G6PD Deficient Variants Differ in Risk of Hospitalization Among Gaza Strip Palestinian Children

Abstract Abstract 4268 Glucose-6-phosphate dehydrogenase (G6PD) deficiency, affecting more than 500 million people worldwide, is one of the most common inherited disorders. There are 186 G6PD mutations published, with some that cluster within defined ethnic/racial groups, and in some populations more than one variant is encountered. These prevalent variants are generally considered to be benign in adults, but their morbidity, presenting as acute hemolytic anemia, in young children can be significant. However, comprehensive molecular characterization of ethnically prevalent G6PD mutants and their relative clinical significance is lacking. In a region where the frequency of G6PD deficiency in the population is significant (>3%) and fava beans, green and dried, are a dietary staple, the risk of acute hemolytic crisis is significant. We studied 80 consecutively hospitalized unrelated Gaza Strip Palestinian children (ages 34–52 months, mean=39.5) for acute hemolytic anemia and found G6PD deficiency accounted for most cases (65 of 80 children; 81%) and almost all occurred after ingestion of green fava beans. Molecular analyses revealed 5 separate mutations, with 3 accounting for most cases. These were G6PD Mediterraneanc.563T, African G6PD A-c.202A/c.376G, and G6PD Cairoc.404C with relative allele frequencies of 0.33, 0.26, and 0.18 respectively. The detection of G6PD Cairo in 14 unrelated hospitalized children was surprising as this variant was encountered previously only in a single Egyptian individual. This unanticipated molecular heterogeneity of G6PD variants among Gaza Strip Palestinians provided a unique opportunity to test their relative clinical significance. We compared the prevalence of these variants to a control group consisting of 466 self-reported healthy, non-anemic, unrelated Palestinian adults (46 women and 420 men; 512 X-chromosomes). Within this cohort, the proportion with the G6PD deficient variants was 3.3%. The most common mutation was G6PD A+c.376A (allele frequency 0.016), comprising 47% of the variants detected while the G6PD variants Mediterranean and A- had allele frequencies of 0.0098 and 0.0078, respectively, comprising 29.4% and 23.5% of the detected variants. G6PD Cairo was not detected. The proportion of G6PD Mediterranean and G6PD A- variants in the general population are equivalent to their representation in the hospitalized children population. However, the number of G6PD Cairo variants in the hospitalized cohort was vastly larger than that observed in the general population indicating that these carriers are at a greater risk of hospitalization (Table 1). We found a dramatically increased risk of acute hemolytic anemia requiring hospitalization associated with all three variants. Fisher's Exact test was used to determine the association between the risk of hospital admission and presence of the variants and was significant for all at p<0.0001. Additionally, odds ratios for hospitalization are 41.1 (for G6PD A-) and 70.0 (for G6PD Mediterranean) compared to wild type [odds ratio was infinite for G6PD Cairo since it was not detected in the healthy population]. This is the first study comparing the relative clinical impact of three prevalent G6PD deficient variants in the same population and habitat to identify clinically significant effects due to the different genetic mutations. Table 1: Distribution of G6PD variants in Gaza among hospitalized children vs. general Gaza population G6PD Mediterranean A- Cairo + - + - + - Hospitalized children 26 54 21 59 14 66 Healthy population 3 463 4 462 0 466 Odds ratio (95% CI) 70.0 (20.1–367.4) 41.1 (13.1–168.2) ∞ Fisher's Exact p-value <0.0001 <0.0001 <0.0001 Confidence interval (CI) -NSR and MMS contributed equally to this work. Disclosures: No relevant conflicts of interest to declare.

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Favism, the commonest form of severe hemolytic anemia in Palestinian children, varies in severity with three different variants of G6PD deficiency within the same community

Blood Cells Molecules and Diseases ◽

10.1016/j.bcmd.2016.07.001 ◽

2016 ◽

Vol 60 ◽

pp. 58-64 ◽

Cited By ~ 5

Author(s):

N. Scott Reading ◽

Mahmoud M. Sirdah ◽

Mohammad E. Shubair ◽

Benjamin E. Nelson ◽

Mustafa S. Al-Kahlout ◽

...

Keyword(s):

Hemolytic Anemia ◽

G6pd Deficiency ◽

Palestinian Children

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Favism Induced Methemoglobinemia in G6DP Deficient Patients: Case Series and Review of Literature

Blood ◽

10.1182/blood-2020-137614 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 11-12

Author(s):

Fateen Ata ◽

Bassam Muthanna ◽

Saad Javed ◽

Mashuk Uddin ◽

Mohamed A Yassin

Keyword(s):

Oxidative Stress ◽

Methylene Blue ◽

Vitamin C ◽

Hemolytic Anemia ◽

G6pd Deficiency ◽

The Body ◽

Oxidative Hemolysis ◽

Fava Bean ◽

History Of ◽

Fava Beans

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a well-known cause of hemolysis. It has a notable prevalence in African, Asian, and Mediterranean countries. Favism is a common trigger of oxidative stress in G6PD deficient people, which can lead to hemolysis. Additionally, fava bean ingestion can cause methemoglobinemia (MethHgb), an abnormal variation in the Hgb in which the ferrous (Fe2+) iron in heme is oxidized to the ferric (Fe3+) state. It is rare to have both G6PD deficiency and MethHgb secondary to favism at the same time. The first-line treatment for MethHgb is methylene blue. However, in G6PD deficient patients, it can potentiate hemolysis. Methods: We reviewed the literature using PubMed and Google scholar and found 6 cases of MethHgb secondary to favism in patients with G6PD deficiency. We also analyzed two cases which are still unpublished, making a total of 8 cases. Results: All 8 cases were male with median age of 18 years (1 - 56). 1 patient had a prior diagnosis of G6PD deficiency while 7 were newly diagnosed. Median Hgb was 8.3gm/dL (4.6 - 12.5) and median MetHgb was 7.8 % (3.5 - 35). 1 patient received methylene blue, and 4 received Vitamin C. All of the patients recovered and were discharged [Table 1]. Unpublished case 1: A 56-year-old male presented with MethHgb and hemolytic anemia, secondary to fava bean ingestion. Hgb on admission and lowest recorded were 9.9 and 6.5 gm/dL, respectively. He had an SPO2 of 70% on room air and 101.2 % on ABG. Methylene blue administration worsened the hemolysis as he was G6PD deficient but not diagnosed before. He got better with discontinuation of methylene blue and Vitamin C and was discharged on day 5. Unpublished case 2: A 43-year-old male, known case of G6PD deficiency presented with MethHgb and hemolytic anemia, secondary to fava bean ingestion. Hgb on admission and lowest recorded were 12.5 and 7.4 gm/dL, respectively. He had an SPO2 of 82% on room air and 100 % on ABG. He received IV vitamin C and recovered and was discharged on day 4. Discussion: Methemoglobinemia is usually acquired, secondary to oxidative stress in the body, but can rarely be congenital. Enzyme systems such as NADH methemoglobin reductase, NADPH methemoglobin reductase, ascorbic acid, and glutathione reductase systems keep a check on the accumulation of methemoglobin in the blood. However, these mechanisms can be insufficient to counter the conversion of Hgb to MethHgb, consequently promoting an oxidative state in the body. It can be due to the overproduction of methemoglobin (secondary to exposure to certain drugs, chemicals, or food items, but can sometimes be hereditary) or under conversion to Hgb due to unavailable enzyme mechanisms. One of the causes of the inability to counteract methemoglobin can be secondary to G6PD deficiency. Patients with MetHgb have a low oxygen saturation (SPO2) on pulse oximeters but a falsely high SPO2 on arterial blood gasses (ABG). The treatment depends on symptoms and the level of MethHgb. The first step is to remove any possible precipitator if present. Symptomatic patients (and asymptomatic with a level of methemoglobin >30 %) are treated with methylene blue (1-2mg/kg), which is reduced to leuko-methylene blue via NADPH dependent methemoglobin reductase. This, in turn, reduces methemoglobin back to Hgb, correcting the abnormality [Figure 1]. Rarely, patients can present with co-occurrence of MethHgb and G6PD deficiency. In such cases, caution is required while giving methylene blue as they do not have sufficient levels of NADPH to reduce it. Otherwise, a cascade of oxidative hemolysis ensues secondary to underlying G6PD deficiency, resulting in a vicious cycle of further methemoglobinemia. The most frequent cause of this co-occurrence is the ingestion of fava beans, which can simultaneously induce MethHgb and potentiate G6PD deficiency. One of our patients had a history of favism without developing any symptoms. Only this time, he ate fava beans in a larger amount, leading to hemolysis and MethHgb. Conclusion: Favism is a rare cause of the co-occurrence of methemoglobinemia and hemolysis in G6PD deficient individuals. It is vital to identify G6PD deficiency in patients presenting with MethHgb, as the initiation of methylene blue in such individuals can result in a cascade of oxidative hemolysis. A history of fava beans ingestion without any symptoms does not rule out G6PD deficiency, as it is proportional to the number of beans ingested. Disclosures No relevant conflicts of interest to declare.

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Prevalence of Hallucinations in the General Croatian Population

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18084237 ◽

2021 ◽

Vol 18 (8) ◽

pp. 4237

Author(s):

Jelinčić Ivana ◽

Degmečić Dunja

Keyword(s):

General Population ◽

Clinical Significance ◽

Assessment Tool ◽

Visual Hallucinations ◽

The World ◽

The Mind

Background: Hallucinations involve sensing things such as visions, sounds, or smells that seem real but are not. These things are created by the mind. However, little is known about the distribution of incident hallucinations in the community. This paper aims to examine manifestation and frequency of the hallucinatory experiences within the general Croatian population. Methods: The instrument of the survey is Chicago Hallucination Assessment Tool (CHAT). The study included 521 examinees; 284 females (54.5%) and males 237 (45.5%). Results: There was a manifestation of all types of hallucinatory experiences determined. Out of all of the participants 17% listed that they experienced acoustic hallucinations during their lifetime, 15% said that they have experienced visual hallucinations, 12% olfactory hallucinations, 10% gustatory and 12% tactile/cenesthetic hallucinations. Conclusion: The results of this research have indicated that simple hallucinations were mostly represented among the general Croatian population and those more complex were represented less which is a positive thing because of its prominent clinical significance. The contribution of this study is the possibility of comparisons with studies from different regions of Europe and the world. This is another component in a better understanding of the incidence of hallucinations in the general population. The data we have obtained puts us on the map of countries trying to raise awareness of a topic that needs to acquire more attention.

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Symptoms of Depression in a Large Healthy Population Cohort are related to Subjective Memory Complaints and Memory Performance in Negative Contexts

10.1101/101642 ◽

2017 ◽

Cited By ~ 1

Author(s):

Susanne Schweizer ◽

Rogier A. Kievit ◽

Tina Emery ◽

Richard N. Henson ◽

Keyword(s):

Depressive Symptoms ◽

General Population ◽

Memory Performance ◽

Large Population ◽

Healthy Population ◽

Subjective Memory Complaints ◽

Subjective Memory ◽

Symptoms Of Depression ◽

Memory Complaints ◽

The Impact

AbstractDecades of research have investigated the impact of clinical depression on memory, which has revealed biases and in some cases impairments. However, little is understood about the effects of sub-clinical symptoms of depression on memory performance in the general population. Here we report the effects of symptoms of depression on memory problems in a large population-derived cohort (N = 2544), 87% of whom reported at least one symptom of depression. Specifically, we investigate the impact of depressive symptoms on subjective memory complaints, objective memory performance on a standard neuropsychological task and, in a subsample (n = 288), objective memory in affective contexts. There was a dissociation between subjective and objective memory performance, with depressive symptoms showing a robust relationship with self-reports of memory complaints, even after adjusting for age, gender, general cognitive ability and symptoms of anxiety, but not with performance on the standardised measure of verbal memory. Contrary to our expectations, hippocampal volume (assessed in a subsample, n = 592) did not account for significant variance in subjective memory, objective memory or depressive symptoms. Nonetheless, depressive symptoms were related to poorer memory for pictures presented in negative contexts, even after adjusting for memory for pictures in neutral contexts. Thus the symptoms of depression, associated with subjective memory complaints, appear better assessed by memory performance in affective contexts, rather than standardised memory measures. We discuss the implications of these findings for understanding the impact of depressive symptoms on memory functioning in the general population.

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Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase–deficient children receiving dapsone

Blood ◽

10.1182/blood-2012-03-416032 ◽

2012 ◽

Vol 120 (20) ◽

pp. 4123-4133 ◽

Cited By ~ 60

Author(s):

Allan Pamba ◽

Naomi D. Richardson ◽

Nick Carter ◽

Stephan Duparc ◽

Zul Premji ◽

...

Keyword(s):

Blood Transfusion ◽

Hemolytic Anemia ◽

G6pd Deficiency ◽

Case Reports ◽

Drug Induced ◽

Once Daily ◽

Maximum Decrease ◽

Life Threatening ◽

The Mean ◽

Glucose 6 Phosphate Dehydrogenase

AbstractDrug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging −2.64 g/dL (range −6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference −1.46 g/dL; 95% confidence interval −1.76, −1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was −1.83 g/dL (range +0.90 to −5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A− variant, ie, mutations V68M and N126D. Drug-induced acute hemolytic anemia in G6PD A− subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A− type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735.

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Severe-glucose-6-phosphate dehydrogenase (G6PD) deficiency associated with chronic hemolytic anemia, granulocyte dysfunction, and increased susceptibility to infections: description of a new molecular variant (G6PD Barcelona)

Blood ◽

10.1182/blood.v59.2.428.428 ◽

1982 ◽

Vol 59 (2) ◽

pp. 428-434 ◽

Cited By ~ 41

Author(s):

JL Vives Corrons ◽

E Feliu ◽

MA Pujades ◽

F Cardellach ◽

C Rozman ◽

...

Keyword(s):

Hemolytic Anemia ◽

G6pd Deficiency ◽

Specific Activity ◽

Heat Stability ◽

Molecular Characteristics ◽

Functional Studies ◽

Leukocyte Alkaline Phosphatase ◽

Severe Deficiency ◽

Glucose 6 Phosphate Dehydrogenase ◽

Increased Susceptibility

Abstract Molecular, kinetic, and functional studies were carried out on erythrocytes and leukocytes in a Spanish male with G6PD deficiency, congenital nonspherocytic hemolytic anemia (CNSHA), and increased susceptibility to infections. G6PD activity was absent in patient's red cells and was about 2% of normal in leukocytes. Molecular studies using standard methods (WHO, 1967) showed G6PD in the patient to have a slightly fast electrophoretic mobility at pH 8.0 with otherwise normal properties (heat stability at 46 degrees C, apparent affinity for substrates, optimum pH, and utilization of substrate analogues). Other tests showed the patient's granulocytes to engulf latex particles normally, but to have impaired reduction of nitroblue tetrazolium and ferricytochrome-c as well as reduced iodination. Chemotaxis and random migration of the patient's granulocytes were normal as were myeloperoxidase, leukocyte alkaline phosphatase (LAP), and ultrastructural features. The molecular characteristics of G6PD in the patient differed from those of all previously reported variants associated with CNSHA, so the present variant was provisionally called G6PD Barcelona to distinguish it from other G6PD variants previously described. Possible mechanisms for the severe deficiency of G6PD in erythrocytes and granulocytes was investigated by studies on the immunologic specific activity of the mutant enzyme.

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The P Value Problem in Otolaryngology: Shifting to Effect Sizes and Confidence Intervals

Otolaryngology ◽

10.1177/0194599816677735 ◽

2016 ◽

Vol 156 (6) ◽

pp. 978-980 ◽

Cited By ~ 7

Author(s):

Peter M. Vila ◽

Melanie Elizabeth Townsend ◽

Neel K. Bhatt ◽

W. Katherine Kao ◽

Parul Sinha ◽

...

Keyword(s):

General Population ◽

Confidence Intervals ◽

Clinical Significance ◽

Paradigm Shift ◽

Biomedical Literature ◽

Effect Sizes ◽

P Value ◽

P Values ◽

Population Mean

There is a lack of reporting effect sizes and confidence intervals in the current biomedical literature. The objective of this article is to present a discussion of the recent paradigm shift encouraging the use of reporting effect sizes and confidence intervals. Although P values help to inform us about whether an effect exists due to chance, effect sizes inform us about the magnitude of the effect (clinical significance), and confidence intervals inform us about the range of plausible estimates for the general population mean (precision). Reporting effect sizes and confidence intervals is a necessary addition to the biomedical literature, and these concepts are reviewed in this article.

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PREVALENCE OF CARPAL TUNNEL SYNDROME IN WORKERS FROM A FISHNET FACTORY IN THAILAND

Hand Surgery ◽

10.1142/s0218810405002565 ◽

2005 ◽

Vol 10 (01) ◽

pp. 67-70 ◽

Cited By ~ 5

Author(s):

Surut Jianmongkol ◽

Weerachai Kosuwon ◽

Ekamol Thumroj ◽

Sermsak Sumanont

Keyword(s):

Risk Factors ◽

At Risk ◽

Carpal Tunnel Syndrome ◽

General Population ◽

Carpal Tunnel ◽

Odds Ratio ◽

Office Workers ◽

Tunnel Syndrome ◽

Associated Risk Factors

We determined the prevalence of carpal tunnel syndrome (CTS) at a fishnet factory in order to discern the possible associated risk factors at this type of workplace. The 662 workers were interviewed then physically examined. The prevalence of CTS was 14.5%, which is significantly higher than in the general population. Workers directly involved in the production of fishnets had a significantly higher risk of CTS than the factory's office workers or housemaids (odds ratio = 1.84; range, 1.03–3.29; 95% CI, p = 0.049). There was no association between the length of employment in the factory with CTS (odds ratio = 1.13; range, 0.77–1.66; 95% CI, p = 0.591). Our results confirm that factory jobs with repetitive hyperflexing and twisting of the wrists are at risk of CTS.

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