Cases Of Glucose-6-phosphate Dehydrogenase Deficiency Research Articles

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.

Chronic nonspherocytic hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency: report of two families with novel mutations causing G6PD Bangkok and G6PD Bangkok Noi

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common hereditary enzymopathies worldwide. Mostly G6PD deficient cases are asymptomatic though they may have the risk of neonatal jaundice (NNJ) and acute intravascular hemolysis during oxidative stress. Chronic nonspherocytic hemolytic anemia (CNSHA) due to G6PD deficiency is rare. In Thailand, one case was reported 40years ago and by biochemical study this G6PD was reported to be a new variant G6PD Bangkok. We, herein, report two families with CNSHA due to G6PD deficiency. In the first family, we have been following up the clinical course of the patient with G6PD Bangkok. In addition to chronic hemolysis, he had three acute hemolytic episodes requiring blood transfusions during childhood period. Multiple gallstones were detected at the age of 27. His two daughters who inherited G6PD Bangkok from him and G6PD Vanua Lava from his wife are asymptomatic. Both of them had NNJ and persistent evidences of compensated hemolysis. Molecular analysis revealed a novel missense mutation 825 G→C predicting 275 Lys→Asn causing G6PD Bangkok. In the second family, two male siblings are affected. They had NNJ and several hemolytic episodes which required blood transfusions. On follow-up they have been diagnosed with chronic hemolysis as evidenced by reticulocytosis and indirect hyperbilirubinemia. Molecular analysis revealed combined missense mutations in exons 12 and 13. The first mutation was 1376 G→T predicting 459 Arg→Leu (known as G6PD Canton) and the second one was 1502 T→G predicting 501 Phe→Cys. We designated the resulting novel G6PD variant, G6PD Bangkok Noi.

G6PD enzyme activity in normal term neonates and adults using OSMMR-D kit with HB normalisation

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common cause of neonatal jaundice in South East Asia. Screening of cord blood for G6PD deficiency by the semiquantitative fluorescent spot test can miss cases of partial G6PD deficiency. Enzymes quantitation using colorimetric method is relatively simple, and able to quantitate the level of the enzymes. We evaluated the method of enzyme quantitation using OSMMR-D kit with haemoglobin (Hb) normalisation and established the normal range of G6PD activity for the normal term neonates and adults. Methods The blood sample was mixed with 75 µL of elution buffer in a well of microplate. The microplate was slowly warmed to 37°C. After incubation for 8 min, the microplate was read at 405 nm for Hb evaluation. Then, colour reagent mixture (OSMMR-D kit, Greece) was added and the microplate was read again at 550 nm at 0 min, then at 10 min. The results are directly expressed in U/g Hb. Blood samples from a total of 106 neonates and 281 adults (aged between 15 and 59 years) were randomly selected for enzyme quantitation. Results All cases showing bright activity with fluorescent spot test demonstrated normal level of G6PD activity with mean of 12.43 U/g Hb for neonates and 9.35 U/g Hb for adults. There was no significant difference in the mean normal G6PD activity between the two racial groups (Malays and Chinese) as well as between the genders. The reference range for normal G6PD activity is 10.15–14.71 U/g Hb for neonates and 6.75–11.95 U/g Hb for adults. Conclusions This study has established the normal range for the G6PD level in normal term neonates and adults. The quantitation of G6PD enzymes using OSMMR-D kit with Hb normalisation was simple since the Hb was analysed simultaneously and the results were reproducible with CV of less than 5%.

Glucose-6-Phosphate Dehydrogenase (G6PD) Variants in Three Minority Ethnic Groups in Central and Northern Vietnam

Community-based surveys for the detection of glucose-6-phosphate dehydogenase (G6PD) deficiency were conducted at three villages in central and northern Vietnam from 2001 to 2006. A total of 799 male individuals belonging to three ethnic groups (Raglai, Pako, and Khomu) were tested for G6PD enzyme activity and 32 G6PD deficient individuals were detected. The prevalence of G6PD deficiency in Raglai, Pako, and Khomu was 2.1% (9⁄438), 7.7% (16⁄208), and 4.6% (7⁄153), respectively. In Raglai, G6PD Viangchan was found to be dominant (8⁄9, 88.9%), followed by G6PD Canton (1⁄9, 11.1%). In Pako, a total of 16 G6PD deficient cases showed G6PD Viangchan variant. All analyzed samples (7⁄7, 100%) showed the G6PD Union variant in the Khomu ethnic group. Our study suggests that the Raglai and Pako people share a common ancestry with Cambodians, Laotians, and Thais. On the other hand, the appearance of G6PD Union among Khomu people suggests that they originate from a different ancestry.

Diabetic ketoacidosis revealing glucose-6-phosphate dehydrogenase deficiency: Description of an adult case

The discovery of an haemolytic anemia after a diabetic ketoacidosis led us to diagnose glucose-6-phosphate dehydrogenase (G6PD) deficiency in a 38-year old male patient. After a favorable course, we reviewed the links between this genetically transmitted enzymatic defect and diabetes mellitus, a public health concern in La Réunion. This description is a rare case of G6PD deficiency revealed after diabetic ketoacidosis in an adult.

Prevalence of G6PD deficiency and knowledge of diagnosis in a sample of previously unscreened Lebanese males: clinical implications

The incidence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Lebanon is estimated at 10 per 1,000 in men and 0.4 per 1,000 in women. A community-based cluster sampling survey was conducted in 15 villages in all areas in Lebanon. The survey found 36 cases of G6PD deficiency among 3,000 men aged 14 years and above, yielding a cumulative incidence rate of 12 per 1,000. Of those 36 cases, 28 (77.8%) knew of their problem since they had already suffered at least one severe anaemia crisis in their childhood following the ingestion of raw green fava beans. The remaining 22.2% were not aware at all of their defect. These findings confirm that G6PD is a common genetic problem in Lebanon. The efficiency of early screening programmes in terms of preventing severe, at times potentially lethal, haemolytic crises is currently being investigated.

The Etiological Analysis of 100 Case of Aged and Non-Hematological Hospitalized Anemia in Southen China.

100 cases of aged non-hematological anemia patients hospitalized in our hospital since July 1, 2000, were analyzed for study on anemia etiology. The mean age was 72.08+/−10.86 (60–90) years (60~ 42; 70~ 39; 80~ 18; 90~ 3) at hospitalization. The etiology of anemia with known showed as followed:Malignant tumor 34: included digestive system malignant tumor 27 (gastric cancer 7, rectal carcinoma 7, colon cancer 6, liver cancer 3, cholangiocarcinoma 2, pencreatic duct cancer 2), lung cancer 3, urinary tract cancer 2, bone sarcoma 2.Iron deficiency anemia 47: digestive tract ulcer 16, hemorrhoid 14. The total number of iron deficiency anemia includes digestive tumors with bleeding.Single nutrition deficiency anemia, macrocytic anemia, i.e. vitamin B12 and/or folic acid deficiency (non-malignant, Non-iron deficiency anemia) 8.Inherited Anemia 10: Thalassemia 6, Glucose-6-phosphate dehydrogenase (G6PD) deficiency 4.Chronic diseases 23: Bone fracture 19, Stroke 18, infection 12, Diabetes 10, Kidney function failure 8, Gynecological bleeding 4.The etiology of anemia is unknown 29: it included some chronic diseases with anemia.Discussion:Incidence of malignant tumor is very high. The incidence of malignancy was 34% in the series of aged anemia. The chance of gene mutation increased as patients' age getting older. When to diagnose aged anemia, we should better to consider that the primary disease is tumor maybe, and look for tumor carefully.Mechanism of anemia in patients with tumor Gastrointestinal tumor with chronic bleeding that can result in anemia. But, there is serious anemia without bleeding in our series. There were some different chronic diseases in 34 cases of tumor. Researchers have discovered that structural and metabolic disorders were detected in mature erythrocytes in patients with and without anemia in stomach cancer. Anemia development pathways were dependent on enhanced hemolysis of circulating erythrocytes and influx of immature cells from the bone marrow.Complication of etiology in aged anemia Etiological diseases of aged anemia is different and complicate. The major of aged anemia has two or more primary diseases. The primary presenting of gastrointestinal tumor maybe is iron deficiency anemia. The tumor with anemia can result from nutritional deficiency at advance. For example, there were vitamin B12 or/and folic acid 8 cases in our aged series. Some anemia patients in our series complicated cardiac disease, stroke, and bone fracture. 2 cases of G6PD deficiency had primarily diagnosed when they suffered from infection at very old age, 70 years or more in these aged anemia. There are 100 million G6PD in whole world, the incidence is very high especially in Africa and South China.Diagnosis should make as soon as possible. Many advanced tumors were incurable. About 20 per cent of patients with carcinoma of the colon or rectum present with metastatic disease. Surgeons are frequently asked to consider resection or other operative procedures in these patients for palliation. But, average survival was 11.2 months for operative patients versus 6.5 months for nonoperative patients (P < 0.05). So we should better discover tumor anemia and differentiate from other benign anemia in the aged anemia as soon as possible for curable section. To pay attention to treat of etiological diseases is very important for aged anemia patients.

Glucose-6-phosphate dehydrogenase deficiency neonatal screening: preliminary evidence that a high percentage of partially deficient female neonates are missed during routine screening

To provide preliminary evidence that the currently employed semiquantitative method of screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency can only detect infants who are totally deficient for G6PD and misses all cases of partial G6PD deficiency. General population: 2150 randomly selected blood samples from the Blood Donation Department, Speliopouleion General Hospital, Athens, Greece. Neonate population: 2000 samples from neonates (50% male; 50% female) in maternity hospitals in the greater Athens area. High risk population: a total of 545 individuals from 133 families in the Athens area, the minimum acceptance criteria being the parents and any brother or sister. Blood specimens from neonates or adults were collected and either spotted and dried on special filter paper (Schleicher and Schull 2992, Darmstadt, Germany) or used in tubes after being heparinised. For the quantitative evaluation of G6PD enzyme activity, the Quantase G6PD screening kit (Quantase Limited, Perth, UK) was used. Quantase G6PD controls (Quantase Limited) were used at three levels of G6PD. These controls are rated at 24, 30, and 37 degrees C. Alternatively, we used the Sigma G6PDH controls (Sigma Chemical Company, St Louis, USA) which are rated at 30 and 37 degrees C. The assay was performed according to the instructions included in the kit with the modification for haemoglobin normalisation. General population: 36 females who were classified as having normal enzymatic activity with the semiquantitative test, were classified as partially deficient with the quantitative test. Neonate population: using the quantitative test, the percentage of G6PD deficient neonates in this population was 5.5%, compared with 3.17% reported in routine screening using the semiquantitative method. High risk population: the quantitative method detected 28 cases of total or partial G6PD deficiency in sisters of males with known total deficiency. The semiquantitative A considerable amount of partially G6PD deficient female neonates (heterozygotes) are undetected and classified as having normal enzymatic activity using the semiquantitative method, which uses a cut off of 2.1 U/g haemoglobin (Hb). The use of a fully quantitative G6PD screening kit is proposed, employing the automated haemoglobin normalisation and a cut off of 6.4 U/g Hb. Any neonate with an activity below this mark should be regarded as G6PD deficient, and all preventive measures should be taken.

Glucose-6-phosphate dehydrogenase (G6PD) variants in Malaysian Chinese Communicated by: Mark H. Paalman Online Citation: Human Mutation, Mutation in Brief #266 (1999) Online http://journals.wiley.com/1059-7794/pdf/mutation/266.pdf

We screened 38 G6PD-deficient male Chinese neonates for known G6PD mutations using established PCR-based techniques. We found 50.0% (19 of 38) were mutation 1376G>T, 34.2% (13 of 38) were mutation 1388G>A, 5.2% (2 of 38 ) were mutation 95A>G and 2.2% (1 of 38) was mutation 1024C>T. In 7% (3 of 38) of the cases the mutations remained uncharacterised. Sixty three percent (24 of 38) of the G6PD deficient neonates had neonatal jaundice with 28.9 % (11 of 38) developing moderate to severe hyperbilirubinemia . The group of neonates with 1388 mutation showed the highest incidence of moderate to severe hyperbilirubinemia requiring phototherapy and/or exchange transfusion respectively. Majority (70%) of the G6PD deficient neonates showed severe enzyme deficiency. However, there was no meaningful association between the level of enzyme activity and the severity of neonatal jaundice. In summary, four mutations account for more than 90% of the G6PD deficiency cases among the Chinese in Malaysia and the pattern of distribution of the molecular variants is similar to those found among the Chinese in Taiwan and southern mainland China. Our findings also suggest the possible association of nt 1388 mutation with severe neonatal jaundice. Hum Mutat 14:352, 1999. © 1999 Wiley-Liss, Inc.

Glucose-6-phosphate dehydrogenase (G6PD) variants in Malaysian Chinese.

We screened 38 G6PD-deficient male Chinese neonates for known G6PD mutations using established PCR-based techniques. We found 50.0% (19 of 38) were mutation 1376G>T, 34.2% (13 of 38) were mutation 1388G>A, 5.2% (2 of 38 ) were mutation 95A>G and 2.2% (1 of 38) was mutation 1024C>T. In 7% (3 of 38) of the cases the mutations remained uncharacterised. Sixty three percent (24 of 38) of the G6PD deficient neonates had neonatal jaundice with 28.9 % (11 of 38) developing moderate to severe hyperbilirubinemia. The group of neonates with 1388 mutation showed the highest incidence of moderate to severe hyperbilirubinemia requiring phototherapy and/or exchange transfusion respectively. Majority (70%) of the G6PD deficient neonates showed severe enzyme deficiency. However, there was no meaningful association between the level of enzyme activity and the severity of neonatal jaundice. In summary, four mutations account for more than 90% of the G6PD deficiency cases among the Chinese in Malaysia and the pattern of distribution of the molecular variants is similar to those found among the Chinese in Taiwan and southern mainland China. Our findings also suggest the possible association of nt 1388 mutation with severe neonatal jaundice.

Molecular characterization of G6PD deficiency in Oman.

Screening of unselected university students in the Sultanate of Oman revealed an overall frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency of 26% in males. Samples from 23 G6PD-deficient individuals (a random sub-sample of the student population), were characterised biochemically and at the molecular level. Of 20 deficient men, 15 had G6PD Mediterranean, 2 had G6PD Chatham, 1 had G6PD A- and in 2 the mutation is not yet known. Of the 3 G6PD-deficient woman, 2 were homozygous for the G6PD Mediterranean mutation and 1 was a genetic compound, G6PD Mediterranean/G6PD A- (the first report of this genotype). Our findings establish that the G6PD Mediterranean mutation accounts for most cases of G6PD deficiency in Oman. The presence of G6PD A- at a polymorphic frequency can be regarded as evidence of significant gene flow from Africa.

Molecular Characterization of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency by Natural and Amplification Created Restriction Sites: Five Mutations Account for Most G6PD Deficiency Cases in Taiwan

We have developed a rapid and simple method to diagnose the molecular defects of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Chinese in Taiwan. This method involves the selective amplification of a DNA fragment from human G6PD gene with specific oligonucleotide primers followed by digestion with restriction enzymes that recognize artificially created or naturally occurring restriction sites. Ninety-four Chinese males with G6PD deficiency were studied. The results show that 50% (47 of 94) were G to T mutation at nucleotide (nt) 1376, 21.3% (20 of 94) were G to A mutation at nt 1388, 7.4% (7 of 94) were A to G mutation at nt 493, 7.4% (7 of 94) were A to G mutation at nt 95, 4.2% (4 of 94) were C to T mutation at nt 1024, 1.1% (1 of 94) was G to T mutation at nt 392, and 1.1% (1 of 94) was G to A mutation at nt 487. These results show that the former five mutations account for more than 90% of G6PD deficiency cases in Taiwan. Aside from showing that G to T change at nt 1376 is the most common mutation, our research indicates that nt 493 mutation is a frequent mutation among Chinese in Taiwan. We compared G6PD activity among different mutations, without discovering significant differences between them.

Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency by natural and amplification created restriction sites: five mutations account for most G6PD deficiency cases in Taiwan

We have developed a rapid and simple method to diagnose the molecular defects of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Chinese in Taiwan. This method involves the selective amplification of a DNA fragment from human G6PD gene with specific oligonucleotide primers followed by digestion with restriction enzymes that recognize artificially created or naturally occurring restriction sites. Ninety- four Chinese males with G6PD deficiency were studied. The results show that 50% (47 of 94) were G to T mutation at nucleotide (nt) 1376, 21.3% (20 of 94) were G to A mutation at nt 1388, 7.4% (7 of 94) were A to G mutation at nt 493, 7.4% (7 of 94) were A to G mutation at nt 95, 4.2% (4 of 94) were C to T mutation at nt 1024, 1.1% (1 of 94) was G to T mutation at nt 392, and 1.1% (1 of 94) was G to A mutation at nt 487. These results show that the former five mutations account for more than 90% of G6PD deficiency cases in Taiwan. Aside from showing that G to T change at nt 1376 is the most common mutation, our research indicates that nt 493 mutation is a frequent mutation among Chinese in Taiwan. We compared G6PD activity among different mutations, without discovering significant differences between them.

Glucose-6-phosphate dehydrogenase variants of papua new guinea

The glucose-6-phosphate dehydrogenase (G6PD) deficiency status of the Papua New Guinea populations is unique from the other populations of the world. We have already presented evidence for the existence of significant biochemical heterogeneity of the G6PD mutants in Papua New Guinea. We have now characterized 10 additional cases of G6PD deficiency in adult males from different regions of Papua New Guinea. Three of these cases were found to be examples of previously described variants (Markham, Salata and Kaluan). Four new variant types have been characterized. Like all previously described G6PD variants from Papua New Guinea these new variants do not exhibit significant levels of activity with the WH037 assay and do not present any evidence of chronic haemolytic anaemia. The biochemical characteristics of these new variants and their distribution in Papua New Guinea will be described.