Molecular genetics of glucose-6-phosphate dehydrogenase deficiency in Mexico

PURPOSE: To report the results of a prospective study of the incidence of peripheral visual field loss after macular hole surgery. METHODS: Prospectively, 30 eyes of 30 consecutive patients with full-thickness macular holes operated on between December 1995 and April 1996 had preoperative and postoperative Goldmann visual field tests. The surgical procedure consisted of three-port pars plana vitrectomy, posterior hyaloid removal, nonexpansile fluid-hexafluoroethane (C2F6) exchange, and, in 19 of 30 patients, autologous platelet injection, followed by face-down positioning. RESULTS: Twenty-nine of these 30 cases were considered to be anatomic successes. Comparison of preoperative and postoperative visual fields disclosed that four patients (13%) had a peripheral scotoma, including one patient with stage 4 macular hole. Three other patients (10%) had a postoperative relative arcuate defect. Mean postoperative intraocular pressure was higher in the latter group. None of the patients complained of peripheral scotoma. CONCLUSIONS: Overall, seven of 30 patients (23%) had a postoperative visual field defect. Two categories of scotomas were observed: peripheral and relative arcuate. The cause of peripheral visual field loss is unclear. Increased intraocular pressure may be the cause of relative arcuate scotomas.     

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.     

HLA antigens and erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in Sardinia

Wind enhances the carcinogenic effect of chronic Iltraviolet radiation (UVL). This was demonstrated in hairless mice that were irradiated for 42 weeks with mercury are lamps. One group of animals was exposed to continuous wind flow of 2.7 m/s except for the daily I-2 min time interval when they were removed from the wind tunnel and irradiated. Another group of animals received identical irradiation but were protected from wind. The first tumour appeared in the UVL and wind group after 105 days of irradiation, and at 164 days of irradiation all surviving mice in the group had developed tumours. The group of mice receiving identical irradiation but protected from wind had their first tumour appear at 154 days of irradiation, and by 164 days of irradiation only 40% of the mice had developed tumours.     

Mortality in a cohort of men expressing the glucose-6-phosphate dehydrogenase deficiency

The objective of this study was to test the hypothesis of a lower mortality from cancer and cardiovascular diseases among men expressing glucose-6-phosphate dehydrogenase (G6PD) deficiency. We designed a mortality study based on death certificates from January 1, 1982 through December 31, 1992 in a cohort of G6PD-deficient men. Cohort members were 1,756 men, identified as expressing the G6PD-deficient phenotype during a 1981 population screening of the G6PD polymorphism. The setting was the island of Sardinia, Italy. Outcome measures were cause-specific standardized mortality ratios (SMRs), which were computed as 100 times the observed/expected ratio, with the general Sardinian male population as the reference. Deaths from all causes were significantly less than expected due to decreased SMRs for ischemic heart disease (SMR, 28; 95% confidence interval [CI], 10 to 62), cerebrovascular disease (SMR, 22; 95% CI, 6 to 55), and liver cirrhosis (SMR, 12; 95% CI, 0 to 66), which explained 95.6% of the deficit in total mortality. All cancer mortality was close to the expectation, with a significant increase in the SMR for non-Hodgkin's lymphoma (SMR, 545; 95% CI, 147 to 1,395). A decrease in mortality from cardiovascular diseases was one of the study hypotheses, based on an earlier human report and experimental evidence. However, selection bias is also a likely explanation. Further analytic studies are warranted to confirm whether subjects expressing the G6PD-deficient phenotype are protected against ischemic heart disease and cerebrovascular disease. This cohort study is consistent with more recent case-control studies in rejecting the hypothesis of a decreased cancer risk among G6PD-deficient subjects. The observed increase in mortality from non-Hodgkin's lymphoma and decrease in mortality from liver cirrhosis were not previously reported.     

Genetic analysis of the glucose-6-phosphate dehydrogenase deficiency in a southern Croatia

PURPOSE: To evaluate objectively the effects of a microbubble contrast agent on the color Doppler ultrasound (US) examination of breast lesions. MATERIALS AND METHODS: Forty-seven patients aged 23-71 years underwent color Doppler US before and after intravenous injection of a microbubble contrast agent. A 3-minute computer-assisted assessment of the color pixel density (CPD) was used to evaluate objectively the increase in the number of color Doppler US signals, the transit time of the microbubble bolus, and the potential additional differential diagnostic information. RESULTS: Peak CPD at contrast agent-enhanced color Doppler US was 14.3% +/- 8.1 (mean +/- 1 standard deviation) for carcinomas and 9.3% +/- 4.9 for benign lesions (P = .04). The time to peak enhancement was shorter in carcinomas (38 seconds +/- 20) than in benign tumors (71 seconds +/- 48, P = .02). Final CPD was close or equal to baseline values. With the median of 13% for peak CPD as a threshold, the sensitivity for this parameter was 55%, the specificity was 79%, and the accuracy was 62% (P = .04). For a median time to peak of 50 seconds, the sensitivity was 84%, the specificity was 57%, and the accuracy was 76%. CONCLUSION: After microbubble contrast agent injection, carcinomas and benign lesions behave differently in degree, onset, and duration of Doppler US enhancement. High interindividual variability and temporal variations in the Doppler US signal still limit the value of these criteria for prospective diagnosis.     

Severe neonatal hyperbilirubinemia. A potential complication of glucose-6-phosphate dehydrogenase deficiency

G-6-PD deficiency is frequently associated with neonatal hyperbilirubinemia, which may be severe enough to cause kernicterus and death. Because of its association with acute trigger-induced hemolytic crises, G-6-PD deficiency-associated neonatal hyperbilirubinemia has been labelled as hemolytic in origin. In this article, the authors summarize recent evidence demonstrating that hemolysis cannot in and of itself be responsible for jaundice and that decreased bilirubin elimination plays a major role in its pathogenesis.     

An autosomal glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) polymorphism in human saliva

Glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) from human saliva has been demonstrated by the zymogram technique. Three phenotypes were found. Family and population studies suggested that these phenotypes are the products of an autosomal locus with two alleles Sgd-1 and Sgd-2.     

Oxidant damage to erythrocyte membrane in glucose-6-phosphate dehydrogenase deficiency: correlation with in vivo reduced glutathione concentration and membrane protein oxidation

Chronic nonspherocytic hemolytic anemia has been observed in a recently described glucose-6-phosphate dehydrogenase (G6PD) variant, G6PDWayne. The mechanical properties of these erythrocytes and other G6PD variants were examined. The deformability of G6PD-deficient erythrocytes was normal, as determined by osmotic scan ektacytometry, and was not significantly affected by hemolytic crisis. In the common varieties of G6PD deficiency, the mechanical stability of the red blood cell (RBC) membrane was greater than normal, but G6PDWayne membranes were abnormally susceptible to shear-induced fragmentation. There was no evidence for a concurrent genetic defect in spectrin, because self-association constants and tryptic digests were normal. The fragility of G6PDWayne membranes appeared to be a consequence of oxidative damage to membrane thiol groups associated with a low glutathione (GSH) level in these RBCs. Associations among GSH level, thiol oxidation, and membrane instability were also found when a larger group of G6PD-deficient RBCs were examined. In normal erythrocytes, 1-chloro-2,4-dinitrobenzene was used to reduce GSH levels by 50%. Membrane thiol oxidation and membrane fragility both increased when these cells were kept at 4 degrees C for 3 to 5 days. Our findings suggest that chronic depletion of GSH leads to the destabilization of membrane skeleton through oxidation of membrane protein thiols.     

Analysis of common mutations and associated haplotypes in Chinese patients with glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a rare disease in North China. In the present investigation, DNA samples from 17 patients with G6PD deficiency from Tianjin area in North China were studied for the two G6PD common mutations (R459L and R463H) and two single nucleotide polymorphisms (1311C/T and 1365-13T/C) using a dideoxy fingerprinting method. Five patients were positive for mutation R459L, and six patients were positive for mutation R463H. Further haplotype analyses using three flanking dinucleotide repeat polymorphism loci, DXS1123, DXS1113, and F8C(IVS13), were performed on 14 patient families and 16 control Chinese females. The results indicated that the two common mutations were from different haplotypes. Also, the data suggested a possible allelic association between the two G6PD common mutations and the F8C(IVS13) locus and a different allelic distribution for loci DXS1113 and F8C(IVS13) between Chinese and Caucasian populations.     

Siamese twins in the United Arab Emirates

In the years 1985-1992, ten pairs of conjoined twins were born in the United Arab Emirates (UAE): one dicephalus, two teratopagi, and seven thoracoomphalopagi, one of which was still-born and three who were cared for in other hospitals. The first pair of thoraco-omphalopagus twins died of acute lymphoblastic leukaemia 6 months after successful separation. The management of the third set of twins gave rise to moral and ethical problems often encountered in such situations, while one of the teratopagi was a unique case of a parasite projecting from the mouth of the normal twin.     

Sickle cell haemoglobin and glucose-6-phosphate dehydrogenase deficiency among Rellis of Visakhapatnam, Andhra Pradesh, South India

Sickle cell haemoglobin and glucose-6-phosphate dehydrogenase deficiency have been investigated in two endogamous subgroups of the Rellis, a scheduled caste population of Visakhapatnam of Andhra Pradesh (South India). The frequency for the sickle cell gene is higher among Relli-I (0.1216) than in Relli-II (0.0454). The incidence of G-6-PD deficiency is higher among Relli-II (0.0454) than in Relli-I (0.0328). The results were also compared with those available from other Andhra Pradesh populations.     

Importance of glucose-6-phosphate dehydrogenase activity for cell growth

The intracellular redox potential, which is determined by the level of oxidants and reductants, has been shown to play an important role in the regulation of cell growth. The principal intracellular reductant is NADPH, which is mainly produced by the pentose phosphate pathway through the actions of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, and by 6-phosphogluconate dehydrogenase. Previous research has suggested that an increase in G6PD activity is important for cell growth. In this article, we suggest that G6PD activity plays a critical role in cell growth by providing NADPH for redox regulation. The results show the following: 1) inhibition of G6PD activity abrogated growth factor stimulation of [3H]thymidine incorporation in all cell lines tested; 2) overexpression of G6PD stimulated cell growth, as measured by an increase in [3H]thymidine incorporations as compared with cells transfected with vector alone; 3) inhibition of G6PD caused cells to be more susceptible to the growth inhibitory effects of H2O2; 4) inhibition of G6PD led to a 30-40% decrease in the NADPH/NADP ratio; and 5) inhibition of G6PD inhibited cell anchorage and significantly decreased the growth-related stimulation of tyrosine phosphorylation.     

Glucose-6-phosphate dehydrogenase deficiency with psychosis

Several authors have attempted to establish a correlation between glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and chronic schizophrenia, and the results were contradictory. We propose that the correlation between G-6-PD deficiency and schizophrenia is to be found in the form of an acute delirium.