Glucose-6-phosphate Dehydrogenase Deficiency Deficiency Research Articles

Acute Haemolysis Precipitating Rhabdomyolysis and Acute Kidney Injury in a Newly Diagnosed G6PD Deficiency: A Case Report

Glucose-6-phosphate dehydrogenase deficiency (G6PD) is a common X-linked genetic condition among Malaysians that have largely caused acute intravascular haemolysis. In G6PD deficient children, the phenomenon of rhabdomyolysis and myoglobinuria is a rare complication as muscle has more resistant to undergo acute myolysis. A 22-month-old Malay child was presented with severe anaemia following with ingestion of large amount of fava beans. He then developed into acute kidney injury together with the laboratory findings of intravascular haemolysis, rhabdomyolysis, and the presence of multi-systems bloods derangement. He showed positive response to hyperhydration, haemodialysis and blood transfusions. Bangladesh Journal of Medical Science Vol. 21 No. 03 July’22 Page: 741-744

Acute Hemolytic Anemia Induced by Levofloxacin in A Woman With G6PD Deficiency: A Case Report

Introduction: Glucose 6-Phosphate Dehydrogenase deficiency (G6PD) is an X-linked recessive disorder recognized as the most prevalent enzyme deficiency around the world. G6PD deficiency has a high prevalence in Iran, especially in the northern regions. As we know, hemolysis in G6PD patients was not reported with levofloxacin previously.
 Case Report: In this report, we introduce a 54-year-old G6PD deficient woman who experienced the symptoms of hemolytic anemia following completion of treatment with levofloxacin.
 Result: After ruling out other causes of hemolysis, by using the Naranjo scale, levofloxacin was considered as a possible cause of hemolysis.
 Conclusion: Though the hemolytic anemia induced by levofloxacin is extremely rare in G6PD deficient patients, drug-induced hemolytic anemia should be considered as one of the differential diagnoses. It would be appropriate to use an alternative antibiotic instead of levofloxacin in a G6PD deficient patient.

Effects of UGT1A1 Polymorphism, Glucose-6-Phosphate Dehydrogenase Deficiency and Deletional (-3.7кb) α-Thalassemia Among Young Nigerians with Sickle Cell Anemia

Several genetic factors modulate the clinical course of sickle cell anemia (SCA), such as the βs-haplotypes, 3.7кb α-globin gene deletions (-α3.7), glucose-6-phosphate dehydrogenase deficiency (G6PD), UGT1A1 polymorphism and influencers of fetal hemoglobin production. While many studies on these modifiers have been conducted among patients in the developed world, little is known about how they impact SCA among Nigerians.We hypothesized that these factors could modulate SCA in the Nigerian population. Hence, we set out to determine whether βs-haplotype, -α3.7deletion, G6PD, and UGT1A1 polymorphism influence the laboratory markers and clinical events in young Nigerians with SCA.The study was conducted among 101 hydroxyurea-naïve SCA patients aged 2-21years, (median 9 years) in steady state, on regular follow up at the pediatric hematology unit of the Ekiti State University Teaching Hospital (EKSUTH), Ado Ekiti, Southwest Nigeria.Molecular analysis were conducted to confirm the diagnosis of SCA by polymerase chain reaction (PCR) and direct sequencing; alpha thalassemia by GAP-PCR; to determine UGT1A1 genotypes by Fragment Analysis; and BS haplotypes and G6PD genotypes by TaqMan SNP genotyping assay at the Hemocentro - University of Campinas, Brazil. Automated analysers were used to carry out hematologic and biochemical analyses. Records of the patients were examined for clinical events and steady state laboratory parameters. Serial abdominal ultrasounds were done as clinically indicated to diagnose gallstones. Institutional review board approval was obtained and the study protocols followed the Declaration of Helsinki as revised in 2000.Four (TA)n alleles (5, 6, 7, and 8) were found with gene frequencies of 0.11, 0.44, 0.40, and 0.05, respectively, grouped into 11 genotypes: TA5/5, 5/6, 5/7, 5/8, 6/5, 6/6, 6/7, 6/8, 7/7, 7/8, 8/8. Low Activity UGT1A1 genotypes (TA7/7, 7/8, 8/8) were found in 25 (24.7%). The Benin/Benin βs-haplotype was found in 94 (93%), Benin/Cameroun 4 (4%), Benin/Bantu 2 (2%), and Benin/Arab 1(1%). Mutation for the African variant of G6PD deficiency (202G>A) was found in 21(20.8%). None had the Mediterranean (563C>T) mutation. The frequency of 3.7 κb α-globin gene deletion was 34 (33.6%) αα /-α3.7 as heterozygous, 7 (7%) -α3.7/-α3.7 homozygous. Additionally, we found one (1%) α-globin triplication (αααanti3.7/αα).There was significant difference in bilirubin levels of the patients when differentiated by the UGT1A1 genotypes according to expected enzyme activity (low > intermediate > high activity with median unconjugated bilirubin levels of 1.8, 0.8, and 0.6mg/dL, respectively, P <0.0001). The presence of either alpha thalassemia or G6PD deficiency or both did not alter this trimodal pattern of bilirubin levels. Asymptomatic gallstone was found in 6 (5.9%) patients aged 10 to 16 years. Five of them had the low UGT1A1 activity genotypes 4 (TA7/7) & 1(TA7/8). The low genotype was significantly associated with gallstone when compared to other genotype groups 5/25 vs 1/76, P=0.0033. Bilirubin levels of patients with gallstone was significantly higher than age & sex matched subjects without gallstone (4.7 vs 1.2mg/dl, p=0.002) suggesting that the pathway to developing hyperbilirubinemia and gallstone is primarily driven by the influence of UGT1A1 genotype of our study cohorts.When we evaluated the influence of -α3.7 deletion, we found that participants with alpha thalassemia had higher frequencies of pain crisis in the preceding one year of the study with median episodes of 3 (range 0-6) vs 0 (range 0-6), P <0.0001. The presence of alpha thalassemia was significantly associated with decreased mean corpuscular volume, mean corpuscular hemoglobin, reticulocyte count and with a higher hemoglobin concentration (P <0.05) However, none of the 6 participants with leg ulcers had alpha thalassemia 0/ 42 vs 6/59 (P=0.039). There were no significant associations of βs-haplotypes and G6PD deficiency with both laboratory parameters and clinical events.In conclusion, our findings confirmed that both alpha thalassemia and UGT1A1 polymorphism influence the laboratory markers and clinical events of young Nigerians with SCA. It appears the influence of UGT1A1 polymorphism outweighs the modest ameliorating effect of alpha thalassemia on hyperbilirubinemia and cholelithogenesis among the patients. DisclosuresFertrin:Alexion Pharmaceuticals: Consultancy.

Association of Hydroxychloroquine use and Hemolytic Anemia in Patients With Low Levels of Glucose-6-Phosphate Dehydrogenase.

Glucose-6-phosphate dehydrogenase deficiency (G6PD) is linked to hemolytic anemia with certain medications and is the most common enzyme deficiency worldwide. Although the American College of Rheumatology does not recommend routine testing for G6PD prior to initiation of hydroxychloroquine (HCQ), the package insert for HCQ does recommend careful use in patients with G6PD deficiency. We identified eligible subjects seen at our tertiary care, urban medical center between 1997 and 2018. Case records were analyzed for G6PD deficiency, HCQ use, length of exposure to HCQ, demographic characteristics, and laboratory evidence of hemolysis. We found 5264 patients who were prescribed HCQ, of which 49.5% (2605 patients) were screened for G6PD deficiency. Of the screened patients, 36 were found to be G6PD-deficient. Of the G6PD-deficient patients, 18 were exposed to HCQ. No evidence of hemolysis was found in these exposed patients. Despite more than 500 months of cumulative exposure time to HCQ, there were no cases of hemolysis. These findings are in line with recently published data and suggest that this interaction is not associated with clinically significant hemolysis in our population of mainly African American and Hispanic patients. Limitations to our study are potential bias due to case review design and lack of prior assessment of episodes of hemolysis before HCQ exposure. A high proportion of our patients were Hispanic, suggesting no increase of adverse events in this subgroup. A larger longitudinal trial would be needed to definitively answer the question of the safety of HCQ in G6PD-deficient patients.

Noninvasive Detection of Hemolysis with ETCOc Measurement in Neonates at Risk for Significant Hyperbilirubinemia

Background: Hemolytic hyperbilirubinemia due to blood group incompatibility or glucose-6-phosphate dehydrogenase deficiency (G6PD) is a common cause of significant hyperbilirubinemia. Hemolysis in a hyperbilirubinemic infant increases the risk of bilirubin neurotoxicity. A new portable device (CoSense) can rapidly detect breath end-tidal carbon monoxide corrected to ambient carbon monoxide (ETCOc). ETCOc levels are surrogate markers of hemoglobin breakdown and bilirubin production. Objective: The aim was to evaluate the association between ETCOc values and hemolysis and its relevance in neonates at risk for significant hyperbilirubinemia. Methods: A prospective study was conducted among newborn infants born at more than 35 weeks and with a birth weight greater than 2,000 g with a G6PD deficiency, blood group incompatibility, or clinical jaundice needing phototherapy during the first 7 days of life. The recruited infants had their breath ETCOc measured twice, first on the day of recruitment and then again on the following day. Results: Fifty infants completed this study. Their mean ETCOc was 1.61 (±0.56) ppm. There was a linear correlation (r = 0.89) between increasing ETCOc values and reticulocyte counts (RC). Sixteen newborns with ABO incompatibility had a significantly higher mean ETCOc of 1.98 ppm (±0.71) as compared to 1.43 (±0.38) ppm in the nonhemolytic hyperbilirubinemia (NHH) group (n = 25) (p = 0.002). This was suggestive of hemolysis as shown by the significantly higher RC of 6.90% (±3.38) compared to 4.68 (±1.26) in the NHH group (p <0.005). Neonates with an ETCOc level ≥1.8 ppm had a higher RC, a lower hemoglobin level, higher serum bilirubin levels, and a rapid rise in serum bilirubin and needed a longer duration of phototherapy. ETCOc values ≥1.8 ppm were suggestive of hemolysis (RC ≥6%), with a sensitivity of 90% and a specificity of 83%. Conclusion: Higher ETCOc values ≥1.8 ppm are suggestive of hemolysis and they are associated with significant hyperbilirubinemia.

Hereditary Hemolytic Anemias Other Than Thalassemia: Single Center Experience

Aim: The aim of this study was to evaluate the demographic information, clinical and hematologic findings and treatment response of patients diagnosed with hereditary hemolytic anemias other than thalassemia at a single center. Materials and Methods: A total of 157 children with a diagnosis of hereditary hemolytic anemia except thalassemia were included. Patients' files were reviewed retrospectively. Demographic, clinical and laboratory characteristics, family history, complications, history of splenectomy and cholecystectomy, splenectomy response, use of chelating agents and other treatments, first transfusion age and transfusion frequency of patients were evaluated. Mean, standard deviation, median and 25-75 percentile values were used when descriptive analysis were presented. Mann Whitney U and Kruskal Wallis Tests were used for nonparametric groups. Pearson Chi Square and Fisher Tests were used when categorical comparisons were made. A value of P &lt;0.05 was considered statistically significant. Results: Of the 157 patients , 101 patients (64,3%) had hereditary spherocytosis, 39 patients had (24,8%) glucose-6 phosphate dehydrogenase deficiency (G6PD), 15 patients had (9,6%) sickle cell anemia and 2 patients had (1.3%) pyruvate kinase deficiency. Sixty-one patients (38,9%) were girls and 96 were boys (61,1%). Median age of diagnosis was 10 months (range 1-188 months). Of 97 patients whom family history was questioned, 63 (64.9%) had family history. Most common complaint at diagnosis was paleness. Eighty-two patients had splenomegaly. Twenty-two patients (14%) had cholecystectomy and 56 patients (35.7%) had splenectomy on follow-up. The most frequent indication for splenectomy was hereditary spherocytosis. Fifty-eight (36.9%) patients required regular transfusion. Mean ferritin level of all was 506.3±1175.0. Patients with pyruvate kinase had the highest ferritin levels. Erythropoietin was used for 1 patient with hereditary spherocytosis in infancy without a response. Ten of 15 patients with sickle cell anemia were using hydroxyurea. Thirteen percent of all were using chelating agents. Conclusion: Hereditary spherocytosis and G6PD deficiency were the most common hereditary hemolytic anemias except thalassemia in our center. Family history was more frequent in hereditary spherocytosis compared to other hereditary hemolytic anemias. Patients with G6PD deficiency were diagnosed earlier than other hereditary hemolytic anemias. Hereditary spherocytosis was the most common indication for splenectomy and eliminated/decreased transfusion requirement in 96%. Patients with other hemolytic anemias had lower iron load compared to thalassemia except pyruvate kinase deficiency patients. Disclosures No relevant conflicts of interest to declare.

Severe neonatal hyperbilirubinemia in the southeast region of Turkey

Severe neonatal hyperbilirubinemia is an important cause of morbidity and mortality in developing countries. The aim was to assess etiologic reasons for development of severe hyperbilirubinemia and define risk factors for exchange transfusion and acute bilirubin encephalopathy (ABE) in Şanlıurfa located in the southeast region of Turkey. An observational cohort study included 115 infants with ≥35 weeks of gestation admitted with diagnosis of severe hyperbilirubinemia in a period of 18 months. Potential risk factors associated with exchange transfusion and development of ABE were analyzed. Among 115 infants, 67 (58.3%) received exchange transfusion and 45 (39.1%) developed ABE. Rh isoimmunization (OR: 24.6, 95% CI = 2.2–271, P = 0.009), glucose-6-phosphate dehydrogenase deficiency (G6PD) (OR: 21.1, 95% CI = 1.8–238.4, P = 0.01), early discharge (OR: 14.4, 95% CI = 4.2–48.9, P ≤ 0.001), and male sex (OR: 4.3, 95% CI = 1.3–14.1, P = 0.02) were independently associated with an increased risk for exchange transfusion. Being a refugee (OR: 6.8, 95% CI = 1.8–25.8, P = 0.005) and G6PD deficiency (OR: 9.9, 95% CI = 1.3–71.9, P = 0.02) were associated with development of ABE. Early discharge, Rh isoimmunization, and G6PD deficiency are significant risk factors for severe hyperbilirubinemia and exchange transfusion. Prevention of early hospital discharges, family education to increase awareness for hazardous effects of hyperbilirubinemia, and early follow-up visits after discharge would reduce the disease burden.

Prevalence of glucose-6-phosphate dehydrogenase deficiency and sickle-cell trait among blood donors: Revisited after 10 years in the same institute

BACKGROUND: Sickle cell anemia and glucose-6-phosphate dehydrogenase deficiency (G6PD) are the most common causes of inherited hemolytic anemia in Saudi Arabia. Due to high prevalence, some blood transfusion services perform routine blood donor screening for hemoglobin S (HbS) and G6PD enzyme assay. This study was conducted to reassess the prevalence of these disorders after 10 years of the last published report from the same institute. In addition, the utility of donor screening for sickle trait status was also reviewed. DESIGN: This cross-sectional study has utilized archived data of all blood donors between April 2016 and June 2016. All blood donors who fulfilled the inclusion criteria for blood donation during the study period were enrolled in this study. They all answered a standardized medical questionnaire and have been clinically examined by the blood bank medical staff as well. MATERIALS AND METHODS: All donors' samples were tested for sickle-cell trait (SCT) by HbS solubility test and capillary electrophoresis and for G6PD enzyme activity by fiuorescent spot test. All investigations were completed within 24 h after blood collection and processed based on the standardized procedures which have been fully accredited by the College of American Pathologists. RESULTS: Of the 2748 blood donors' samples, there were 2701 (98.3%) males and 47 (1.7%) females. SCT was present in 41 (1.49%), G6PD was detected in 80 (2.91%), and 14 (0.50%) donors were positive for both conditions. All the donors with positive results for both conditions were males. CONCLUSION: The utility of donor screening for SCT in the central region of KSA is questionable due to the low prevalence of SCT carrier among blood donors and increase of public awareness about HbS carrier status due to wide implementation of premarital screening program for sickle cell and thalassemia. In the same manner, screening of G6PD deficiency should be restricted only to high-risk recipient such as premature neonates.

The relationship between neonatal factors and involving with glucose-6-phosphate dehydrogenase deficiency (G6PD) and patients' outcome in Fars Province

Introduction: Glucose-6-phosphate dehydrogenase deficiency (G6PD) or fauvism is the most common enzyme deficiency in human, so that 400 million people are living with this disease worldwide. This study aimed to investigate the role of some neonatal factors among newborns suffering from G6PD deficiency and neonatal outcomes associated with this disease. Materials and methods: In this study, two methods including case-control and retrospective cohort regarding some neonatal factors associated with G6PD deficiency were used. These methods were performed on 142 children with this kind of deficiency and 142 healthy infants in the city of Marvdasht during 2013- 2014. The analysis of data was based on chi-square tests, t-test, logistic regression, descriptive statistics and estimation of odds ratios or relative risks via SPSS16 software. Results: Totally 284 newborns including 132 (46.6%)/ 152 (53.4%) boys/girls and mean weight on birth of 3163 ± 471 (gr) were analyzed. Comparison of case and control samples did not show any significant differences between sex and involving with G6PD deficiency but the chance of having a baby with this defect in pregnancy intervals between 6 to 8 years was increased (95% CI: 1- 4.4, OR: 2). Relative risk of jaundice in infected and healthy infants was estimated as 3.73, which demonstrated a statistically significant association (95% CI: 1.33- 10.4). The frequency of low birth weight, birth order and type of delivery was associated with the disease, but their differences were insignificant compared to the healthy group. Conclusion: The results of this study showed that the number of hospitalization is increased due to jaundice in infants with G6PD. There is also an insignificant relation between low birth weight, rank of birth and type of delivery. Thus, it is recommended that other consequences of this deficiency need to be revealed by screening other populations with more samples.

A Novel A1088T Mutation in the Glucose-6-Phosphate Dehydrogenase Gene Detected by RT-PCR Combined with DNA Sequencing.

Human glucose-6-phosphate dehydrogenase deficiency (G6PD) is mostly caused by single nucleotide change in the G6PD gene which leads to single amino acid substitution. Previous trials suggested a few samples had decreased ratio of G6PD/6PGD(<1.00) but no mutation detected by multiple methods. In 138 cases of Chinese children with G6PD deficiency, RT-PCR combined with DNA Sequencing was performed to screen the mutations in the coding region and promoter region of G6PD gene. The mutation detection frequency by this method was 100%, including a novel missense mutation (1088 A>T) and 13 mutations reported before. The novel mutation predicted an Asn-to-Ile substitution at codon 363, which was identified in a male infant patient. The variant caused by this mutation had reduced enzymatic activity, belonging to WHO Class I. Synonymous or missense mutation was not found in the proximalpromoter region of the G6PD gene, which was consistent with earlier findings that G6PD deficiency was not associated with promoter mutations in the G6PD gene. RT-PCR combined with DNA Sequencing could be another alternative for clinically molecular diagnosis of G6PD deficiency.

Glucose-6-phosphate dehydrogenase deficiency in northern Mexico and description of a novel mutation.

Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme pathology in humans; it is X-linked inherited and causes neonatal hyperbilirubinaemia, chronic nonspherocytic haemolytic anaemia and drug-induced acute haemolytic anaemia. G6PD deficiency has scarcely been studied in the northern region of Mexico, which is important because of the genetic heterogeneity described in Mexican population. Therefore, samples from the northern Mexico were biochemically screened for G6PD deficiency, and PCR-RFLPs, and DNA sequencing used to identify mutations in positive samples. The frequency of G6PD deficiency in the population was 0.95% (n = 1993); the mutations in 86% of these samples were G6PD A(-202A/376G), G6PDA(-376G/968C) and G6PD Santamaria(376G/542T). Contrary to previous reports, we demonstrated that G6PD deficiency distribution is relatively homogenous throughout the country (P = 0.48336), and the unique exception with high frequency of G6PD deficiency does not involve a coastal population (Chihuahua: 2.4%). Analysis of eight polymorphic sites showed only 10 haplotypes. In one individual we identified a new G6PD mutation named Mexico DF(193A>G) (rs199474830), which probably results in a damaging functional effect, according to PolyPhen analysis. Proteomic impact of the mutation is also described.

Prevalence and molecular basis of glucose-6-phosphate dehydrogenase deficiency in Afghan populations: implications for treatment policy in the region

BackgroundGlucose-6-phosphate dehydrogenase deficiency (G6PD), an x-linked inherited enzymopathy, is a barrier to malaria control because primaquine cannot be readily applied for radical cure in individuals with the condition. In endemic areas, including in Afghanistan, the G6PD status of vivax patients is not routinely determined so the drug is rarely, if ever, prescribed even though it is included as a recommended treatment in local, regional and global guidelines. This study assessed the prevalence and genotype of G6PD deficiency in Afghan populations and examined the need for routine G6PD testing as a malaria treatment and control tool.MethodsA cross-sectional household survey was conducted using random sampling in five Afghan cities to determine the prevalence of G6PD deficiency in Afghan ethnic groups. Filter-paper blood spots were analysed for phenotypic G6PD deficiency using a fluorescent spot test. Molecular analysis was conducted to identify the genetic basis of the disorder.ResultsOverall, 45/1,436 (3.1%) people were G6PD deficient, 36/728 (5.0%) amongst males and 9/708 (1.3%) amongst females. Amongst males the prevalence was highest in the Pashtun ethnic group (10%, 26/260) while in Tajik males it was 8/250 (3.2%); in Hazara males it was 1/77 (1.3%) and in Uzbek males is was 0/125. Genetic testing in those with deficiency showed that all were of the Mediterranean type (Med-) characterized by a C-T change at codon 563 of the G6PD gene.ConclusionPrevalence of G6PD deficiency in Afghanistan varies considerably by ethnic group and is predominantly of the Mediterranean type. G6PD deficient individuals are susceptible to potentially severe and life-threatening haemolysis after standard primaquine treatment. If the aim of increasing access to radical treatment of vivax is to be successful reliable G6PD testing needs to be made routinely available within the health system.

德宏州0~7岁儿童地中海贫血与G6PD 缺乏症的流行病学调查

目的：了解云南德宏州7岁以下儿童地中海贫血与G6PD缺乏症的现状。方法：血红蛋白病检测：对调查者用日本SysmexKX-21N和迈瑞-2000血细胞分析仪进行血细胞分析，PH8.6缓冲液醋酸纤维薄膜做电泳分析；G6PD缺乏症检测：采用改良葡萄糖6-磷酸脱氢酶(G6PD)测定比值法(手工操作法)进行检测。结果：不同县市和民族地贫检出率不同，潞西市最高51.5%，民族以景颇族最高50.8%。G6PD缺乏症检出率以德昂族最高8.6%(30/349)，其次为阿昌族7.3%(19/261)。结论：云南省德宏州0~7岁以下儿童的地贫和G6PD缺乏症属高发，地贫和G6PD缺乏症的人群地理分布与历史上疟疾流行的地理分布存在着一定的相关性。该调查为云南省德宏州少数民族进行遗传咨询及进行地贫和G6PD缺乏症的预防提供了有价值的基础资料。 Objective: To investigate the carrier rate of thalassemia and G6PD deficiency among the children of 0 - 7 years old in Dehong in YunNan. Method: 2164 samples of children 0 - 7 years old are verified by blood cell automatic analysis, hemoglobin electrophoresis and erythrocyte glucose-6-Phosphate dehydrogenase deficiency (G6PD) diagnos-tic kit. Result: There are different detection rates of thalassemia in different regions and nationalities, the highest region is 51.5% in Luxi, the highest nationality is 50.8% of Jingpo. The relevance ratio of G6PD deficiency of Dehong is 8.6%, ranking first, Achang is 7.3%, ranking second. Conclusion: Thalassemia and G6PD deficiency are high among the children of 0 - 7 years old in Dehong in YunNan. There are certain correlations between the geographic distribution of thalassemia and G6PD deficiency and geographic distribution of malaria in history. The investigation provides valuable basic data for Dehong minorities in Yunnan to conduct genetic counseling and thalassemia and G6PD deficiency pre-vention.

Seizure is a rare presentation for acute hemolysis due to G6PD deficiency. We report a previously healthy boy who presented initially with seizure and cyanosis and subsequently acute hemolysis, due to glucose-6-phosphate dehydrogenase deficiency (G6PD) an

Seizure is a rare presentation for acute hemolysis due to G6PD deficiency. We report a previously healthy boy who presented initially with seizure and cyanosis and subsequently acute hemolysis, due to glucose-6-phosphate dehydrogenase deficiency (G6PD) and probably secondary methemoglobinemia, following the ingestion of fava beans.

Deficiencia de glucosa-6-fosfato deshidrogenasa.Serie de casos clínicos

We describe the laboratory and clinical characteristics of 50 patients with glucose 6 phosphate dehydrogenase deficiency (G6PD). G6PD deficiency represented 1.1% of all the diagnosis made. Coexistence of G6PD with other erythropathy was detected as follow: G6PG/HbS 2 patients and G6PG/hereditary spherocytosis 1 patient. A positive Brewer's test was found in 100% of males but in only 56% of women. Males had a mean enzymatic activity (MEA) of 0.85 ± 0.52 U/g Hb. Women, with positive Brewer's test, showed a MEA of 3.82 ± 1.26 U/g Hb, while the MEA of women with negative Brewer's test was 5.65 ± 2.84 U/g Hb. Genetic counseling and the list of food and drugs potentially harmful was given to all patients. The inclusion of simple screening tests, such as Brewer's test, in the study of anemia, enables us to detect asymptomatic males and carriers in whom this enzymopathy was co-inherited with another erythropathy.

Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali

BackgroundArtemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group.MethodsBlood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene.ResultsThe DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%). The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and G6PD-normal participants were comparable (p > 0.05). After treatment, parasite clearance did not change significantly whether the participants were G6PD deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05).ConclusionsThe presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT.

Frequency of Mediterranean mutation among a group of Saudi G6PD patients in Western region‐Jeddah

Glucose-6-phosphate dehydrogenase deficiency (G6PD), a common human enzymatic defects characterized by extreme molecular and biochemical heterogeneity is found to have a variable frequency in different regions. The molecular basis of polymorphic variants in Saudi Arabia have yet to be fully addressed to. Accordingly, a study was designed to determine the frequency of G6PD gene mutations in G6PD deficient cases. From forty-seven unrelated G6PD-deficient subjects, DNA was extracted individually from peripheral blood samples and exons 6 and 7 of the G6PD gene were amplified by PCR. Mutation analysis was carried out by using conformation sensitive gel electrophoresis (CSGE), followed by direct DNA sequencing. The results showed definite altered CSGE patterns. Two mutations were resolved in exon 6 of G6PD gene; Mediterranean mutation and Sibari mutation, not previously reported so far; while no mutation was detected in exon 7. The frequency of exons 6 mutations responsible for G6PD deficiency (Mediterranean type) is reported for the first time from this region, with a figure of 50.1%. The absence of other mutations in exon 7 causing G6PD deficiency points to the low genetic diversity in the studied population.

Etiology of hemolysis in two patients with hepatitis A infection: glucose-6-phosphate dehydrogenase deficiency or autoimmune hemolytic anemia

We report two children with hemolytic anemia during the course of hepatitis A infection. On admission, the patients had high blood urea nitrogen, creatinine, and uric acid levels, as well as anemia, leucocytosis, and direct and indirect hyperbilirubinemia. Both patients had a glucose-6-phosphate dehydrogenase deficiency (G6PD) and autoimmune antibodies. They were given vitamin K on admission. Inadvertent administration of vitamin K could have been related to an acute reduction in hemoglobin concentration. To prevent renal damage, plasmapheresis with fresh frozen plasma was done to clear bilirubin and plasma hemoglobin. The hyperbilirubinemia responded to plasmapheresis. However, acute tubular necrosis complicated the clinical course in one patient, and several sessions of hemodialysis were required. In conclusion, intravascular hemolysis should be considered in patients with hepatitis A infection, marked hyperbilirubinemia, and anemia. Although hepatitis A vaccination is not yet recommended for routine administration, high-risk patients, including those with a G6PD deficiency, should be vaccinated against hepatitis A.

Determinação da acurácia do método qualitativo da medida da atividade da glicose-6-fosfato desidrogenase

A deficiência de glicose-6-fosfato desidrogenase (G6PD) é um problema de saúde pública que afeta aproximadamente 400 milhões de pessoas no mundo. No mercado, existem vários métodos que medem a atividade da G6PD. Os objetivos deste estudo foram determinar a acurácia do método de Brewer frente a um padrão de referência e estimar a prevalência de deficiência de G6PD na amostra. Foi realizado um estudo transversal de grupo de pacientes internados no HCPA com icterícia a esclarecer, no período de junho de 2004 a maio de 2005. Amostras foram processadas pelo método de Brewer e pelo método de Normalização da Hemoglobina, o qual foi usado como padrão ouro. Foi analisado para atividade da G6PD um total de 173 pacientes. A idade variou de 1 dia a 82 anos, sendo que 66% da amostra possuía até 15 dias de vida. A atividade média e o desvio padrão da G6PD na amostra analisada foi de 17.67± 5,66 U/gHb. A freqüência estimada, pelo padrão ouro, da deficiência de G6PD, foi de 13 (7,7%) pacientes com deficiência parcial ou total, e pelo método de Brewer foi de 14 (8,67%). A sensibilidade do método de Brewer comparada com o método quantitativo da Normalização da Hemoglobina foi de 92,8% e a especificidade foi de 98,7%. A deficiência de G6PD é prevalente em nosso meio. Testes de baixo custo, tais como o teste de Brewer, podem ser utilizados como testes de triagem desta deficiência, principalmente no monitoramento de recém-nascidos que estão sob o risco de desenvolver icterícia neonatal.

Haemoglobinopathies and glucose‐6‐phosphate dehydrogenase deficiency in a Scandinavian perspective

Haemoglobinopathies (mainly thalassaemia and sickle‐cell anaemia syndromes) and glucose‐6‐phosphate dehydrogenase deficiency (G6PD) are globally among the most prevalent single‐genomic diseases. About 3 % of the world's population are heterozygotic for β‐thalassaemia and about 1–2 % for sickle‐cell anaemia, and it is estimated that more than 400 million people are affected by G6PD deficiency worldwide. The disorders are most prevalent in the Mediterranean area, in Asia and Africa. The Scandinavian countries, among others, have seen a boom in immigration during the past 20 years, and therefore migration makes haemoglobinopathies as well as G6PD deficiency increasingly more important from a differential diagnostic perspective in most countries. The purpose of the present special issue of the Journal is to summarize current epidemiological data and elucidate trends and practices in the laboratory diagnosis of these disorders.