Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency.

People with the variants of glucose-6-phosphate dehydrogenase (GPD) deficiency common in the southern Chinese (Canton, B(-)Chinese, and Hong Kong-Pokfulam) have a moderate shortening of red-cell survival but no anaemia when they are in the steady state. With a cross-transfusion technique, primaquine, nitrofurantoin, and large doses of aspirin were found to aggravate the haemolysis while sulphamethoxazole did so only in some people. Individual differences in drug metabolism may be the reason for this. Many commonly used drugs reported to accentuate haemolysis in GPD deficiency did not shorten red-cell survival.     

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.     

The molecular basis of glucose-6-phosphate dehydrogenase deficiency.

With more than 300 different variants reported, the human enzyme glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is one of the most polymorphic proteins known. An estimated 400 million people throughout the world are deficient in G6PD; numerous lines of evidence indicate that this is because female heterozygotes have a selective advantage in malaria infections. The cloning of the G6PD gene has made it possible to clarify the molecular basis underlying this enzyme deficiency and polymorphism.     

X-linked glucose-6-phosphate dehydrogenase deficiency inMus musculus

A mouse with X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency has been recovered in offspring of 1-ethyl-1-nitrosourea-treated male mice. The activity alteration was detected in blood but can also be observed in other tissue extracts. Hemizygous, heterozygous, and homozygous mutants have, respectively, about 15, 60, and 15% G6PD remaining activity in the blood as compared to the wild type. Erythrocyte indices did not show differences between mutants and wild types. The mutation does not affect the electrophoretic migration, the isoelectric point, or the thermal stability. Kinetic properties, such as theK _m for glucose-6-phosphate or for NADP and the relative utilization of substrate analogues, showed no differences between wild types and mutants with the exception of the relative utilization of deamino-NADP which was significantly lower in mutants. This is presently the only animal model for X-linked G6PD deficiency in humans.This research was supported in part by Contract BI6-156-D from the Commission of the European Communities.     

Heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Algeria

Summary Glucose-6-phosphate dehydrogenase (G6PD) deficiency was found in 3.2% of the male population living in the urban area of Algiers. The deficient subjects originated from multiple geographic regions of Northern Algeria, with prevalence of individuals of Berber-Kabyle origin. Red blood cell G6PD was partially purified and characterized in deficient males from 17 families, and six different variants were found. Among them, only one, the Gd(-) Kabyle variant, had been previously described. It was detected in nine families. The other five variants were new: Gd(-) Laghouat (four cases), Gd(-) Blida (one case), Gd(-) Thenia (one case), Gd(-) Titteri (one case), and Gd(-) Alger (two brothers), Strikingly, the common Mediterranean variant was not found. G6PD deficiency is heterogeneous in northern Algeria where autochtonous variants seem to prevail. The Kabyle variant may be common in this country.     

Red cell glucose-6-phosphate dehydrogenase deficiency among Andhras

Sixty-eight Andhra males and 45 Andhra females from Visakhapatnam town of Andhra Pradesh, India have been investigated for G-6-PD deficiency. The GdB- gene has a frequency of 4.41% among males. No G-6-PH deficient females were detected. The present data have been compared with the available tribal and non-tribal data from Andhra Pradesh. It is observed that the present sample, though non-tribal in nature, presents a relatively considerable frequency of the GdB- gene.     

Detection of female heterozygous glucose-6-phosphate dehydrogenase deficiency]

Diagnostics of heterozygotes are required for population studies, for the detection and consultation of persons with G-6-PD deficiency prone to hemolysis. The diagnostics of heterozygous females with the corresponding trait are problematic in families without hemizygous patients. 1. The determination of the activity is only applicable to the differentiation between heterozygotes and homozygotes if the activities are below the reference range. Heterozygous G-6-PD deficiency with normal activity cannot be identified by this method. 2. Existence of G-6-PD defects is demonstrated by mosaicism even in case of normactivity (T?nztest). 3. Incubation with and without NADP of stroma-free hemolysates involving heat labile enzyme mutants results in a marked decrease of activity within 20 min at 46 degrees C. 4. Electrophoresis on Cellogel demonstrates changes of charge in the mutated enzyme. 5. Family examination verifies suspicion of the heterozygous trait. A combination of parameters is recommended to obtain an improvement in the detection of persons with the heterozygous trait.     

Frequency of glucose-6-phosphate dehydrogenase phenotypes and deficiency in Al-Baha

This investigation was conducted on 847 males and females in Al-Baha, the mountainous western province of Saudi Arabia, to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) phenotypes and G6PD deficiency. Among the G6PD phenotypes, G6PD B+, G6PD A+, G6PD A-, G6PD Mediterranean and G6PD Mediterranean-like were identified with a gene frequency in the male population of 0.7769, 0.0119, 0.0020, 0.1255 and 0.0817, respectively, and in the females with a frequency of 0.722, 0.003, 0.003, 0.1128 and 0.1311, respectively. Heterozygous females with the phenotypes of G6PD B+/A+ and B+/A- were identified with a frequency of 0.0183 and 0.0090, respectively. The frequency of severe G6PD deficiency in this population was 0.1275 and 0.1158 in males and females, respectively.