0.56 (p-value 0.035). A significant difference of hemoglobin level (p-value <0.001), serum total bilirubin level (p-value <0.001), and serum indirect bilirubin level (p-value0.001) was observed in between G6PD deficient and non-deficient neonates. Increased reticulocyte count was also found significantly higher in neonates with G6PD deficiency as compared to the neonates without G6PD deficiency, i.e., 69 (95.8%) and 34 (21.8%) respectively (p-value <0.001). Conclusion: G6PD deficiency was considerably prevalent in neonates with indirect hyperbilirubinemia. Moreover, hemoglobin level, serum total bilirubin level, serum indirect bilirubin level, and increased reticulocyte count was also observed significant contributing factors for G6PD deficiency.

Survey for glucose-6- phosphate dehydrogenase enzyme deficiency among premarital attendanceinniava

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is considered the most frequent enzyme deficiency world wide, several reports have focused on its prevalence in different regions of Iraq. The current study was initiated to report on the frequency of G6PD deficiency among male attendance to premarital center in Ninava governorate in Northern Iraq. A total of 806 male individuals attending the Public Health Laboratory for routine premarital investigations were screened for G6PD deficiency using methemoglobin reduction test (MRT). The results were confirmed by quantitative enzyme assay for the cases that showed G6PD deficiency. A total (759) out of (806) were MRT negative , and (47) out of (806) were MRT positive with a prevalence of (5.8%).

Low Density Plasmodium Infections and G6PD Deficiency Among Malaria Suspected Febrile Individuals in Ethiopia.

The identification and management of low parasitemia infections have become increasingly challenging for malaria control and elimination. Submicroscopic Plasmodium infections and G6PD deficiency among febrile patients require more sensitive diagnostic methods to improve detection and careful treatment regime of these infections. In Ethiopia, information on the low density submicroscopic malarial infections and frequency of G6PD deficiency (G6PDd) is scarce. In this study, 297 malaria suspected febrile patient samples were collected from health facilities of Bonga town in southwestern Ethiopia. The positivity rates of Plasmodium infection were determined by microscopy and quantitative PCR. G6PD activity level was determined by careSTART™ G6PD biosensor and the frequency of three common variants: G6PD*A (A376G), G6PD*A- (G202A) and Mediterranean (C563T) were investigated. G6PD gene sequencing was performed to detect mutations in exons 2-11 for both G6PD normal and deficient samples based on the phenotypic assay. More than twice Plasmodium infected samples was detected by qPCR (52/297; 17.4%) than microscopy (21/297; 7.0%). About 31 (10%) of the infections were submicroscopic. Bednet usage and age had a significant association with Plasmodium infection. Of the 271 participants who were tested for G6PD phenotype, 19 (7.0%) had low G6PD level. No mutations were observed in A376G, G202A, and C563T in the G6PDd samples, but three novel non-synonymous mutations in exon 2 including a C to T transition at position ChrX:6504 (Arg to Thr), G to T at ChrX:6369 (Ser to IIe), and G to C at ChrX:6664 (Gln to His) were detected. A high number of submicroscopic Plasmodium infections observed in this study pose a challenge for accurate and timely diagnosis, which could hinder malaria control efforts. G6PD deficiency in malaria patients pose danger when treating patients with primaquine. The three novel mutations detected in exon 2 of the G6PD gene merit further investigation on the hemolytic risk when exposed to oxidative antimalarials, their prevalence, and clinical significance.

Molecular Heterogeneity of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency in the Portuguese Population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme defect in the world, affecting more than 500 million people. In Portugal, the average frequency of G6PD deficiency in males was estimated at about 0.5% and since the year 2000 several G6PD-deficient alleles have been identified. The main goal of this study was to improve the knowledge on the molecular heterogeneity of G6PD deficiency in the Portuguese population. A retrospective analysis of the mutational profile of 138 unrelated Portuguese individuals (101 males; 37 females), with no known sub-Saharan ancestry, who had been diagnosed with G6PD deficiency between 1994 and 2020 at the Molecular Hematology Unit of Centro Hospitalar e Universitário de Coimbra. The molecular study was done by direct Sanger sequencing or PCR-RFLP analysis. Twenty-one different pathogenic mutations were found. Among them, 20 were missense, causing the amino acid change, and one was an in-frame deletion in exon 10. The three most frequent mutations belong to the G6PD c.376A>G African background haplotype, namely the G6PD variants: A- (c.202G>A; p.68Val>Met) (58.6%), Betica (c.968T>C; p.323Leu>Pro) (12.1%) and Santamaria (c.542A>T; p.181Asp>Val) (4.3%). There is a wide molecular heterogeneity of G6PD deficiency in the Portuguese population.

Glucose-6-Phosphate dehydrogenase deficiency associated hemolysis in a cohort of new onset type 1 diabetes children in Guangdong province, China

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, with a high prevalence in Guangdong, China. The purpose of this study was to explore the characteristics of newly diagnosed type 1 diabetes (T1D) patients with G6PD deficiency in a cohort of Chinese children and to investigate the relationship between the diabetic ketoacidosis (DKA) and hemolysis due to G6PD deficiency in these patients.MethodsA total of 503 newly diagnosed T1D children aged 6 months–18 years were collected and their G6PD enzyme activity were measured. Fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and G6PD gene were analysed. The pH, HCO3, and plasma osmotic pressure between DKA patients with and without hemolysis at the presentation were compared.ResultsIn the present study, G6PD deficiency accounted for 5.3% of newly diagnosed T1D children. There were no significant differences in FPG/HbA1c and HbA1c levels between T1D children alone and T1D children with G6PD deficiency. Hemolysis appeared in five of the twenty-two DKA patients with G6PD deficiency. Two patients had fever at onset and were given ibuprofen and cefazolin. The other three patients did not have infection or ingestion of hemolytic drugs. There were no significant difference in pH, HCO3, and osmotic pressure between the children with DKA with and without hemolysis at the presentation. The hemolysis occurred between 2 and 7 days after admission and the hyperglycaemia had been corrected by the time hemolysis occurs. Four G6PD gene mutations were found in the diabetes with G6PD deficiency patients: c.1376G > T, c.1388G > A, c.95A > G, and c.871G > A, all of which were genes with high frequency of G6PD deficiency in Guangdong Province. No correlation between genotype and hemolysis was found.ConclusionIn the present study, we found the frequency of G6PD deficiency among newly diagnosed T1D children was similar to that of the general population. However, DKA children with G6PD deficiency are prone to occur hemolytic anemia, and these hemolysis usually occurs when DKA is corrected and blood glucose is in homeostatic state, which is easy to be ignored. To reduce the risk of this complication, especially in areas with high incidence of G6PD deficiency, screening for G6PD activity in people with newly diagnosed diabetes should be considered.

Neonatal Screening for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency in Eastern India

Introduction: The overall magnitude of the frequency of G6PD deficiency ranges between 0 to 10 percent in the Indian population. This prospective study was planned to estimate the prevalence of G6PD deficiency in newborn population born in a tertiary care centre in Eastern India. Methods: This prospective observational study was undertaken among all consecutively delivered neonates born in a tertiary care teaching hospital of Eastern India, between Apr 2016 and Oct 2017. Prematurity less than 32 weeks and perinatal asphyxia requiring extensive resuscitation were excluded from the study. Umbilical cord blood samples were collected in a EDTA containers, drawn from the placental side of the umbilical cord incised while severing it at the time of birth. The G6PD levels were estimated quantitatively based on ultraviolet (UV) method by quantitative sphectrophotometric assay using ILab 650 fully automated analyzer. All babies wherein the cord blood G6PD levels was less than 6.95 mU/g of Hb was taken as deficient. Results: Mean (SD) of G6PD at birth was 12.56 (3.45) mU/g of Hb. Out of 1037 neonates, five were found to be G6PD deficient. There was increased incidence of neonatal jaundice requiring phototherapy in G6 PD deficient neonates, and it was statistically significant. Conclusion: The prevalence of G6PD deficiency was 0.48% in term and late preterm neonates as assessed quantitatively in cord blood

A Study on the Relevance of Glucose-6-Phosphate Dehydrogenase Level Screening in Patients with Rheumatic Diseases Prior to Initiating Treatment With Hydroxychloroquine.

ObjectiveDrug-induced hemolytic anemia can occur in patients with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. The practice of G6PD-deficiency screening in the rheumatology field has been inconsistent. This study aimed to determine the utility of screening prior to the initiation of hydroxychloroquine and/or sulfasalazine in rheumatology patients in the ambulatory clinics at Stony Brook University Hospital, New York.MethodsWe conducted a retrospective chart review of cases of rheumatic diseases that were screened for G6PD deficiency at Stony Brook University Hospital ambulatory clinics. Demographic details and relevant clinical and laboratory data of the patients were collected. The data from similar studies in the literature were searched for and reviewed.ResultsThis study consisted of 228 patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren’s syndrome. Among those patients, 94.7% received hydroxychloroquine, sulfasalazine, or dapsone; 41% (89/228) of patients were screened for G6PD deficiency, and the majority of them were on treatment with hydroxychloroquine. Of those patients, 7.9% (five Caucasians and two African Americans) were found to have G6PD deficiency, and two of the G6PD-deficient patients received hydroxychloroquine. There was no incidence of hemolytic anemia documented in any of the seven patients with G6PD deficiency. We reviewed the literature and found three similar studies of patients receiving hydroxychloroquine with no reported hemolytic anemia from different medical centers in the US, and the frequency of G6PD deficiency reported in these studies was 1.4%, 4.0%, and 4.2%, respectively.ConclusionsOur study suggests that the frequency of G6PD deficiency in our rheumatic population is similar to that of the general population, and the risk of hemolytic anemia in G6PD deficiency associated with hydroxychloroquine is extremely rare. Hence, G6PD screening may not be recommended prior to starting treatment with hydroxychloroquine.

Frequency of G6PD Deficiency in General Population at District Bannu, Khyber Pakhtunkhwa, Pakistan

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disease and it is a common enzymaticdisease of RBCs in humans X linked recessive condition are more common in males than females. The said deficiency leads toaffecting >400 million people worldwide Individuals, normally males, with deficient alleles are helpless to neonatal jaundice andintense hemolytic anemia, usually during disease, after treatment with specific medications or subsequent to eating Fava beans..Objective: To measure the frequency of Glucose-6-Phosphate-Dehydrogenase deficiency in general population at district Bannu,Khyber Pakhtunkhwa Pakistan.Material and Methods: This cross-sectional descriptive study was conducted on 500 human subjects, who were referred forG6PD assay, in Samad clinical Laboratory, District Bannu Khyber Pakhtunkhwa, Pakistan, from July 2018 to July 2019. 500ccvenous whole blood was collected in EDTA containing vial, for G6PD Test. (Span Diagnostic S.A.R.L, France). Patients of any Age,Sex & area having fever, hematuria, headache, visible jaundice, family history, malaria and anemia were included in this study,while patients suffering from renal disease, any malignancy & not willing persons were excluded.Results: Out of the total 500 hundred, 370 (74%) were males and females were 130 (26%). Total 64/500 (12.8 %) were G6PDdeficient, with 55 male and 09 were female. Malaria positive with G6PD deficiency were 13/64 (20.31%), with 12 males and onefemale. Statistically significant difference among each group (p= 0.0022) was noted. Mean age of the G6PD deficient persons was(2.8 ± 1.03) years. Anemia was graded as Hemoglobin less than 11.5g/dl was taken as anemia. Severe anemia as Hb < 7 g/dl,moderate anemia as Hb ranged between 7-10 g/dl and mild if Hb ranged between 10-11.5 g/dl.Among 370 males, 86 persons had hemoglobin of less than 11.5 g/dl, 42 had hemoglobin 7-10 g/dl and 7 patients had hemoglobinless than 7 g/dl, only 235 patients had hemoglobin more than 11.5, among 130 females, 33 patients had hemoglobin of less than11.5 g/dl, 17 patients had hemoglobin 7-10 g/dl and 05 patients had hemoglobin less than 7 g/dl, only 75 patients had hemoglobinmore than 11.5 g/dl.Conclusion: This study shows high frequency of G6PD Deficiency in district Bannu Khyber Pakhtunkhwa Pakistan especially veryhigh frequency in males than females.

Hemoglobin S and Glucose-6-Phosphate Dehydrogenase Deficiency Coinheritance in AS and SS Individuals in Malaria-Endemic Region: A Study in Calabar, Nigeria.

Background:Malaria placed a huge burden on human life and has been reported to be a key health problem affecting developing countries. This study was designed to assay for glucose-6-phosphate dehydrogenase (G6PD) status and malaria parasite density of individuals with sickle cell gene in University of Calabar Teaching Hospital, Calabar.Subjects and Methods:The methemoglobin method was used to determine the G6PD status. Thick blood films were used to ascertain the malaria parasite density while hemoglobin genotype was determined using cellulose acetate paper electrophoresis with tris ethylenediaminetetracetic acid borate buffer (pH 8.6). Thirty hemoglobin SS (HbSS) and 30 hemoglobin AS (HbAS) individuals were recruited for the study while 30 hemoglobin AA (HbAA) individuals were recruited as control.Results:The study showed a high frequency of G6PD deficiency (17.78%) in the study area while G6PD deficiency was significantly (P < 0.05) higher in HbAA individuals (33.33%) when compared to HbSS (10.00%) and HbAS (10.00%) individuals. The prevalence of malaria parasitemia and parasite density was comparable in the three hemoglobin variants. The distribution of malaria parasitemia and parasite density in both gender among the various hemoglobin variants showed no association (P > 0.05). G6PD deficiency distribution in both gender were found to be comparable (P > 0.05). The distribution of malaria parasitemia in the various hemoglobin variants in the G6PD-deficient individuals showed no significant difference (P > 0.5). However, the parasite density of the HbAS (3100 ± 1828.48 μL) and HbSS (2400 ± 1687.06 μL) were significantly lower than that of HbAA (4040 ± 1529.44 μL).Conclusion:The result of this study supports the hypothesis that inheriting the G6PD deficiency gene and sickle cell gene (both in homozygous and heterozygous form) reduces the severity of malaria parasite infection and hence protects against severe acute malaria while having less effect on infection.

Prevalence of G6PD deficiency and associated haematological parameters in children from Botswana

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is commonly seen in malaria endemic areas as it is known to confer a selective advantage against malaria. Recently, we reported a high proportion of asymptomatic reservoir of Plasmodium vivax in Botswana, that calls for intervention with primaquine to achieve radical cure of vivax malaria. Considering that individuals with this enzyme deficiency are at risk of haemolysis following primaquine treatment, assessment of the population for the relative frequency of G6PD deficiency is imperative. Samples from 3019 children from all the districts of Botswana were successfully genotyped for polymorphisms at positions 202 and 376 of the G6PD gene. Haematological parameters were also measured. The overall population allele frequency (based on the hemizygous male frequency) was 2.30% (95% CI, 1.77–2.83), while the overall frequency of G6PD-deficient genotypes A- (hemizygote and homozygote genotypes only) was 1.26% (95% CI, 0.86–1.66). G6PD deficiency is spread in Botswana according to the historical prevalence of malaria with a North-West to South-East decreasing gradient trend. There was no association between G6PD status and P. vivax infection. G6PD A- form was found to be associated with decreased RBC count and haemoglobin levels without a known cause or illness. In conclusion, we report for the first time the prevalence of G6PD deficiency in Botswana which is relevant for strategies in the malaria elimination campaign. Further work to examine the activities of the enzyme in the Botswana population at risk for malaria is warranted.

The Laboratorial Diagnosis for G6PD Deficiency in Multiethnic Population

The deficiency of glucose-6-phosphate dehydrogenase (G6PD) is the most frequent of the causes of hemolytic anemias by enzymopathies. Considering the high prevalence of these alterations and the miscegenated characteristic of the Brazilian population, the objective of this study was to investigate the frequency of this genetic affection, correlating them with the ethnic aspects and with the importance of the methodologies used for the routine laboratory diagnosis. A total of 544 peripheral blood samples collected after informed consent were analyzed from individuals aged 16-65, including 426 blood donors and 118 from individuals in an educational institution. The samples were submitted to the classic laboratory diagnosis methods for G6PD deficiency, with subsequent confirmation by complementary and specific methodologies. For the G6PD deficiency, a frequency of 3.86% was found, with 81.48% of the samples presenting the mutation A-202 (G> A), of African origin. The high frequency of G6PD deficiency reinforces the importance of investigating these hereditary conditions with due laboratory confirmation especially in mixed populations.

Frequency of G6PD Mediterranean in individuals with and without malaria in Southern Pakistan

BackgroundPakistan has an estimated annual burden of 1.5 million malaria cases. The current situation calls for an effective malaria control and eradication programme in this country. Currently, primaquine is an attractive option for eliminating reservoirs of Plasmodium vivax hypnozoites and killing gametocytes of Plasmodium falciparum. However, this drug causes haemolysis in individuals who are glucose-6-phosphate (G6PD) deficient. It is important to map G6PD deficiency and malaria distribution in Pakistan to design an effective malaria eradication regimen. Frequency of G6PD deficiency (G6PDd) in malaria patients has not been reported from Pakistan in any meaningful way. The purpose of this study was to evaluate the frequency of G6PD c.563C>T (G6PD Mediterranean) in male individuals with and without falciparum malaria.MethodsTwo hundred and ten archived DNA samples from males (110 from falciparum malaria patients and 100 from healthy individuals) were utilized in this study. Healthy blood donors were selected based on stringent pre-defined criteria. Patients were confirmed for malaria parasites on microscopy and or immune chromatographic assay detecting P. falciparum histidine-rich protein 2. Parasitaemia was also computed. DNA samples were tested for G6PD c.563C>T mutation through PCR–RFLP according to the previously defined protocol and its allelic frequency was computed.ResultsG6PD c.563C>T was observed in four of 110 patients with falciparum malaria and in two of 100 healthy donors. Mean (± SD) haemoglobin, median (IQR) platelet and median (IQR) parasite count in G6PD-deficient malaria-patients were 8.9 ± 0.9 g/dL, 124 × 109/L (IQR 32, 171) and 57,920/μL of blood (IQR 12,920, 540,000) respectively.ConclusionsCumulative allelic frequency for G6PD 563c.C>T was 0.0285 detected in 6 of 210 X-chromosomes in Southern Pakistan. Frequency for this G6PD allele was 0.0364 in malaria-patients and 0.0200 in healthy individuals. Large studies including females are needed to elucidate the true burden of G6PDd in malaria-endemic areas. The information will enable local health policy makers to design effective strategies for eliminating malaria form this region.

Effect of age, period and birth–cohort on the frequency of glucose-6-phosphate dehydrogenase deficiency in Sardinian adults

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited disorder common in Sardinia. In this study, the frequency variation of G6PD-deficiency across age groups and birth cohorts was investigated using Age–Period–Cohort analysis.Methods: Data were collected from the clinical records of 11,252 patients (6975 women, age range 17–94 years) who underwent endoscopy between 2000 and 2016 at a teaching hospital (University of Sassari), Italy. G6PD status was assessed by enzymatic assay based on G6PD/6GPD ratio. A Poisson log-linear regression model was used to identify age and time trend in G6PD deficiency.Results: Enzyme deficiency was detected in 11.4% of the entire cohort (men: 7.9%; women: 13.6%). Age–Period–Cohort analysis showed no inflection points across age groups, especially after age 80. The effects of time period and birth cohorts on G6PD deficiency were negligible (frequencies before and after 1950 were 11.0% and 11.8%, respectively).Conclusions: These findings indicate that the frequency of G6PD deficiency does not vary significantly in oldest subjects. The lack of evidence for selection across the malaria eradication time may be explained by other factors, including somatic cell selection or misclassification of heterozygotes women as G6PD normal in the older birth cohorts. Additional molecular studies may help clarify these issues.Key messageThe frequency of glucose-6-phosphate dehydrogenase deficiency is stable across age groups and does not vary in generations born before or after malaria eradication.

G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon

BackgroundPlasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria. In Brazil, few studies have reported the frequency of G6PD deficiency (G6PDd) present in malaria-endemic areas. This is particularly important, as G6PDd screening is not currently performed before primaquine treatment. The aim of this study was to determine the prevalence of G6PDd in the region of Alto do Juruá, in the Western Brazilian Amazon, an area characterized by a high prevalence of P. vivax infection.MethodsFive-hundred and sixteen male volunteers were screened for G6PDd using the fluorescence spot test (Beutler test) and CareStart™ G6PD Biosensor system. Demographic and clinical-epidemiological data were acquired through an individual interview. To assess the genetic basis of G6PDd, 24 SNPs were genotyped using the Kompetitive Allele Specific PCR assay.ResultsTwenty-three (4.5%) individuals were G6PDd. No association was found between G6PDd and the number of malaria cases. An increased risk of reported haemolysis symptoms and blood transfusions was evident among the G6PDd individuals. Twenty-two individuals had the G6PDd A(−) variant and one the G6PD A(+) variant. The Mediterranean variant was not present. Apart from one polymorphism, almost all SNPs were monomorphic or with low frequencies (0–0.04%). No differences were detected among ethnic groups.ConclusionsThe data indicates that ~1/23 males from the Alto do Juruá could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. G6PD A(−) is the most frequent deficiency allele in this population. These results concur with reported G6PDd in other regions in Brazil. Routine G6PDd screening to personalize primaquine administration should be considered, particularly as complete treatment of patients with vivax malaria using chloroquine and primaquine, is crucial for malaria elimination.

G6PD DEFICIENCY

Context: Hyperbilirubinemia due to glucose 6 phosphate dehydrogenase(G6PD) deficiency can cause permanent neurological damage and death in neonates.Screening for the enzyme enables timely diagnosis and treatment in cases of G6PD relatedkernicterus. Knowledge of patient G6PD status is also important in treatment of malaria, adisease endemic in Pakistan. World Health Organization recommends mandatoryuse ofprimaquine for radical cure and eradication of malaria. Since, Primaquine, causes hemolysisin G6PD deficient cases, widespread adoption of the drug is viewed with caution. Aims: Thisstudy assessed frequency of G6PD deficiency in Pakistani noenates and examines the need forits screening based on local disease prevalence and malaria endemicity. Settings and Design:A cross sectional study was carried at Hematology Department, Army Medical College (NUST),in collaboration with Military Hospital, Rawalpindi, Pakistan.(January - August, 2011). Methodsand Material: The frequency of G6PD deficiency in newborn population was determined byquantitative (spectrophotometric) method. Cord blood (2.5 ml blood in K3EDTA bottle) sampleswere obtained from 240 newborns (male: female 1.2:1) after informed consent from parents.Statistical analysis used: Data obtained was analyzed using SPSS Windows version 17.Results: Frequency of G6PD deficient cases was 4.2%. Among the ten G6PD deficient patients,six had severe enzyme deficiency (&lt;10% enzyme activity). Conclusions: The local prevalenceof G6PD deficiency and its potential complications qualify it as a disease that must be screenedfor. Also, prior knowledge of patient G6PD status enables the physician to revert to modifiedtreatment regimen for malaria only in enzyme deficient cases and not otherwise.

G6PD deficiency and absence of α-thalassemia increase the risk for cerebral vasculopathy in children with sickle cell anemia.

The aim of this study was to test the association between hematological/genetic factors and cerebral vasculopathy in children with sickle cell anemia (SCA). A group with cerebral vasculopathy (VASC) was composed of children who had stroke (n = 6), silent infarct (n = 11), or an abnormal transcranial Doppler (n = 5). Eighty-four patients had neither positive history of stroke or silent infarct, nor abnormal transcranial Doppler (NORM group). An intermediate group (COND; n = 15) was composed of SCA children with a conditional transcranial Doppler. Biological analyses were performed on samples obtained at steady state and before the beginning of any chronic treatment. The comparisons of the three groups demonstrated a protective effect of α-thalassemia against cerebral vasculopathy through its effects on hemoglobin and reticulocyte levels. Moreover, we observed higher frequency of G6PD deficiency in the VASC group compared with the other groups. Our study confirms the key role of α-thalassemia and G6PD status in the pathophysiology of cerebral vasculopathy in SCA children.

Newborn screening for G6PD deficiency: A 2-year data from North India

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythrocyte enzymopathy, being present in more than 400 million people worldwide that may lead to neonatal jaundice or hemolytic crisis due to drugs or infections. In our study, we aimed to study the frequency of G6PD deficiency in neonates and the proportion of deficient neonates, who developed neonatal hyperbilirubinemia in the study population. The study was an observational one, conducted at the Division of Genetics of Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, over a 2-year period from January 2011 to December 2012. A total of 6,000 newborns delivered during that period underwent newborn screening on 24-72 h of birth. Neonatal hyperbilirubinemia was presented in 13.3% of the study population. Of female neonates, 16% demonstrated G6PD deficiency. This is worth noting for an X-linked recessive trait. Thus, in view of a high gene frequency for a disorder that is manageable with just elimination of few drugs and foodstuff, we stress the need for a newborn screening program for G6PD deficiency.

Characterization of G6PD genotypes and phenotypes on the northwestern Thailand-Myanmar border.

Mutations in the glucose-6-phosphate dehydrogenase (G6PD) gene result in red blood cells with increased susceptibility to oxidative damage. Significant haemolysis can be caused by primaquine and other 8-aminoquinoline antimalarials used for the radical treatment of Plasmodium vivax malaria. The distribution and phenotypes of mutations causing G6PD deficiency in the male population of migrants and refugees in a malaria endemic region on the Thailand-Myanmar border were characterized. Blood samples for G6PD fluorescent spot test (FST), G6PD genotyping, and malaria testing were taken from 504 unrelated males of Karen and Burman ethnicities presenting to the outpatient clinics. The overall frequency of G6PD deficiency by the FST was 13.7%. Among the deficient subjects, almost 90% had the Mahidol variant (487G>A) genotype. The remaining subjects had Chinese-4 (392G>T), Viangchan (871G>A), Açores (595A>G), Seattle (844G>C) and Mediterranean (563C>T) variants. Quantification of G6PD activity was performed using a modification of the standard spectrophotometric assay on a subset of 24 samples with Mahidol, Viangchan, Seattle and Chinese-4 mutations; all samples showed a residual enzymatic activity below 10% of normal and were diagnosed correctly by the FST. Further studies are needed to characterise the haemolytic risk of using 8-aminoquinolines in patients with these genotypes.