Cortisol levels in glucose-6-phosphate dehydrogenase deficiency.

The aim of the present study was to investigate cortisol levels under basal conditions and in response to ACTH stimulation in male patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. The study included 14 male controls and 12 patients with G-6-PD deficiency matched for age and race. Fasting blood samples were taken from all the subjects at rest, and 30, 60 and 120 min after the infusion of 0.25 mg of corticotropin for cortisol determination. The mean cortisol levels observed in the first hour after ACTH stimulation in the G-6-PD-deficient patients were significantly (p = 0.03) lower than in the control group. No significant differences were observed between patients and controls at rest, and in the second hour after stimulation. These data suggest that, in the adrenals, G-6-PD plays a role in the initial phase of cortisol production. However, 1 h after ACTH stimulation, G-6-PD probably is no longer rate limiting in the production of cortisol.     

Glucose-6-phosphate dehydrogenase deficiency and sickle cell disease in Brazil.

The frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency was determined in 54 male patients with sickle cell diseases: 31 sickle cell anemia (SS), 14 sickle cell hemoglobinopathy (SC) and 9 HbS/beta-thalassemia (S/B-thal) by a combination of quantitative assay, fluorescent spot test and electrophoresis. Of the 54 patients tested, 7 were found to be G-6-PD deficient (G-6-PD-) (3 SS, 3 SC and 1 S/B-thal) and 47 G-6-PD normal (G-6-PD+) (6 G-6-PD A and 41 G-6-PD B). All the deficient patients were G-6-PD A-. The frequency of G-6-PD deficiency did not differ significantly from that observed in the general population. Compared to patients who were not G-6-PD-, there were no significant differences in the hemoglobin concentration and reticulocyte count in patients with sickle cell diseases who were G-6-PD-.     

Leucocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity in G-6-PD deficient Chinese

The activity of glucose-6-phosphate dehydrogenase (G-6-PD) in leucocytes was studied for erythrocyte G-6-PD deficiency using 49 hemizygous males, 16 heterozygous females, and 19 normal controls. The mean G-6-PD activity in leucocytes of the affected neonates (9.2 +/- 5.4 units) and the children (11.2 +/- 5.3 units) were significantly lower than those of normal newborns (22.9 +/- 5.1 units, P less than 0.01). Seventy percent of the effected newborns and 58% of the children with G-6-PD deficiency had the leucocyte enzyme activity of less than 13 IU/10(9)WBC. The leucocyte enzyme activity (14.6 +/- 8.6 units) of 16 heterozygous G-6-PD deficient mothers was also lower than that of normal controls (23.1 +/- 7.0 units). The present study thus concludes that, in G-6-PD deficient Chinese, the enzyme defect is demonstrable not only in erythrocytes but also in leucocytes.     

Glucose-6-phosphate dehydrogenase Boston

Summary A hitherto undescribed variant of erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity, G-6-PD Boston, is described in a 24-year-old Caucasian male of Polish-Jewish ancestry. A marked decrease in red cell G-6-PD activity was associated, in this individual, with a compensated hemolytic process. The electrophoretic mobility of the partially purified enzyme on cellulose acetate at pH 9.1 and on starch gel was indistinguishable from normal but the apparent K_m for both G-6-PD (18–21 M) and NADP (1.7–2.2) was significantly decreased. Preliminary evidence supports the concept that G-6-PD Boston may not be extremely rare among this particular population group.     

Studies of enzymes connected with erythrocyte glutathione metabolism in a rural tropical population

Summary The activities of the erythrocyte enzymes hexokinase (HK), glucose-6-phosphate dehydrogenase (G-6-PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione peroxidase (GSH-PO) were determined in a group of 12 Europeans and in a group of 103 male Thai subjects in northern Thailand. In the Thai group there were 16 subjects with G-6-PD deficiency and 28 subjects with abnormally low levels of GR activity. A comparison of the enzyme activities in the different subgroups indicated that HK and 6-PGD are not influenced by G-6-PD deficiency whereas GR and GSH-PO activities are significantly higher in G-6-PD deficient subjects. In the group with low GR activity G-6-PD and GSH-PO showed a tendency to an elevation of activity when compared with the normal control group. Significant positive correlations exist between G-6-PD and 6-PGD in the normal group and between GR and GSH-PO in the G-6-PD deficient group. A negative correlation between GR and GSH-PO was present in the group with low GR activities. A study of the families of subjects with low activity of GR did not yield evidence for the existence of a deficiency polymorphism.

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Zusammenfassung Bei 12 Europäern und einer Gruppe von 103 männlichen thailändischen Versuchspersonen wurden die Aktivitäten der Erythrocytenenzyme Hexokinase (HK), Glucose-6-Phosphat-Dehydrogenase (G-6-PD), 6-Phosphogluconat-Dehydrogenase (6-PGD), Glutathion-Reduktase (GR) und Glutathion-Peroxidase (GSH-PO) bestimmt. In der Thai-Gruppe waren 16 Personen mit G-6-PD-Mangel und 28 Personen mit abnormal niedrigen Aktivitäten der GR. Ein Vergleich der Enzymaktivitäten in verschiedenen Untergruppen zeigte, daß HK und 6-PGD durch G-6-PD-Mangel nicht beeinflußt werden. Im Gegensatz hierzu sind die Aktivitäten der GR und der GSH-PO bei G-6-PD-Mangel signifikant erhöht. In der Gruppe mit erniedrigter GR-Aktivität bestand eine Tendenz zu erhöhten Werten für G-6-PD und GSH-PO. Die Korrelationen zwischen G-6-PD und 6-PGD in der Gruppe mit normaler G-6-PD und die zwischen GR und GSH-PO in der Gruppe mit G-6-PD-Mangel waren signifikant. In der Gruppe mit erniedrigter GR-Aktivität fand sich eine negative Korrelation zwischen GR und GSH-PO. Die Untersuchungen in Familien von Personen mit niedriger GR-Aktivität ergaben keinen sicheren Hinweis auf das Vorliegen eines GR-Mangel-Polymorphismus in der untersuchten Bevölkerung.

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Established and supported by Stiftung Volkswagenwerk, Hannover.     

Insulin secretion in patients deficient in glucose-6-phosphate dehydrogenase

Intravenous (IVGTT) and oral glucose tolerance tests (OGTT) were carried out in 12 men with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and in 11 normal men. The race, the mean age and body mass index were similar in the G-6-PD deficient and in the normal men. No significant differences were demonstrated between mean plasma glucose levels in the G-6-PD deficient subjects and those in the normal men during IVGTT and OGTT. In contrast the insulin levels were significantly lower for the G-6-PD deficient subjects as compared to the controls at 30 minutes (P less than 0.04) in the OGTT and at 1 min (P less than 0.001), 3 min (P less than 0.001), 5 min (P less than 0.001) and 10 minutes (P less than 0.002) in the IVGTT. All indexes of first phase insulin release were also significantly (P less than 0.001) lower in G-6-PD deficient men. These results emphasize the metabolic importance of G-6-PD in the process of glucose induced insulin release.     

Characteristics of a new abnormal variant of G-6-PD in human red cells.

Kinetic and electrophoretic properties were studied in 230--300 fold purified preparations of glucose-6-phosphate dehydrogenase (G-6-PD) from red cells of donors and patients with hemolytic anemia induced by G-6-PD deficiency. In abnormal variant of G-6-PD isolated from red cells of a patient with hemolytic anemia which had not before been described in the literature was found. The abnormal variant differs from the normal enzyme by a decreased Michaelis constant for G-6-P and NADP, by increased utilization of substrate-analogues (2-deoxy-G-6-P and deamino NADP in particular), by low heat stability, the character of pH dependence, and by the appearance of one band of G-6-PD activity during electrophoresis in polyacrylamide gel. The isolated abnormal variant of G-6-PD has been called "Kremenchug" according to the origin of the patient.     

Glucose-6-?hosphate dehydrogenase deficiency,haptoglobin and hemoglobin variants in dogs

Blood samples from 31 male and 34 female, adult, healthy dogs of different breeds were studied for erythrocytic G-6-PD activity. The hemolysates were also studied electrophoretically for G-6-PD, 6-PGD, and hemoglobin variants. Most of the plasma samples revealed a human Hp 1–1 type of band while three samples had an additional fast-moving band that disappeared on addition of an excess of hemoglobin and two samples were ahaptoglobinemic. G-6-PD deficiency was detected in eight samples, and it was more frequent in males than in females. The implications of G-6-PD deficiency with no difference in the electrophoretic pattern and of ahaptoglobinemia are discussed with respect to different genetic and clinical possibilities.     

Glucose-6-phosphate dehydrogenase in the population of northern Thailand: Evidence for two common electrophoretic variants with deficient enzyme activity

Summary Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, identified by a dye decolorization test, was found in 101 (12.5 percent) of 811 male subjects from northern Tailand. Blood samples from 169 subjects with normal G-6-PD activity and from all 101 subjects with G-6-PD deficiency were examined by electrophoresis on cellulose acetate gel with the following results: In all samples with normal G-6-PD activity the enzyme had the electrophoretic mobility of type B G-6-PD. 73 of the 101 G-6-PD deficient samples had the same mobility and are therefore probably identical with the common Mediterranean variant B-. 16 of the 101 deficient samples contained an electrophoretically fast G-6-PD, and 1 sample a slow variant. In 11 deficient samples the enzyme could not be made visible. Kinetic studies on crude hemolysates suggest that the fast variant has a higher mean activity and heat stability in comparison to the B- variant.Established and supported by Stiftung Volkswagenwerk, Hannover.     

Red Cell Glucose-6-Phosphate Dehydrogenase Deficiency—A Newly Recognized Cause of Neonatal Jaundice and Kernicterus in Canada

Seven male newborns of Chinese, Greek and Italian origin presented with severe hemolytic jaundice due to red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. In five, the hemolysis was precipitated by inhalation of mothball vapours in the home. Kernicterus was evident upon admission in six infants and was fatal in four of these.G-6-PD deficiency should be suspected as a cause of jaundice in all full-term male infants of these ethnic groups. The diagnosis can be confirmed in any hospital by the methemoglobin reduction test. In areas similar to Toronto, Canada, where these high-risk ethnic groups prevail, the following measures are recommended: (1) detection of G-6-PD deficient newborns by screening cord bloods of all infants of these ethnic groups; (2) protection of affected infants from potentially hemolytic agents such as naphthalene, certain vitamin K preparations, and sulfonamides; and (3) observation of serum bilirubin levels to assess the need for exchange transfusion for hyperbilirubinemia.     

Haemolysis complicating viral hepatitis in patients with glucose-6-phosphate dehydrogenase deficiency.

Out of 20 patients with viral hepatitis whose glucose-6-phosphate dehydrogenase (G-6-PD) levels were normal, 14 had clinical evidence of a mild to moderate degree of haemolysis but in all the patients studied the half life of chromium-51-labelled red cells was shortened. Out of 18 viral hepatitis patients deficient in G-6-PD 17 had clinical evidence of haemolysis, and in eight this was more severe than in the group with normal G-6-PD values. Massive intravascular haemolysis occurred in four, three of whom died. The massive haemolysis was attributed to the presence of additional drug-induced oxidative stress to the G-6-PD-deficient red cells.     

Isolation of mammalian cell mutants deficient in glucose 6-phosphate dehydrogenase by means of a replica-plating technique

Summary A replica-plating technique is described which was used for the isolation of G-6-PD-deficient mutants in cultures of mutagen-treated Chinese hamster cells. Mutants were recognized by their failure to stain in a histochemical G-6-PD-specific staining reaction. Four mutants were isolated and characterized by growth properties, stability of their variant phenotypes, and reduced G-6-PD activity. One of these mutants on electrophoresis exhibited a variant G-6-PD and thus is very likely the result of a mutation in the structural gene for G-6-PD.     

A new glucose-6-phosphate dehydrogenase variant (G-6-PD Kalyan) found in a Koli family

Summary A new Indian variant of erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) has been detected in a Koli male subject during population genetic studies. The enzyme variant is characterized by mild enzyme deficiency, slow electrophoretic mobility, low K_m for G-6-P, increased utilization of substrate analogues, heat instability and a normal pH optimum curve. From these results this was considered to be a new variant and was designated G-6-PD Kalyan. The family history and routine hematological studies did not reveal any evidence that the G-6-PD Kalyan is associated with any hematological abnormalities or clinical symptoms.     

Human platelet glucose-6-phosphate dehydrogenase. Total purification, kinetic studies and relationship with enzyme from other blood cells.

Human platelet G-6-PD has been highly purified, to homogeneity, and its kinetic, electrophoretic and immunological characteristics have been studied. Platelet G-6-PD differs from erythrocyte or leukocyte enzymes by an increased Michaelis constant for G-6-P and a slow activity at the acid pHs. By electrofocusing only a main active band (band a) of platelet G-6-PD was found. The incubation at 37 degrees C in the presence of NADP+ and dithiothreitol normalize Km-G-6-P of platelet G-6-PD; the incubation with boiled and ultrafiltered leukemic granulocyte extracts led to an anodisation of G-6-PD active forms, a decrease of the molecular specific activity and a further increase of Km-G-6-P; these last modifications are the same as those undergone by G-6-PD incubated in crude extracts of normal or leukemic granulocytes.     

Frequency of glucose-6-phosphate dehydrogenase deficiency in sickle-cell disease. A study in Saudi Arabia

The frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 50 Hb S homozygotes (SS) and 98 Hb S heterozygotes (AS) was determined and compared with the frequency obtained in individuals with normal haemoglobin (AA). The observed number of SS patients with G-6-PD deficiency was significantly greater than the expected value (p less than 0.05). The frequency of G-6-PD deficiency in AA, AS and SS was found to be 0.172, 0.214 and 0.420, respectively. A statistically significant increase of G-6-PD deficiency was apparent in the Saudi sicklers. The possibility that G-6-PD deficiency and Hb S gene interact, influencing the survival of the carriers of these genetic abnormalities, is discussed.     

Red cell glucose-6-phosphate dehydrogenase deficiency and haemoglobin variants among ten endogamous groups of Maharashtra and West Bengal

Summary Over 900 individuals from ten endogamous groups in the Indian states of Maharashtra and West Bengal were studied for G-6-PD deficiency and haemoglobin variants. The incidence of G-6-PD varied from nil to 17.3%, while that of Hb-S varied from nil to 22.3%. In general, the tribal populations of Maharashtra are characterized by the presence of a high incidence of both Hb-S and G-6-PD deficiency. The caste Hindus showed an absence of Hb-S and rather low G-6-PD deficiency. Immigrant Parsis possessed the highest incidence of G-6-PD deficiency (17.3%).     

Frequency of glucose-6-phosphate dehydrogenase, pyruvate kinase and hexokinase deficiency in the Saudi population

The frequencies of glucose-6-phosphate dehydrogenase (G-6-PD), pyruvate kinase (PK) and hexokinase (HK) deficiency were determined in different regions of Saudi Arabia. G-6-PD deficiency was found to range from 0.045 to 0.220 for the male and 0.020 to 0.125 for the female population. The highest frequencies were found to exist in the regions which are endemic to malarial parasite and have high frequencies of sickle cell and thalassaemia genes. Partial deficiencies of PK and HK were encountered in each region, however, no case of complete deficiency of these enzymes was identified. Further investigations are in progress to determine the clinical manifestations of enzyme deficiencies in the Saudi population.     

Aspects of sickle cell gene in Saudi Arabia—interaction with glucose-6-phosphate dehydrogenase deficiency

Summary Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell haemoglobin (Hb S) are red cell genetic abnormalities that occur at a high frequency in several areas of the world including several areas of Saudi Arabia. Genetic and clinical interactions between these two disorders are reported to occur in some populations.In the present investigations, samples from affected individuals were studied for the prevalence of G-6-PD deficiency and Hb S genes. The results of haematological parameters and common clinical findings in the Hb S homozygotes with and without G-6-PD deficiency are presented and the possibility that the two conditions interact beneficially is discussed.     

G-6-PD Poznań, variant with severe enzyme deficiency.

A new variant of G-6-PD with severe enzyme dificiency without chronic hemolysis is characterized. The biochemical properties of the variant closely resemble those of the G-6-PD Ramat-Gan described in a case of chronic non-spherocytic hemolytic anemia. As the family data on linking of chronic hemolysis with Ramat-Gan variant are lacking, the differentiation of the variants on the basis of clinical manifestations is not well-founded.     

Characterization of glucose-6-phosphate dehydrogenase in Thailand

Summary Characterization of partially purified eryrhrocyte G-6-PD from 50 enzymedeficient males in 45 unrelated Thai families revealed 6 enzyme variants. Thirty-five subjects in 31 families had G-6-PD variant with normal electrophoretic mobility, slightly low Km G-6-P, normal substrate-analog utilization, normal pH-optimum curve, and slightly increased heat stability. This enzyme variant is called G-6-PD Mahidol.Six subjects had enzyme with fast electrophoretic mobility (106–108% of normal), low Km G-6-P, slightly increased substrate-analog utilization, biphasic pH-optimum curve, and slightly low to normal heat stability. This variant was identical to G-6-PD Canton.Five subjects had G-6-PD with fast electrophoretic mobility (103–106% of normal), low Km G-6-P, very high substrate-analog utilization except for DPN which it did not use as cofactor, markedly biphasic pH-optimum curve and very low heat stability. This variant is called G-6-PD Union (Thai).Two brothers had G-6-PD with normal electrophoretic mobility, low Km G-6-P, slightly increased substrate-analog utilization, biphasic pH-optimum curve and low heat stability. This variant is designated G-6-PD Siriraj.G-6-PD from one patient had slightly fast electrophoretic mobility, increased substrateanalog utilization, especially of DPN, and very low thermal stability. It is called G-6-PD Kan.One subject had G-6-PD with normal electrophoretic mobility, Km G-6-P, pH-optimum curve and heat stability, and increased substrate-analog utilization. This G-6-PD variant is named G-6-PD Anant.G-6-PD Mahidol is far more common than any other known variants in Thailand.

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Zusammenfassung Eine Charakterisierung von teilweise gereinigtem Erythrocyten-G-6-PD von 50 Männern mit Enzym-Defekt aus 45 nicht miteinander verwandten Thai-Familien ergab 6 Enzym-Varianten. 35 Personen in 31 Familien hatten eine G-6-PD-Variante mit normaler elektrophoretischer Wanderungsgeschwindigkeit, einen leicht verminderten G-6-P-Km-Wert, einer normalen Substratanalog-Verwertung, einer normalen pH-Optimum-Kurve und einer leicht erhöhten Hitze-Stabilität. Diese Enzym-Variante wurde G-6-PD Mahidol genannt.Sechs Personen hatten ein Enzym mit rascher elektrophoretischer Wanderung (106–108% der Norm), niedrigem Km für G-6-P, leicht erhöhter Substrat-Verwertung, einer biphasischen pH-Optimum-Kurve und normaler bis leicht erniedrigter Hitzestabilität. Diese Variante ist identisch mit G-6-PD Canton.Fünt Personen hatten G-6-PD mit rascher elektrophoretischer Wanderung (103–106%), niedrigem Km G-6-P, sehr hoher Substratanalog-Verwertung—mit Ausnahme von DPN, das nicht als Cofactor wirkte—, einer stark biphasischen pH-Optimum-Kurve und sehr geringer Hitze-Stabilität. Diese Variante wurde als G-6-PD Union (Thai) bezeichnet.Zwei Brüder hatten ein G-6-PD mit normaler elektrophoretischer Wanderung, niedrigem Km G-6-P, leicht erhöhter Substratanalog-Verwertung, einer biphasischen pH-Optimum-Kurve und geringer Hitze-Stabilität. Diese Variante erhielt den Namen G-6-PD Siriraj.G-6-PD eines Patienten hatte eine leicht erhöhte elektrophoretische Wanderungsgeschwindigkeit, eine erhöhte Substratanalog-Verwertung, besonders für DPN, und eine sehr geringe Hitze-Stabilität (G-6-PD Kan).Eine Person zeigte ein G-6-PD mit normaler elektrophoretischer Wanderungsgeschwindigkeit, Km G-6-P pH-Optimum-Kurve und Hitze-Stabilität. Nur die Substratanalog-Verwertung war erhöht. Diese Variante wurde G-6-PD Anant gennant.G-6-PD Mahidol ist die bei weitem häufigste Variante in Thailand.

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This investigation received financial support from the World Health Organization.