A-065 Underutilization of Alternate Markers of Hemoglobin A1c in Patients with Altered Red Blood Cell Turnover

Biochemical characterization of erythrocyte glucose-6-phosphate-dehydrogenase from 18 unrelated deficient Saudi Subjects from Al-Hassa and Al-Qatif areas of the Eastern Province was carried out according to WHO procedures. This had led to the identification of one genetically determined common variant, "G6PD Mediterranean". The overall prevalence rate of this deficiency in these areas was determined to be in excess of 42%. None of the subjects studied displayed any sign of favism, a condition usually associated with G6PD Mediterranean, which is characterized by a very low intracellular enzyme activity.

The aim of this study was to estimate the incremental budget impact (IBI) of a rapid diagnostic test to detect G6PDd in male patients infected with Plasmodium vivax in the Brazilian Amazon, as compared with the routine protocol recommended in Brazil which does not include G6PDd testing. The budget impact analysis was performed from the perspective of the Brazilian health system, in the Brazilian Amazon for the years 2013, 2014 and 2015. The analysis used a decision model to compare two scenarios: the first consisting of the routine recommended in Brazil which does not include prior diagnosis of dG6PD, and the second based on the use of RDT CareStart™ G6PD (CS-G6PD) in all male subjects diagnosed with vivax malaria. The expected implementation of the diagnostic test was 30% in the first year, 70% the second year and 100% in the third year. The analysis identified negative IBIs which were progressively smaller in the 3 years evaluated. The sensitivity analysis showed that the uncertainties associated with the analytical model did not significantly affect the results. A strategy based on the use of CS-G6PD would result in better use of public resources in the Brazilian Amazon.

Genetic Analysis in the Tanzania Sickle Surveillance Study (TS3): Modifiers of Sickle Cell Disease and Identification of Hemoglobin Variants

To determine the prevalence of haemoglobin (Hb) variants and glucose-6-phosphate dehydrogenase (G6PD) deficiency in Rwanda. During a two-month period in 2005, 987 cord blood samples were obtained in two hospitals in Kigali and Butare, Rwanda. Screening for sickle cell disorders, other Hb disorders, G6PD deficiency and other rare erythroenzymopathy deficiencies was done using isoelectric focusing techniques and quantitative kinetic assays, respectively. The prevalence of Hb S trait was 2.7% and that of G6PD deficiency was 3.8%. No neonate suffered from a sickle cell disease (homozygous for Hb S or compound heterozygous for Hb S), from another clinically significant haemoglobinopathy, or from pyruvate kinase or glucose phosphate isomerase deficiency. Sickle cell disorders should be considered a public health problem in Kigali and Butare. A systematic neonatal screening programme for those disorders, and to diagnose G6PD deficiency, seems reasonable, but local health priorities must be considered. Adapted management of hereditary sickle cell and G6PD disorders should be available.

Rationale:Glucose 6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells that cause hemolytic anemia. Some anticancer drugs are reported to trigger oxidative stress; however, events of hemolysis are rarely discussed in patients with G6PD deficiency required oncologic treatments.Patient concerns:Here we reported a young woman with G6PD deficiency safely undergoing breast cancer treatment.Diagnosis:A 29-year-old patient was diagnosed with advanced cancer of the right breast with tumors positive for hormone receptor and human epidermal growth factor receptor 2.Interventions:The patient received chemotherapy with doxorubicin, cyclophosphamide, and docetaxel. During the administration of docetaxel, trastuzumab was concurrently administered and was continued after the completion of docetaxel. The patient underwent adjuvant radiotherapy; meanwhile, tamoxifen was administered as adjuvant endocrine treatment.Outcomes:The treatment process was smooth. There was no evidence of hemolytic anemia. Except for hot flushes, the patient lives without remarkable side effects from ongoing or previous treatments.Lessons:Some patients have both G6PD deficiency and malignancy in a geographic area with relatively high incidence of the enzymatic disorder and certain types of cancer. We suggest that our report can contribute to the concern regarding the safety of patients with G6PD deficiency undergoing cancer treatment.

Glucose-6-Phosphate Dehydrogenase Deficiency in Blood Donors Is Associated with Decreased Post-Transfusion Red Cell Recovery

Objectives: Sickle cell anemia (SCA) and glucose-6-phosphate dehydrogenase (G6PD) deficiency are the most common inherited red blood cell (RBC) disorders. The aim of this study was to determine, compare, and correlate G6PD activities with hematological parameters in SCD patients with deficient and non-deficient G6PD and healthy controls in Sana'a, Yemen. Materials and Methods: This cross-sectional study included 150 SCD patients (SCA = 84; SCT = 66) and 150 controls who attended some hospitals in Sana’a from April to June 2022. Five milliliters of venous blood were used for the estimation of CBC and G6PD activity. Data were analyzed using SPSS version 26 software. Results: The SCD patients had significantly lower Hb, PCV, and RBC and higher reticulocytes than controls (P ˂ 0.020). The SCA patients were significantly lower in Hb, PCV, and MCHC and higher in reticulocytes than SCT. G6PD deficiency was found in 26% of the SCD patients, and it was more prevalent in SCA than in SCT and in males than in females. The deficient patients had significantly lower Hb and PCV and higher reticulocytes than non-deficient patients. G6PD activity was found to be positively related to Hb and PCV. Conclusion: G6PD deficiency was more common in SCA patients and had an impact on hematological parameters, which could lead to increased RBC hemolysis. As a result, screening SCA patients for G6PD levels during diagnosis and treatment is advised.

After completing this article, readers should be able to: 1. Explain methods of preventing the hyperbilirubinemia caused by glucose-6-phosphate dehydrogenase (G6PD) deficiency. 2. Compare and contrast the correlation between hemolysis and serum bilirubin levels in healthy infants and those who are G6PD-deficient. 3. Describe the role of deficient bilirubin conjugation in the pathogenesis of G6PD deficiency-associated neonatal hyperbilirubinemia. 4. Define the risk for neonatal hyperbilirubinemia in female G6PD-deficient heterozygotes, G6PD-deficient homozygotes, and hemizygote males. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a commonly occurring X-linked genetic enzyme defect, is notorious for its association with acute hemolytic crises occurring in response to a frequently identifiable trigger (favism). Another potentially devastating danger of this condition is severe neonatal hyperbilirubinemia with its accompanying bilirubin encephalopathy, kernicterus, and death. Far from being a condition limited to historical time epochs and developing countries, G6PD deficiency-associated kernicterus still is seen in modern times. Indeed, among 80 infants from 21 states in the United States documented in a pilot Kernicterus Registry between 1984 and 1998, 18 (22.5%) were reported to have G6PD deficiency. Furthermore, Maisels recently listed G6PD deficiency among the 10 factors that are associated most commonly with an increased risk of nonhemolytic jaundice. Because of the association with favism, G6PD-associated hyperbilirubinemia traditionally has been regarded as hemolytic in origin. However, recent research has shown that although acute hemolysis does play a role, its contribution in many cases may be smaller than previously thought. The emphasis now has been placed on decreased bilirubin conjugation, with promoter polymorphism for the gene for the bilirubin conjugating enzyme, UDP glucuronoslytransferase 1A1 (UGT1A1), being a major factor in production of the icterus. In this review we highlight key aspects of the pathogenesis of this type of hyperbilirubinemia, explain the relevance of the condition, and describe a particularly problematic group that has a recently recognized high incidence of …

Glucose 6-phosphate dehydrogenase (G6PD) deficiency, the most common inherited enzymopathy, can affect HbA1c levels and the diagnosis of type 2 diabetes. This cross-sectional study aimed to investigate the association between G6PD deficiency, its common mutations (G6PD ViangchanG871A, G6PD MahidolG487A) and HbA1c levels in a Thai cohort. Blood samples from 1007 healthy hospital staff were collected during annual health checkups. Individuals with diabetes, diabetes medication use and conditions affecting erythrocyte turnover were excluded. HbA1c levels were measured by enzymatic assay and HPLC, while fasting plasma glucose (FPG) and haematological variables were obtained from checkup records. Fructosamine levels and G6PD activity (classified as deficiency, intermediate, normal) were measured by spectrophotometric assay. Genotyping was performed using TaqMan SNP, PCR-Restriction Fragment Length Polymorphism (RFLP) and Sanger sequencing. Prediabetes and diabetes were diagnosed based on two abnormal results from FPG and HbA1c at the same time, following the modified ADA criteria. Optimal HbA1c cutoffs were determined using receiver operating characteristic curve analysis with bootstrapping in RStudio, optimising Youden's index and the harmonic mean of sensitivity and specificity. HbA1c levels were significantly lower in individuals with G6PD deficiency (25.68 mmol/mol [4.50%] by enzymatic assay; 27.33 mmol/mol [4.65%] by HPLC; n=28; p<0.001) compared with those with normal G6PD levels (34.05 mmol/mol [5.27%] by enzymatic assay; 36.61 mmol/mol [5.50%] by HPLC; n=492). Similarly, individuals with G6PD ViangchanG871A (29.46 mmol/mol [4.85%] by enzymatic assay; 31.15 mmol/mol [5.00%] by HPLC; n=52; p<0.001) and G6PD MahidolG487A (28.63 mmol/mol [4.77%] by enzymatic assay; 31.15 mmol/mol [5.00%] by HPLC; n=15; p<0.001) had significantly lower HbA1c levels. HbA1c levels positively correlated with G6PD activity (r=0.208, p<0.001 by enzymatic assay; r=0.211, p<0.001 by HPLC). The optimal HbA1c cutoffs for predicting prediabetes in participants with G6PD mutation were 33 to <42 mmol/mol (5.2% to <6.0%) by enzymatic assay (sensitivity 70%; specificity 88.64%; accuracy 86.74%) and 34 to <43 mmol/mol (5.3% to <6.1%) measured by HPLC (sensitivity 72.73%; specificity 86.21%; accuracy 84.70%). For diabetes, the optimal cutoffs were ≥42 mmol/mol (≥6.0%) by enzymatic assay (sensitivity 100%; specificity 97.92%; accuracy 97.96%) and ≥43 mmol/mol (≥6.1%) by HPLC (sensitivity 100%; specificity 96.88%; accuracy 96.94%). Using the mutation-specific HbA1c cutoffs resulted in the proportion of individuals being diagnosed with diabetes remaining the same but the proportion diagnosed with prediabetes rose from 8.2% (ADA criteria) to 18.4% using enzymatic assay and from 9.2% to 21.4% using HPLC. HbA1c levels were positively correlated with G6PD activity, with individuals carrying G6PD ViangchanG871A and G6PD MahidolG487A exhibiting significantly lower HbA1c levels. Our findings highlight the need to consider G6PD deficiency and G6PD mutations when using HbA1c to diagnose type 2 diabetes in Southeast Asian populations.

Does G6PD deficiency cause further damage to red blood cells of patients with sickle cell anaemia?

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell disease (SCD) cause hemolysis, often occurring in individuals of African descent. These disorders co-occur frequently, and possibly interact, altering clinical outcomes in SCD. However, epidemiological investigations of SCD with G6PD deficiency have produced variable results. This contribution reviews the available data about the interaction of G6PD deficiency and SCD. Overall, G6PD deficiency contributes few, if any, effects to laboratory values and clinical outcomes in SCD patients, but may impact transfusion efficacy. This observation is most likely because of the relatively increased G6PD activity in the young red blood cell (RBC) population seen in SCD patients with or without G6PD deficiency. In addition, G6PD deficiency possibly interacts with other genetic modifiers, such as α thalassemia, hemoglobin F levels and SCD haplotype. Although G6PD deficiency is relatively common, it does not appear to clinically impact patients with SCD. Nonetheless, it is important to evaluate G6PD status in patients with SCD to avoid the use of medications that may cause hemolysis. Future studies evaluating the clinical impact of transfusions from G6PD-deficient RBC donors would be of the greatest benefit to the current literature.

Background and Objectives Sickle cell anemia (SCA) and glucose-6-phosphate dehydrogenase (G6PD) deficiency are both hereditary diseases of the red blood cells that cause hemolysis. The impact of the interaction of both conditions on the clinical and laboratory presentations of the affected persons is sparse. This study, therefore, correlated G6PD activity with disease severity in persons with SCA by comparing disease severity in G6PD-deficient SCA persons with those with normal G6PD activity. Methodology This cross-sectional study was conducted in the department of Haematology and Blood Transfusion of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. G6PD activity, SCA disease severity, and hematological parameters including reticulocyte counts and Heinz body estimation, bilirubin, and aspartate transaminase were estimated in 67 SCA persons. The results were compared between SCA persons with G6PD deficiency and those with normal enzyme activity. Results The prevalence of G6PD deficiency was found to be 23.9%. The G6PD-deficient SCA patients included 4 (25.0%) males and 12 (75.0%) females. G6PD deficiency was significantly higher in females ( P = .047). There was no significant difference in disease severity scores between G6PD-deficient and G6PD-nondeficient SCA patients. However, G6PD-deficient persons reported significantly higher episodes of severe vasoocclusive crisis (VOC) per annum ( P = .048). The hematological and biochemical parameters were similar between G6PD-deficient and G6PD normal SCA persons except that the G6PD-deficient SCA persons have significantly higher reticulocyte response ( P = .001). There was no correlation between disease severity resulting from reduced G6PD activity and Heinz body formation in SCA persons in the steady state. Conclusion G6PD deficiency significantly contributes to recurrent painful vasoocclusive crisis in SCA persons in the steady state.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of this study is to evaluate the risk factors associated with hyperbilirubinemia in infants from the western part of Guangdong Province, and to assess the contribution of G6PD deficiency to neonatal jaundice. The term infants with neonatal hyperbilirubinemia in People's Hospital of Yangjiang from June 2018 to July 2022 were recruited for the retrospective analysis. All the infants underwent quantitative detection of the G6PD enzyme. The etiology was determined through laboratory tests and clinical manifestations. Out of 1,119 term infants, 435 cases presented with jaundice. For the etiology analysis, infection was responsible for 16.09% (70/435), G6PD deficiency accounted for 9.66% (42/435), of which 3 were complicated with acute bilirubin encephalopathy), bleeding accounted for 8.05% (35/435), hemolytic diseases accounted for 3.45% (15/435), and breast milk jaundice accounted for 2.53% (11/435). One case (0.23%) was attributed to congenital hypothyroidism, multiple etiologies accounted for 22.3% (97/435), and 35.63% (155/435) were of unknown etiology. Of the jaundiced infants, 19.54% (85/435) had G6PD deficiency, while only 10.23% (70/684) of non-jaundiced infants had G6PD deficiency; this difference was found to be statistically significant (P < 0.001). Furthermore, the hemoglobin levels in the jaundiced infants with G6PD deficiency (146.85 ± 24.88 g/L) were lower than those without G6PD deficiency (156.30 ± 22.07 g/L) (P = 0.001). 65 jaundiced infants with G6PD deficiency underwent G6PD mutation testing, and six different genotypes were identified, including c.95A > G, c.392G > T, c.1024C > T, c.1311C > T, c.1376G > T, c.1388G > A, c.871G > A/c.1311C > T, c.392G > T/c.1388G > A, and c.1376G > T/c.1311C > T.65iciency. In newborns in Yangjiang, G6PD deficiency, infection, and neonatal hemolytic disease were identified as the main causes of hyperbilirubinemia and acute bilirubin encephalopathy. Specifically, Hemolytic factors in infants with G6PD deficiency may lead to reduced hemoglobin and increased bilirubin levels in jaundiced infants.

Incidence of Hemolytic Events after Exposure to Triggering Medications in Pediatric Patients with G6PD Deficiency

Do tribal communities show an inverse relationship between sickle cell disorders and glucose-6-phosphate dehydrogenase deficiency in malaria endemic areas of Central-Eastern India?