Glucose-6-Phosphate Dehydrogenase Deficiency in Greece

The glutathione stability of red cells was estimated in 40 patients duringacute hemolysis induced by fava beans. There were wide individual differences but in all cases except one (Case 18) the post-incubation GSH fell tolevels below 40 mg. per cent packed RBC which is the lower normal limit.

The GSH stability on 44 mothers and 37 fathers gave results consistent withthe genetic hypothesis that in male patients the mother is the carrier of thebiochemical defect, while in female patients both parents are carriers, since,as a rule, only female homozygotes suffer from hemolytic episodes. However,in only 77.7 per cent of the mothers could the biochemical defect be proved bythis method.

The Motulsky test was performed in 30 of the 40 patients. It gave abnormaldecolorization times in 25 or 83 per cent of the cases. This test is thereforevaluable for diagnosing "sensitivity" during a hemolytic episode; it is, nevertheless, less sensitive than the GSH stability method.

The Motulsky test was also performed on 31 mothers, 18 fathers and 8siblings. It proved to be unreliable in the detection of female heterozygotes.

G-6-PD deficiency is widely disseminated in Greece; it is, however, notevenly distributed throughout the country.

The highest frequency of G-6-PD deficiency found so far in males was about3 per cent; the lowest was 0.7 per cent.

Submitted on August 1, 1960 Accepted on April 21, 1961     

Red Cell Glucose-6-Phosphate Dehydrogenase Deficiency in Finland

Severe red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency has been found in an ‘aboriginal’ Finnish family. 2 male and 9 female carriers of the variant G-6-PD were studied. The genetic pattern is consistent with x-linked recessive inheritance and the defect is associated with drug (primaquine) induced haemolysis. This was demonstrated by enzyme deficient red cell (⁵¹Cr-labelled) survival studies on a normal volunteer recipient. In addition, one of the hemizygotes studied had a slight chronic nonspherocytic haemolytic disorder. The partially purified enzyme had many of the characteristics of G-6-PD Mediterranean. The occurrence of this G-6-PD Mediterranean type variant in the Finnish population, which differs greatly from Mediterranean ethnic groups, as well as the association of slight chronic haemolysis with severe G-6-PD deficiency is discussed.     

Glucose-6-Phosphate Dehydrogenase Deficiency in Maltese Newborn Infants

S ummary . A survey was carried out to establish the incidence of erythrocyte glucose-6-phosphate dehydrogenase deficiency in newborn infants in the Maltese islands. Of the infants born during the period of the survey 28.7% were tested: 1147 samples were obtained from male and 1016 samples from female infants. Some degree of enzyme deficiency was detected in 5.1% of the samples, and 1.0% were completely enzyme deficient; 5.8% of the male infants and 4.1% of the female infants were enzyme deficient, but only 1.5% of the males and 0.4% of the females were completely deficient. The results are compared with those of a previous survey carried out on the child and adult populations of the islands. G-6-PD deficiency was not found in association with the foetal haemoglobin variant Hb F(Malta).     

Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Jaundice in Jamaica

Glucose-6-phosphate dehydrogenase (G6PD) deficiency was detected in 16 (69.6%) of a group of 23 neonates who had unexplained moderate or severe jaundice. This proportion is significantly more than the 9.4% observed or the 22.2% expected in Jamaican neonates who are not moderately or severely jaundiced (P less than 0.003), and significantly more than the 12.6% observed or the 21.0% expected in older Jamaican children and adults (P less than 0.003). Phenobarbitone therapy and phototherapy reduced the need for exchange transfusion but this was necessary in eight patients. Two babies developed kernicterus and one died. On the other hand, only two of 21 neonates who were identified as G6PD deficient at birth subsequently became moderately or severely jaundiced, and this could be attributed to other causes in both cases. These findings indicate that apparently spontaneous neonatal jaundice is important in infants who have the G6PD A--enzyme. However, the jaundice is probably precipitated by unknown factors to which the G6PD deficient neonate is more susceptible than the infant who is not G6PD deficient. THere is also a slightly increased incidence of G6PD deficiency in neonates who develop jaundice because of ABO or Rh(D) iso-immune disease, infection or prematurity.     

Platelet-Function Studies in Patients with Glucose-6-Phosphate Dehydrogenase Deficiency

S ummary . Tests of platelet function were carried out in 17 patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Despite the clinical absence of defective haemostasis impaired platelet function was observed in all patients studied. This consisted of reduced platelet-factor 3 (PF 3) availability, a reduced prothrombin-consumption time, and/or reduced platelet retention in a glass bead column. PF3 assay of freeze-thawed platelets demonstrated that this reduction of PF3 availability represents a true deficiency rather than defective release. Platelet aggregation with ADP, collagen and adrenaline was normal. These findings suggest that G6PD deficiency, which leads to impaired NADPH production, may cause reduced fatty-acid and phospholipid synthesis by the platelets resulting in PF3 deficiency. The normal platelet aggregation suggests that energy derived from the hexose-moaophospliatc shunt is not essential for this function.     

Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency among Jordanians

Background/Aims: In Jordan, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a significant health problem, and the incidence was reported to be about 3.6%. The aims of this study are to investigate the most common molecular mutations of the G6PD gene among Jordanians in northern Jordan and to examine the correlation between the genotype and phenotype of this enzyme deficiency. Methods: Seventy-five blood samples were collected from patients attending King Abdullah University Hospital and Princess Rahma Teaching Hospital. The G6PD gene was scanned for mutations using a DNA sequencing technique. Results: Our results showed 11 variations (7 exonic and 4 intronic) as follows: c.202 G>A (rs1050828), c.376 A>G (rs1050829), c.404 A>C (CM962574 single-nucleotide polymorphism), c.542 A>T (rs5030872), c.563 C>T (rs5030868), c.1003 G>A (rs5030869), c.1311 C>T (rs2230037), c.486-90 C>T, c.486-60 C>G (rs2515904), c.770+175 C>T (rs2515905) and c.1311 C>T (rs2230037). Among these, G6PD Mediterranean (c.563 C>T) was the most common in our patients, with a frequency of 76.2%, followed by G6PD A- (c.202 G>A + c.376 A>G) with 19%, and an equal frequency of 1.6% was found for G6PD Chatham (c.1003 G>A), G6PD Santamaria (c.542 A>T + c.376 A>G) and G6PD Cairo (c.404 A>C). Conclusion: This is the first report of G6PD Santamaria and Cairo among our Jordanian population.     

Glucose-6-Phosphate Dehydrogenase Deficiency in Saudi Arabia: A Survey

A survey of red cell G-6-PD deficiency has been conducted among 1296Saudi subjects. Thirteen per cent of randomly selected male subjects and 2.4per cent of the females tested were found to be G-6-PD deficient. In this study,the screening test employed did not detect female (partially G-6-PD deficient)heterozygotes. The deficiency appeared to be localized to the oasis of theEastern province, and in village studies a very high incidence was found inmale children from the Qatif and Al-Hasa oases. The geographic limits ofG-6-PD deficiency correspond precisely to the areas known to be hyperendemic for malaria in previous years. However, the population group affected represents a distinct minority in terms of religious and cultural tradition, and anthropometric type. In Saudi Arabia, falciparum malaria does notappear to be the only significant factor determining marked regional differences in the incidence of G-6-PD deficiency: this genetic marker is essentially confined to the Shiite muslim population. The Sunni population, regardless of its proximity to areas of endemic falciparum malaria, has a lowincidence of G-6-PD deficiency.

Submitted on October 17, 1963 Accepted on July 2, 1964     

Anemia in Patients with Coinherited Thalassemia and Glucose-6-Phosphate Dehydrogenase Deficiency

Thalassemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are genetic disorders that cause hemolytic anemia. In areas with high frequencies of both hematological disorders, coinheritance of G-6-PD deficiency with thalassemia can be found. Whether G-6-PD deficiency, coinherited with thalassemia, enhances severe anemia is still unclear. Hematological parameters between thalassemia carriers with G-6-PD deficiency and those without G-6-PD deficiency were compared. The G-6-PD deficiency was diagnosed in 410 blood samples from thalassemia patients using a fluorescent spot test. The levels of hemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV) and Hb A₂/Hb E [β26(B8)Glu→Lys; HBB: c.79G>A] were measured using an automated blood counter and high performance liquid chromatography (HPLC), respectively. The G-6-PD deficiency was found in 37 samples (9.02%). Mean levels of Hb, PCV, MCV and Hb A₂/E were similar between the two groups. Thus, G-6-PD deficiency did not enhance red blood cell pathology or induce more anemic severity in thalassemia patients.     

Glucose-6-Phosphate Dehydrogenase Deficiency and Homozygous Sickle Cell Disease in Jamaica

S ummary . The relationship between D-glucose-6-phosphate: NADP oxido-reduc-tase (E.C.I.1.1.49; glucose-6-phosphate dehydrogenase; G6PD) deficiency and homozygous sickle cell (SS) disease was examined in 120 patients. The proportion of hemizygotes (22-6%) was slightly more than that observed, and the combined proportions of heterozygotes and homozygotes (28-3%) were slightly less than would be expected, in the general population, but the differences were not significant. However, the proportion of patients of abnormal G6PD status in the 10-19 years age group was 41-7%, significantly more than that found in the 20-29 years age group (0-02< P <0-05), or expected in the general population (P=0-05). Possible reasons for this are discussed. Difference in G6PD status did not affect the total haemoglobin concentration, reticulocyte count, unconjugated serum bilirubin or Hb F concentration, irreversibly sickled cell counts or plasma haemoglobin concentration, and there was no demonstrable correlation between clinical severity or leg ulceration and abnormal G6PD status.     

The Incidence of Glucose-6-Phosphate Dehydrogenase Deficiency and Thalassaemia in Malta

S ummary . A survey of G6PD deficiency in Malta including 1145 males and 369 females has shown that 2.7% of the males and 1.9% of the females have enzyme deficiency. More than 60% of the enzyme-deficient males but none of the females had decolorization times between 90 min and 24 hr. Using quantitative estimation of Hb A₂ as a measure of β-thalassaemia, an incidence of 3.4–3.6% was found. A raised Hb F was found in 2.3% of cases. The incidence of G6PD deficiency and thalassaemia does not seem to be correlated with intermarriage.     

Comparison of Quantitative and Qualitative Tests for Glucose-6-Phosphate Dehydrogenase Deficiency

A barrier to eliminating Plasmodium vivax malaria is inadequate treatment of infected patients. 8-Aminoquinoline–based drugs clear the parasite; however, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk for hemolysis from these drugs. Understanding the performance of G6PD deficiency tests is critical for patient safety. Two quantitative assays and two qualitative tests were evaluated. The comparison of quantitative assays gave a Pearson correlation coefficient of 0.7585 with significant difference in mean G6PD activity, highlighting the need to adhere to a single reference assay. Both qualitative tests had high sensitivity and negative predictive value at a cutoff G6PD value of 40% of normal activity if interpreted conservatively and performed under laboratory conditions. The performance of both tests dropped at a cutoff level of 45%. Cytochemical staining of specimens confirmed that heterozygous females with > 50% G6PD-deficient cells can seem normal by phenotypic tests.     

Glucose-6-Phosphate Dehydrogenase Activity in Platelets

The concentration of glucose-6-phosphate dehydrogenase (G-6-PD) wasfound to be 150-350 units per billion platelets in 52 normal individuals. In 21of 27 patients with thrombocytopenia the enzyme was found in normal concentrations.

Of the six cases showing thrombocytopenia with lowered enzyme concentration, five were examples of acute leukemia and one of disseminated lupuserythematosus.

In three individuals with "primaquine sensitive" erythrocytes the defect inthe platelet G-6-PD was also present.

The significance of the lowered enzyme activity in the six patients withthrombocytopenia is not known.

Submitted on October 24, 1960 Accepted on December 9, 1960     

Correlation of S Hemoglobin with Glucose-6-Phosphate Dehydrogenase Deficiency and Its Significance

Hemoglobin electrophoresis and methemoglobin reduction tests have beencarried out on 438 individuals with various hemoglobin patterns. The incidenceof the enzyme defect rises stepwise from AA pattern through AS, Sth and SCto SS being greatest in the latter. From the data presented it is not possible todecide what factors have produced this selection.

Submitted on June 15, 1964 Accepted on August 19, 1964     

Glucose-6-Phosphate Dehydrogenase Deficiency in a Native Danish Family A New Variant

Deficiency of red cell glucose-6-phosphate dehydrogenase was found in a native Danish family, in which 2 boys suffered from severe haemolytic anaemia. The mother and 3 sisters of the boys were heterozygotes for G-6-PD deficiency. The biochemical investigations indicate that this deficient G-6-PD is very similar to the Mediterranean variant; however, this variant gene may represent another example of G-6-PD ‘Helsinki’ or an unique variant with properties similar to G-6-PD B(—).     

Interaction between the Glucose-6-Phosphate Dehydrogenase Deficiency and Thalassaemia Genes at Phenotype Level

Summary. No significant differences were observed in the mean values of Hb A₂ levels and red cell indices between G6PD^- and G6PD+β thalassaemia carriers apart from the MCV, which was significantly higher in β thalassaemia G6PD^- subjects, but still in the thalassaemia carrier range. No difference was seen between G6PD+ and G6PD^-α thalassaemia carriers. G6PD+β thalassaemia carriers show a significant increase in G6PD levels expressed as activity per g of Hb and to lesser extent as activity per number of red cells x 10⁹; in G6PD+α thalassaemia carriers this increase is statistically significant only when the enzyme levels are expressed as activity per g of Hb. G6PD^-β thalassaemia carriers had enzyme levels higher than non-thalassaemic G6PD^- subjects only when the activity is expressed per g of Hb. G6PD activity was found to be increased in G6PD+ and G6PD^- Hb H disease patients.     

Erythrocyte Superoxide Dismutase,Catalase and Glutathione Peroxidase in Glucose-6-Phosphate Dehydrogenase Deficiency

Glucose-6-phosphate dehydrogenase (G-6-PD) deficient erythrocytes are particularly sensitive to oxidant stress. In order to evaluate if these cells are protected against oxidant damage, we assayed the antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in erythrocytes of G-6-PD deficient (hemizygous and heterozygous) subjects. Normal levels of antioxidant enzymes were found in all subjects examined both with positive and negative histories of haemolytic crisis after fava bean or drug ingestion. In contrast, high levels of catalase and GSH-Px were found in a small group of G-6-PD deficient subjects (hemizygous and heterozygous) with β-thalassaemia trait, probably by reason of the chronically enhanced oxidant stress which is present in β-thalassaemia.     

A Tetrazolium-Linked Cytochemical Method for Estimation of Glucose-6-Phosphate Dehydrogenase Activity in Individual Erythrocytes: Applications in the Study of Heterozygotes for Glucose-6-Phosphate Dehydrogenase Deficiency

A new method is described for the graded estimation of G6PD activity inindividual erythrocytes. The method appears to offer some technical advantages over other methods. It requires reagents that are neither hazardous norunstable and such equipment as might be found in the usual hematology laboratory. It appears to be more sensitive than conventional methods for identification of women heterozygous for G6PD deficiency and further substantiatesthe existence of erythrocyte mosaicism in such individuals.

Submitted on July 12, 1967 Accepted on October 18, 1967     

Evaluation of a Rapid Qualitative Enzyme Chromatographic Test for Glucose-6-Phosphate Dehydrogenase Deficiency

Rapid determination of glucose-6-phosphate dehydrogenase (G6PD) status is desirable when it is necessary to use a drug contraindicated in G6PD-deficient persons, such as use of primaquine for malaria prevention or treatment. The purpose of this study was to compare a new, rapid, qualitative enzyme chromatographic test for deficiency of G6PD to a standard reference method. Samples from 196 G6PD-normal persons and 50 G6PD-deficient persons were evaluated. The sensitivity of the experimental rapid test was 0.98 and the specificity was 0.98 using specimens preserved in heparin, and 0.98 and 0.97, respectively, for specimens preserved in EDTA. Positive and negative predictive values were 0.72 and 1.00, respectively, for the test for heparinized specimens and 0.65 and 1.00, respectively, for the EDTA-preserved samples. This rapid test for G6PD deficiency is a sensitive method for screening of G6PD deficiency that requires minimal training and equipment and enables rapid identification of G6PD-deficient persons.     

The Elderly with Glucose-6-Phosphate Dehydrogenase Deficiency are More Susceptible to Cardiovascular Disease

Aim: Recent studies suggest that glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetically inherited condition causing hemolytic anemia, may be a risk factor for cardiovascular disease (CVD). We aimed to perform a retrospective case–control study in Sardinia taking advantage from clinical records of patients undergoing upper digestive endoscopy and screened for H. pylori infection. Methods: A total of 9,604 patients with a known G6PD status and a complete clinical history, encompassing CVD, and leading CVD risk factors, including H. pylori infection, undergoing upper endoscopy between 2002 and 2017 were enrolled in this study. Results: Multivariate logistic regression analysis confirmed an increased CVD risk in subjects with G6PD deficiency [odd ratio (OR), 3.24; 95% confidence interval (CI) 2.44–4.30] after adjusting for potential confounders and effect modifiers, including H. pylori infection. Cardiovascular risk was similar in subjects with and without G6PD deficiency before age 60 (OR, 1.26; 95% CI 0.78–2.04, P =0.562), whereas it increased after age 60 in the former group (OR, 3.05; 95% CI 2.22–4.19, P ＜0.0001) especially in males (OR 3.67; 95% CI 2.19–6.14) compared with females (OR, 2.96; 95% CI 1.89–4.64) by sex-specific logistic regression analysis. Conclusion: The risk of CVD was greater in G6PD-deficient subjects after age 60, both in males and females, than those with normal enzyme activity, after adjusting for conventional CVD risk factors and H. pylori infection. The reduction of important protective mechanisms against oxidative stress in the elderly might explain the study findings.