Cases Of Glucose-6-phosphate Dehydrogenase Deficiency Research Articles

Risk of Hemolytic Anemia in IBD Patients with Glucose-6-Phosphate Dehydrogenase Deficiency Treated with Mesalamine: Results of a Retrospective-Prospective and Ex Vivo Study.

Mesalamine is one of the most-used drugs in inflammatory bowel disease (IBD), especially ulcerative colitis. Regulatory agencies have listed mesalamine as an unsafe drug in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency based on the risk of hemolysis, although scientific evidence is lacking. The occurrence of acute and/or chronic hemolytic anemia in IBD patients with G6PD deficiency exposed to mesalamine was evaluated. In this multicenter study, IBD patients with G6PD deficiency (cases) receiving mesalamine were retrospectively evaluated for acute, and prospectively for chronic, hemolysis. The presence of hemolytic anemia was based on red blood cell and reticulocyte count, hemoglobin, lactate dehydrogenase, unconjugated bilirubin, and haptoglobin levels. Cases were compared with controls (IBD patients with normal G6PD). A total of 453 IBD patients (mean age 52.1 ± 16.0 years; 58.5% female) were enrolled. Ulcerative colitis was present in 75% of patients. G6PD deficiency was detected in 17% of patients. Oral mesalamine was used in 67.9% of ulcerative colitis and in 32.4% of Crohn's disease cases. None of the 78 IBD patients with G6PD deficiency receiving mesalamine underwent hospitalization or specific treatment for acute hemolytic anemia. Relevant differences in chronic hemolysis markers were not observed in 30 cases compared with 112 controls receiving mesalamine (≤4500 mg/day). Marker modifications were also observed in mesalamine-free cases, consistent with the basal rate of erythrophagocytosis in G6PD deficiency. Ex vivo experiments showed the release of methemoglobin by G6PD deficient RBCs upon mesalamine challenge, only above 2.5 mg/mL, a concentration never reached in the clinical setting. This study provides, for the first time, evidence that mesalamine is safe in G6PD deficiency at a dosage of up to 4500 mg/day.

A retrospective study on newborn screening for metabolic disorders.

The process of testing newborn infants for hormonal, genetic, metabolic, and other disorders is known as newborn screening (NSB). Newborn screening is essential for detecting, diagnosing, and treating disorders that could save serious consequences for a newborn's health. Congenital Hypothyroidism (CH), Cystic Fibrosis (CF), Glucose-6-phosphate dehydrogenase (G6PD) deficiency, and Profound Biotinidase deficiency (BD) are common disorders in India. A retrospective analysis of the results of NBS by Cord blood spots was performed at the department of Obstetrics and Gynecology, 7 Airforce Hospital, Kanpur, Uttar Pradesh, from June 2022 to September 2022. During this period, 26 newborns were screened for four disorders, including CH, CF, G6PD deficiency, and BD. In this investigation, no cases of CH, CF, G6PD deficiency, or BD were found to be positive. The results of the current data provide a distinct opportunity to investigate the birth prevalence of inborn metabolic disorders in the area close to the city of Kanpur.

Peripheral blood smear diagnosis of G6PD deficiency in an 83-year-old man.

An 83-year-old male was admitted to the emergency department for abrupt onset of jaundice and asthenia. Vital signs were in range, and physical examination was unremarkable except for jaundice and hyperchromic urine. Full blood count on admission showed his hemoglobin concentration to be 81 g/L with no alteration in white blood cell (WBC) or platelets count. Biochemical tests were significant for high bilirubin level 417.07 μmol/L (indirect bilirubin 369.53 μmol/L) and abnormal lactate dehydrogenase level 1520 μmol/L. The hypothesis of hemolytic anemia was confirmed by further laboratory tests, which showed undetectable haptoglobin and increased reticulocyte count 196 × 109/L. Direct and indirect Coombs tests were both negative, suggesting a Coombs-negative hemolytic anemia. A first blood smear did not show schistocytes and the coagulation profile was in order. Medical history was negative for oxidant drugs assumption, prosthetic heart valves, and liver and kidney diseases. Chest radiography was normal, and a complete abdominal echography did not show hepatomegaly or splenomegaly. Meanwhile, the patient clinical course was complicated by pain and tightness in the chest and dizziness and an electrocardiogram was compatible with a non-ST-segment elevation myocardial infarction. A new set of lab tests showed severe anemia with 66 g/L of hemoglobin, and the patient undergone blood transfusion. In the suspicion of a hemolytic crisis in the context of glucose-6-phosphate dehydrogenase (G6PD) deficiency, an accurate anamnesis was collected and the patient confirmed the assumption of fava beans 3 days earlier after a long time. G6PD levels could not be assessed overnight, but a second blood smear was significant for bite, blister, and ghost cells (Figure 1 A and B), which are findings compatible with G6PD deficiency. Testing for G6PD was performed as soon as available and it revealed a significant G6PD deficiency (2.7 U/g Hb, normal range 8–14 U/g Hb, overestimated because of low Hb concentration). This is a case of G6PD deficiency diagnosed in 83-yer-old patient with no previous similar event in an unfavorable setting (emergency department by night). It highlights the necessity of high clinical suspicion of G6PD deficiency in the context of Coombs-negative hemolytic anemia, even in elderly patients. It is worth noting that different species of fava beans have a different capacity in inducing oxidative stress. Lastly, blood smear can still provide useful morphological data in supporting the diagnosis, regardless the immediate availability of G6PD test. Fabio Giglio conceived the study; D. Sannipoli, D. T. Clerici, and Fabio Giglio provided all clinical and hematological data; A. Boletini and P. Ronchi performed and analyzed morphology; D. Sannipoli and Fabio Giglio wrote the paper. All authors approved the paper. The authors declare no conflict of interest. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Glucose-6-phosphate dehydrogenase deficiency screening and gene analysis in blood donors of Guangdong province

ABSTRACT Objectives The characteristic of glucose-6-phosphate dehydrogenase (G6PD) deficiency is red blood cell (RBC) destruction in response to oxidative stress. Patients requiring RBC transfusions may simultaneously receive oxidative medications or have concurrent infections, both of which can induce hemolysis in G6PD-deficient RBCs. We intend to investigate the incidence of G6PD deficiency in voluntary blood donors and to evaluate the transfusion risk associated with G6PD deficiency in Guangdong province. Methods G6PD enzyme was analyzed in 3042 donors and gene mutations were genotyped in G6PD-deficient samples. Results The G6PD-deficient prevalence of voluntary blood donors was 6.97% (212/3042), 55.19% blood donors with G6PD deficiency donated blood more than twice. Eighty-five cases of G6PD deficiency were genotyped, and the common types of G6PD mutations were c.1376 G > T, c.1388 G > A, c.95 A > G, c.1024 C > T, and c.871 G > A. Conclusions Due to the high prevalence of G6PD deficiency in Foshan area, we recommended that the screening of G6PD deficiency should be carried out for the regular blood donors to ensure the safety of blood users.

The Reference Levels of Glucose-6-Phosphate Dehydrogenase Enzyme Activity for Infants in Taiwan

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency in Taiwan with incidence of 1.8-2.1%. Nationwide newborn screen has been implemented since 1987. To assess the lacking reference levels of G6PD enzyme activity between 7 to 90 days old infants, infants visited National Taiwan University Hospital Hsin-chu Branch from January 1, 2016 to June 30, 2017 were enrolled. G6PD mutation genotyping were carried out by using the Agena MassARRAY system (Agena, San Diego, CA), containing 21 mutations: c.95A>G, c.371A>G, c.392G>T, c.487G>A, c.493A>G, c.517T>C, c.519C>G, c.519C>T, c.592C>T, c.835A>T, c.835A>G, c.871G>A, c.1004C>A, c.1004C>T, c.1024C>T, c.1311C>T, c.1360C>T, c.1376G>T, c.1387C>T, c.1388G>A and c.1365-13T>C.Total 448 cases were studied. Assuming the newborn screen and gene mutation reports are compatible, 24 cases with mismatch reports were excluded. Finally, 424 cases were enrolled, 60.6% (n = 257) were males. The mean age was 37.9 ± 25.0 days old, and mean gestational age was 38 weeks and 6 days. Total 236 cases passed newborn screen and no gene mutation was found. Eighteen (20.5%) samples were collected while infants presented jaundice and the levels were significantly higher than those without jaundice (16.3 ± 4.9 vs. 13.6 ± 3.7 U/gHb, p= 0.014). Therefore, the cases with jaundice were excluded. The rest 218 cases were analyzed and the reference levels of G6PD enzyme activity were 13.6 ± 3.7 U/gHb (95% confidence interval 7.3-25.0 U/gHb), 12.2 ± 3.8 U/gHb (95% confidence interval 8.0-25.2 U/gHb) and 11.4 ± 3.0 U/gHb (95% confidence interval 7.5-19.3 U/gHb) for infants of age 7-30 days old (n = 70), 31-60 days old (n = 65), and 61-90 days old (n = 83), respectively (Table 1). There was no difference between males and females.Total 188 cases failed newborn screen and gene mutation was detected simultaneously. All cases harbored only 1 mutation. The 3 most common mutations, including c.1376G>T (p.R459L), c.1388G>A (p.R463H) and c.95A>G (p.H32R) represented 80.8% (n = 152) in our study. The G6PD level of deficiency cases was significantly lower than that of carrier (Table 2). In G6PD deficiency cases, the G6PD enzyme activity level of cases with c.1388G>A mutation presented the lowest level (p= 0.01). Otherwise, in G6PD carrier cases, the level of cases with c.95A>G mutation tended to present the lowest level (p= 0.056).In conclusion, the levels of G6PD enzyme activity were inversely corrected to age. From our results, we set up the reference levels of G6PD enzyme activity in infants of age between 7 to 90 days old, making diagnosis of G6PD deficiency more precisely in Taiwan. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Mothballs, status dystonicus and critical care: an unusual case of G6PD deficiency

Glucose 6 Phosphate Dehydrogenase (G6PD) is a critical enzyme in the pentose phosphate pathway, a pathway that acts to provide reducing energy to cells. G6PD deficiencies are X-linked inherited disorders, in which the G6PD on red blood cells (RBCs) is defective. This case report will focus on an G6PD deficient individual of Thai descent, Sill, who was exposed to moth balls at an early age. The damage left him with severe dystonic Cerebral Palsy (CP), a permanent movement disorder, causing him to constantly display asymmetric posturing and opisthotonic movements. This article follows Sill through his admission, initially for GJ Tube re-insertion, then for hypoxemia. Sill is seen by several services, who attempt various forms of medication and procedures. This case ends with the insertion of an Intrathecal Baclofen pump; a potential remedy for Sill's current symptoms. Lastly, we discuss the implications of screening for conditions that are typically benign, such as G6PD deficiencies, but can have lethal outcomes.

Favism Induced Methemoglobinemia in G6DP Deficient Patients: Case Series and Review of Literature

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a well-known cause of hemolysis. It has a notable prevalence in African, Asian, and Mediterranean countries. Favism is a common trigger of oxidative stress in G6PD deficient people, which can lead to hemolysis. Additionally, fava bean ingestion can cause methemoglobinemia (MethHgb), an abnormal variation in the Hgb in which the ferrous (Fe2+) iron in heme is oxidized to the ferric (Fe3+) state. It is rare to have both G6PD deficiency and MethHgb secondary to favism at the same time. The first-line treatment for MethHgb is methylene blue. However, in G6PD deficient patients, it can potentiate hemolysis. Methods: We reviewed the literature using PubMed and Google scholar and found 6 cases of MethHgb secondary to favism in patients with G6PD deficiency. We also analyzed two cases which are still unpublished, making a total of 8 cases. Results: All 8 cases were male with median age of 18 years (1 - 56). 1 patient had a prior diagnosis of G6PD deficiency while 7 were newly diagnosed. Median Hgb was 8.3gm/dL (4.6 - 12.5) and median MetHgb was 7.8 % (3.5 - 35). 1 patient received methylene blue, and 4 received Vitamin C. All of the patients recovered and were discharged [Table 1]. Unpublished case 1: A 56-year-old male presented with MethHgb and hemolytic anemia, secondary to fava bean ingestion. Hgb on admission and lowest recorded were 9.9 and 6.5 gm/dL, respectively. He had an SPO2 of 70% on room air and 101.2 % on ABG. Methylene blue administration worsened the hemolysis as he was G6PD deficient but not diagnosed before. He got better with discontinuation of methylene blue and Vitamin C and was discharged on day 5. Unpublished case 2: A 43-year-old male, known case of G6PD deficiency presented with MethHgb and hemolytic anemia, secondary to fava bean ingestion. Hgb on admission and lowest recorded were 12.5 and 7.4 gm/dL, respectively. He had an SPO2 of 82% on room air and 100 % on ABG. He received IV vitamin C and recovered and was discharged on day 4. Discussion: Methemoglobinemia is usually acquired, secondary to oxidative stress in the body, but can rarely be congenital. Enzyme systems such as NADH methemoglobin reductase, NADPH methemoglobin reductase, ascorbic acid, and glutathione reductase systems keep a check on the accumulation of methemoglobin in the blood. However, these mechanisms can be insufficient to counter the conversion of Hgb to MethHgb, consequently promoting an oxidative state in the body. It can be due to the overproduction of methemoglobin (secondary to exposure to certain drugs, chemicals, or food items, but can sometimes be hereditary) or under conversion to Hgb due to unavailable enzyme mechanisms. One of the causes of the inability to counteract methemoglobin can be secondary to G6PD deficiency. Patients with MetHgb have a low oxygen saturation (SPO2) on pulse oximeters but a falsely high SPO2 on arterial blood gasses (ABG). The treatment depends on symptoms and the level of MethHgb. The first step is to remove any possible precipitator if present. Symptomatic patients (and asymptomatic with a level of methemoglobin >30 %) are treated with methylene blue (1-2mg/kg), which is reduced to leuko-methylene blue via NADPH dependent methemoglobin reductase. This, in turn, reduces methemoglobin back to Hgb, correcting the abnormality [Figure 1]. Rarely, patients can present with co-occurrence of MethHgb and G6PD deficiency. In such cases, caution is required while giving methylene blue as they do not have sufficient levels of NADPH to reduce it. Otherwise, a cascade of oxidative hemolysis ensues secondary to underlying G6PD deficiency, resulting in a vicious cycle of further methemoglobinemia. The most frequent cause of this co-occurrence is the ingestion of fava beans, which can simultaneously induce MethHgb and potentiate G6PD deficiency. One of our patients had a history of favism without developing any symptoms. Only this time, he ate fava beans in a larger amount, leading to hemolysis and MethHgb. Conclusion: Favism is a rare cause of the co-occurrence of methemoglobinemia and hemolysis in G6PD deficient individuals. It is vital to identify G6PD deficiency in patients presenting with MethHgb, as the initiation of methylene blue in such individuals can result in a cascade of oxidative hemolysis. A history of fava beans ingestion without any symptoms does not rule out G6PD deficiency, as it is proportional to the number of beans ingested. Disclosures No relevant conflicts of interest to declare.

The modified G6PD deficiency screening test

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which involves the mutation of the G6PD gene on the X chromosome, is the most common enzyme defect in humans. G6PD produces nicotinamide adenine dinucleotide phosphate (NADPH) for red blood cell protection from oxidative stress. Oxidative stress-induced red blood cell hemolysis in G6PD-deficient patients leads to anemia, jaundice, acute renal failure, and kernicterus in newborns. Currently, the fluorescent spot test (FST) is widely used for G6PD deficiency screening. This test detects NADPH production under UV light. This study purposed to modify the G6PD deficiency screening test based on NADPH production and the ability to detect the results of the color change in the color of the reaction. Blood samples of 60 subjects were collected and screened for G6PD deficiency using FST method. All samples were tested with the modified G6PD screening test and the quantitative assay kit. The results from the modified test showed the color red for normal cases, whereas the color brown indicated G6PD deficiency cases. The cutoff value of G6PD activity detected by the quantitative method was less than 2.9 U/gHb for G6PD deficiency. The precision of this study was 100 %. The results of sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the modified test were 100 %, 96.7 %, 100 %, and 96.7 %, respectively. The modified G6PD screening test can be used for the screening of G6PD deficiency in newborns, for support through providing more information, and for self-protection from oxidative stress.

A novel mutation of the ITGB2 gene in a Chinese Zhuang minority patient with leukocyte adhesion deficiency type 1 and glucose-6-phosphate dehydrogenase deficiency

ObjectivesTo explore the clinical and molecular characteristics of a Chinese Zhuang minority patient with leukocyte adhesion deficiency type-1 (LAD-1) and glucose-6-phosphate dehydrogenase deficiency (G6PDD). MethodsRoutine clinical and physical examinations were performed, and patient data was collected and analyzed. Protein expression levels of Itgb2 and glucose-6-phosphate dehydrogenase (G6pd) proteins were assessed by flow cytometry and the glucose-6-phosphate (G6P) substrate method, respectively. Whole exome sequencing was performed to investigate genetic variations of the patient and his parents. ResultsThe patient had fester disease and delayed separation of the umbilical cord at birth. Staphylococcus was detected in the fluid secretion of the auditory meatus of the patient. He exhibited a recurrent cheek scab, swollen hand, and swollen gum. Hematological examination indicated dramatic elevation of leukocytes including lymphocytes, monocytes, neutrophils and eosinophils. A novel homozygous mutation was detected in the ITGB2 gene of the patient, which was determined to be a two nucleotide deletion at the site of c.1537–1538 (c.1537–1538delGT), causing a frameshift of 24 amino acids from p.513 and inducing a stop codon (p.V513Lfs*24). A base substitution mutation was identified at c.1466 (c.1466G>T) of G6PD on chromosome X of the patient, which resulted in an amino acid change from arginine to leucine at p.489 (p.R489L). The patient also showed deficient lymphocyte expression of CD18 (2.99%) and significant downregulation of the G6pd protein. ConclusionsThe patient was diagnosed with G6PDD and moderate LAD-1. The combination of LAD-1 and G6PDD in this case may have been due to the high incidence of genetic disease in this minority ethnic population. Analyzing existing LAD-1 and G6PDD cases from different populations can facilitate disease diagnosis and treatment. Particularly, reporting pathogenic mutations of LAD-1 and G6PDD will be crucial for genetic testing and prenatal diagnosis in an effort to decrease the incidence of these diseases.

Population Based Survey of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency among People Living in Terai Districts of Nepal

Objective: This study was carried out to determine the prevalence of Glucose-6-phosphate dehydrogenase (G6PD) deficiency among population of selected malaria endemic districts in central and eastern terai of Nepal.Methods: Six hundred seventy whole blood samples were collected from the indigenous peoples community, identified based on district public health office records for G6PDd in the past from Jhapa, Morang and Dhanusha districts endemic to malaria, during April to June 2013. Collected blood samples were tested on the sites by using BinaxNow G6PD test kit and CareStartTM G6PD test kits.Results: The G6PD deficiency was found to be in 6.1% and 6.3% in BinaxNow and CareStartTM respectively. In 42 G6PD deficient cases number of male to female ratio was almost equal. Higher proportions of deficient cases were from Rajbanshi and Santhal communities than others. Highest number of deficient cases was in Jhapa followed by Morang and Dhanusha districts respectively.Conclusion: G6PD deficiency in indigenous population group in eastern and central terai are heterogenous. So the testing of G6PD before initiation of radical treatment of Plasmodium vivax infection would be important for reducing the risk of hemolysis following Primaquine (PQ) administration. Rational evidence-based PQ administration may be helpful in contributing towards the elimination of malaria from the country.

Digital epidemiology and geographic mapping of G6PD deficiency: retrospective analytic of trends database existing on the surface web

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited X-linked recessive condition in which the body does not synthesise a sufficient quantity of the G6PD enzyme. Hemolytic anaemic episodes occur following exposure to some medications, foods, or even infections in G6PD-deficient individuals.Aims and Objectives: To assess the digital epidemiology as well as the geographic mapping of G6PD deficiency in the world including countries of the Mediterranean basin.Materials and Methods: This study is primarily based on a digital epidemiological analysis and geographic mapping based on data retrieved from Google Trends database, a very large database, existing on the surface web. A retrospective analysis was carried out for the period from the 22nd of March 2015 to the 24th of January 2016. Trends data will also be contrasted with a collateral data set of a cross-sectional analytic for the same period which was conducted based on the exploration of cases of G6PD deficiency admitted to Jordan University Hospital.Results: Concerning geographic mapping, countries of the Basin of the Mediterranean Sea and the Arabian Gulf accounted for one-third of the entire geographic map at 15.66% and 18.18% respectively. Countries of the Mediterranean basin included Jordan, Italy, Lebanon, Israel, Egypt, Greece, Syria, Cyprus, Tunisia, Algeria, and Morocco. Contributing countries surrounding the Arabian Gulf included Kuwait, Kingdom of Saudi Arabia, Bahrain, Iran, United Arab Emirates, Qatar, and Iraq. The Hashemite Kingdom of Jordan contributed to 2.78% of the global map which accounted for 17.74% of the entire Mediterranean basin. Concerning digital epidemiology, the prevalence was recorded as highest during May 2015 (12.10%), August 2015 (11.17%), and November 2015 (11.28%). Concerning the percentile contribution of monthly records, data were in harmony for those cases admitted to hospital and signals recorded via Google Trends. Both datasets averaged a percentile contribution of approximately 9% per month.Conclusion: This study is the first inferential research on G6PD deficiency based on data from a trends database and parallel data from Jordan University Hospital. Ambitious future research should deploy the use of machine learning for real-time and predictive analytics which will provide an excellent value for public health services and epidemiological studies.Asian Journal of Medical Sciences Vol.9(5) 2018 57-61

The gene spectrum of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangdong province, China

BackgroundG6PD deficiency presents a higher incidence rate in southern China. Many variants of G6PD resulted from point mutations in the G6PD gene, which lead to decrease of enzyme activity. The objective of this study was to analyze the genotype of G6PD deficiency in four regions of Guangdong province. MethodsGenotype of 1756 cases with G6PD deficiency was identified by reverse dot blotting (RDB). Unidentified Genotype of the samples was further ascertained by direct DNA sequencing. Results34 genotype were found in 1756 cases of G6PD deficiency, Canton (c.1376 G>T) and Kaiping (c.1388 G>A) were the most common variants, accounting for more than 63% of G6PD deficiency individuals, and the following mutations were Gaohe (c.95 A>G), Chinese-5 (c.1024 C>T) and Chinese-4 (c.392 G>T). Two rare mutations Orisa (c.131 C>G) and IVS-5 637/638 T del have been discovered in this study. In addition, c.1311 C>T/IVS-1193 T>C polymorphism had a relatively high frequency in the normal G6PD individuals. ConclusionsThis study provided detailed genotypes of G6PD deficiency in Guangdong, and would be valuable for diagnosis and research of G6PD deficiency in this area.

Study of Glucose-6-Phosphate Dehydrogenase Deficiency: 5 Years Retrospective Egyptian Study.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide that causes a spectrum of diseases including neonatal hyperbilirubinemia, acute and chronic hemolysis after exposure to oxidative stress. This five years retrospective study was carried out to study the demographic, clinical and laboratory data of 1000 patients with G6PD deficiency anemia registered in Hematology Unit, Pediatric Department, Tanta University Hospital. Data were collected from patient's files, from November 2011 to November 2016, using the pre-designed questionnaires to obtain the complete history, clinical presentation and laboratory investigations including the complete blood count, red blood cells morphology, liver and renal functions and quantitative assay of G6PD enzyme activity by spectrophotometric method. Males were more commonly affected than females (932 males versus 68 females). The highest prevalence of hemolytic crisis in G6PD deficiency patients was found within the age group of 1-3 years (920 patients; 92%) with mean age of the first presentation of 22.8±15.54 months. Patients presented mainly with pallor (1000 patients; 100%), dark red urine (896 patients; 89.6%) and jaundice (878 patients; 87.8%) after 24-72 hours of exposure to the precipitating factors (mean: 36±17.73 hours). Diets were the most common precipitating factor of hemolysis in patients with G6PD deficiency (834 patients; 83.4% of studied cases) especially fava beans (326 patients; 32.6%) and falafel (194 patients; 19.4%) which were the most common precipitating food products causing hemolysis followed by chick pea (108 patients; 10.8%), broad bean (76 patients; 7.6%), green pea (44 patients; 4.4%), pea nuts (38 patients; 3.8%), lentil (28 patients; 2.8%), and lastly black eyed peas (20 patients; 2 %). Infections were the 2nd most common cause of hemolysis (124 patients; 12.4%) including pneumonia (34 patients; 3.4%), tonsillitis (32 patients; 3.2%), typhoid fever (28 patients; 2.8%), hepatitis A (18 patients; 1.8%) and urinary tract infection (12 patients; 1.2%). Drugs were the least common cause of hemolysis (42 patients; 4.2%) including diclofenac sodium (24 patients; 2.4%), ibuprofen (8 patients; 0.8%), acetylsalicylic acid (4 patients; 0.4%), co-trimoxazole (4 patients; 0.4%) and nitrofurantion (2 patients; 0.2%). There was normocytic normochromic anemia with reticulocytosis and Heinz bodies in pre-transfusion complete blood picture in all studied cases. G6PD assay show marked decrease in enzyme level at time of presentation in all cases with the commonest G6PD enzyme level of 3-4 U/gm Hb (592 patients; 59.2%). G6PD deficiency anemia presented mainly with pallor, dark red urine and jaundice after exposure to certain diets, drugs and diseases and therefore patients with G6PD deficiency should avoid exposure to these precipitating factors of hemolysis. We can also recommend large neonatal screening programs to detect cases of G6PD deficiency before the occurrence of acute hemolysis and molecular studies to detect G6PD enzyme variant in Egypt.

Expanding the clinical and genetic spectrum of G6PD deficiency: The occurrence of BCGitis and novel missense mutation

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway that ensures sufficient production of coenzyme nicotinamide adenine dinucleotide phosphate (NADPH) by catalyzing the reduction of NADP+ to NADPH. Noteworthy, the latter mediates the production of reactive oxygen species (ROS) by phagocytic cells such as neutrophils and monocytes. Therefore, patients with severe forms of G6PD deficiency may present impaired NADPH oxidase activity and become susceptible to recurrent infections. This fact, highlights the importance to characterize the immunopathologic mechanisms underlying the susceptibility to infections in patients with G6PD deficiency. Here we report the first two cases of G6PD deficiency with Bacille Calmette-Guérin (BCG) adverse effect, besides jaundice, hemolytic anemia and recurrent infections caused by Staphylococcus aureus. The qualitative G6PD screening was performed and followed by oxidative burst analysis using flow cytometry. Genetic and in silico analyses were carried out by Sanger sequencing and mutation pathogenicity predicted using bioinformatics tools, respectively. Activated neutrophils and monocytes from patients displayed impaired oxidative burst. The genetic analysis revealed the novel missense mutation c.1157T>A/p.L386Q in G6PD. In addition, in silico analysis indicated that this mutation is pathogenic, thereby hampering the oxidative burst of neutrophils and monocytes from patients. Our data expand the clinical and genetic spectrum of G6PD deficiency, and suggest that impaired oxidative burst in this severe primary immune deficiency is an underlying immunopathologic mechanism that predisposes to mycobacterial infections.

Prevalence of glucose-6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates

Background: The enzyme, Glucose-6-phosphate dehydrogenase (G6PD), deficiency leads to impaired production of reduced glutathione and predisposes the red cells to be damaged by oxidative metabolites, causing hemolysis. Deficient neonates may manifest clinically as hyperbilirubinemia or even kernicterus.Objective: This study was carried out to detect erythrocyte G6PD deficiency in neonatal hyperbilirubinemia.Methods and design: To determine the frequency and effect of G6PD deficiency, this study was conducted on 202 neonates with indirect hyperbilirubinemia. All term and preterm babies up to 13 day of age admitted with clinically evident jaundice were taken for the study. G6PD activity is measured by the UV-Kinetic Method using cellular enzyme determination reagents by spectrophotometry according to manufacturer’s instructions.Results: A total of 202 babies were enrolled in this study. Male babies outnumbered the female (71.3% versus 28.7%). Mean age of the study newborns was 3.75 ± 2.5 days. Eighteen neonates (8.9%) had G6PD deficiency, all are males. One case had combined G6PD deficiency and RH incompatibility. Mean serum total bilirubin was 17.2 ± 4.4 in G6PD deficient cases. There was significant positive correlation between the time of appearance of jaundice in days and G6PD levels in G6PD deficient cases.Conclusion: Neonatal hyperbilirubinemia is associated with various clinical comorbidities. G6PD deficiency is found to one important cause of neonatal jaundice developing on day 2 onwards.

Treatment of pediatric burn patient having glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common red cell enzymopathy found in humans. It clearly has an X-linked recessive inheritance with its prevalence varying from 0% to 27% in a different caste, ethnic, and linguistic groups. This deficiency may result in hemolytic anemia during stress, infection, and use of certain drugs. The use of topical silver sulfadiazine can produce hemolysis in patients having G6PD deficiency. Here, we describe one case successfully treated of pediatric burn of 25% of body surface area who was a known case of G6PD deficiency.

Hyperglycaemia per se does not affect erythrocyte glucose-6-phosphate dehydrogenase activity in ketosis-prone diabetes

AimPreviously, we described patients with ketosis-prone type 2 diabetes (KPD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but no mutation of the G6PD gene. Our present study used two complementary approaches to test whether hyperglycaemia might inhibit G6PD activity: (1) effect of acute hyperglycaemia induced by glucose ramping; and (2) effect of chronic hyperglycaemia using correlation between G6PD activity and HbA1c levels. MethodsIn the first substudy, 16 KPD patients were compared with 11 healthy, non-diabetic control subjects of the same geographical background. Erythrocyte G6PD activity and plasma glucose were assessed at baseline and every 40min during intravenous glucose ramping that allowed maintaining hyperglycaemia for more than 3h. In the second substudy, erythrocyte G6PD activity and HbA1c levels were evaluated in 108 consecutive African patients with either type 2 diabetes or KPD, and a potential correlation sought between the two variables. ResultsThe maximum plasma glucose level after 200min of glucose perfusion was 20.9±3.7mmol/L for patients and 10.7±2.3mmol/L for controls. There was no difference between baseline and repeated G6PD activity levels during acute hyperglycaemia in either KPD patients (P=0.94) or controls (P=0.57), nor was there any significant correlation between residual erythrocyte G6PD activity and HbA1c levels (r=−0.085, P=0.38). ConclusionNeither acute nor chronic hyperglycaemia affects erythrocyte G6PD activity. Thus, hyperglycaemia alone does not explain cases of G6PD deficiency in the absence of gene mutation as described earlier.

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 (<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.

Screening and prevention of neonatal glucose 6-phosphate dehydrogenase deficiency in Guangzhou, China.

We aimed to summarize the results of screening protocol and prevention of neonatal glucose 6-phosphate dehydrogenase (G6PD) deficiency during a 22-year-long period to provide a basis of reference for the screening of this disease. About 1,705,569 newborn subjects in Guangzhou City were screened for this deficiency. Specimens were collected according to the conventional method of specimen acquisition for "newborn dried bloodspot screening", preserved, and inspected. The specimens were studied with fluorescent spot test and quantitative fluorescence assay. Diagnosis was performed using the modified NBTG6PD/6PGD ratio method. Bloodspot filter paper specimens were sent to the laboratory within 24 h via EMS Express, and the G6PD test was performed on the same day. The G6PD deficiency-positive rate was 4.2% in the samples screened using the fluorescent spot test, while it was 5% in case of the quantitative fluorescence assay. Neonatal screening for G6PD deficiency for 11,437 cases (6117 boys and 5320 girls) showed positive results in 481 cases. About 420 cases (318 boys and 102 girls) of G6PD deficiency were confirmed with the modified Duchenne NBT ratio method. The total detection rate was 3.7:5.2% for boys and 1.9% for girls. Quantitative fluorescence assay improved the sensitivity and detection rate. Accelerating the speed of sample delivery by using Internet network systems and ensuring online availability of screening results can aid the screening and diagnosis of this deficiency within 1 week of birth.

Evaluation of G6PD activity and antioxidants status in jaundiced Egyptian neonates

Jaundice with glucose-6- phosphate dehydrogenase (G6PD) deficiency is one of the most common conditions needing medical attention in newborn babies. The aim of the present study was to predict G6PD level and oxidative stress condition among Egyptian jaundiced neonates associated with G6PD deficiency. The study included 60 non-jaundiced neonates and 40 jaundiced cases with G6PD deficiency. All infants were subjected to routine hematological evaluation, total and direct serum bilirubin levels, G6PD assay and oxidative stress markers; malondialdehyde (MDA), glutathione and superoxide dismutase (SOD) levels. Out of the 40 G6PD deficient cases, 62% were males and 37% were females. 15 cases had marked G6PD enzyme deficiency and 25 cases recorded moderate deficiency. Highly increase in bilirubin level was observed in marked G6PD deficient cases than in moderate cases. Hematological indices failed to show evidence of frank hemolysis. There was no significant difference between the marked and the moderate G6PD deficient cases; regarding to the time of appearance of jaundice, frequency of using phototherapy, duration of its application, the need for exchange transfusion and the hematological indices. Oxidative stress markers revealed significant changes in G6PD deficient cases as compared to control group. Neonatal jaundice associated with G6PD deficiency is a condition associated with oxidative stress. Since G6PD deficiency seemed to be the common cause of jaundice in this study, early detection of this enzymopathy for possible jaundice control are recommended in at least preterm infants. Also screening for G6PD deficiency is recommended to define the etiology of hyperbilirubinemia. Key words: Glucose-6- phosphate dehydrogenase, hemolysis, neonate, jaundice, antioxidants.