Clinical Significance of G6PD Variants among Palestinians

Conclusion: We conclude that children with G6PD A-deficiency are also susceptible to AHA, but demonstrate in direct comparison within this same population that G6PD Mediterranean and G6PD Cairo are more severe forms of deficiency than G6PD A‐. Further, we show that the heretofore poorly studied G6PD Cairo may be associated with low‐level, chronic hemolysis. This study illustrates favism is a significant public health problem in Gaza due to fava beans as a staple in the diet and the coexistence of polymorphic G6PD deficiency variants in the society. Favism is an easily preventable and manageable genetic disorder with the proper awareness, intervention and education programs

Should sex differences be considered when applying mathematical indices and formulas for discriminating β- thalassemia minor from iron deficiency?

Background: β-thalassemia minor (BTM) and iron deficiency (ID) are common disorders characterized by microcytosis and/or hypochromasia, leading to a challenge in their discrimination during mass-screening programs especially in developing countries where resources are limited. It has been shown with varying reliability that quick exclusion of either disorder could be achieved mathematically using RBC-based indices and formulas. However, none of these proposed indices and formulas considered the sex-based hematological differences. This comparative retrospective study examined the efficacy of using sex-based RBC indices in the mathematical discrimination BTM and ID in adult males and females. Methods: The CBC of randomly selected eight hundred adults diagnosed with BTM or ID (200M & 200F BTM, and 200M & 200F ID) were used in the comparisons. The discrimination power, in terms of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and Youden index were calculated for all subjects and separately for males and females for 20 mathematical indices and formulas. Results: Data revealed significant differences in the RBC-based indices between males and females for both BTM and ID groups. Significant variation in reliability indicators for the different indices and formulas were discovered between males and females samples. Conclusion: Sex-based indices and formulas are necessary to improve the reliability in mathematically discriminating between BTM and ID in mass screening programs. We also advocate for a large–scale multicenter study to establish the parameters of such indices and formulas with sex and age. Keywords: β-thalassemia minor, Iron deficiency, Mathematical indices and formulas, Discrimination power, Sensitivity, Specificit

Homocysteine and vitamin B 12 status and iron deficiency anemia in female university students from Gaza Strip, Palestine

OBJECTIVE: Nutritional deficiencies are very significant to the overall health of humans at all ages and for both genders, yet in infants, children and women of childbearing age these deficiencies can seriously affect growth and development. The present work is aimed to assess homocysteine and vitamin B12 status in females with iron deficiency anemia from the Gaza Strip.METHODS: Venous blood samples were randomly collected from 240 female university students (18-22 years old) and parameters of the complete blood count, serum ferritin, homocysteine and vitamin B12 were measured. Statistical analysis included the t-test and analysis of variance (ANOVA) using the IBM SPSS software (version 18). Statistical significance was set for p-values <0.05.RESULTS: The results revealed that 20.4% of the students have iron deficiency anemia. The mean serum vitamin B12 level in females with iron deficiency anemia (212.9 ± 62.8 pg/mL) was significantly lower than in normal controls (286.9 ± 57.1 pg/mL) and subjects with microcytic anemia and normal ferritin (256.7 ± 71.1 pg/mL). Significantly higher serum homocysteine levels were reported in the iron deficiency anemia group (27.0 ± 4.6 µmol/L) compared to normal controls (15.5 ± 2.9 µmol/L) and in subjects with microcytic anemia and normal ferritin (18.1 ± 2.7 µmol/L). Statistically significant negative correlations were reported for serum homocysteine with serum ferritin, vitamin B12, hemoglobin, and hematocrit levels.CONCLUSION: Important associations were found between serum homocysteine and markers of iron deficiency. Monitoring homocysteine levels might be essential to understand the development of different clinical conditions including anemia. It seems necessary to conduct prospective trials to determine whether treating anemia ameliorates homocysteine levels

Genotype-phenotype characteristics of β thalassemia children in the Gaza Strip, Palestine

Methods Blood samples were collected just before scheduled blood transfusion from 53 β-thalassemic children who are already characterized for the causative mutation. Blood samples were collected also from 53 apparently healthy children of the same sex and age range. Complete blood count and biochemical tests were performed

Possible association of 3′ UTR+ 357 A> G, IVS11-nt 93 T> C, c. 1311 C> T polymorphism with G6PD deficiency

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon–intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. Objectives: Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. Methods: Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. Results: In our Palestinian

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

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common genetic abnormality known to predispose to acute hemolytic anemia (AHA), which can be triggered by certain drugs or infection. However, the commonest trigger is fava beans (Vicia faba) ingestion, causing AHA (favism), which may be life-threatening especially in children. G6PD deficiency is genetically highly heterogeneous, as nearly 200 different mutations have been observed. We have investigated the hematological features of acute favism in the Palestinian Gaza community that is characterized by the polymorphic coexistence of three different G6PD deficiency genes (G6PD A−, G6PD Cairo, G6PD Med). We have found by comparison to the general population (485 adults and 466 newborns) that children with favism, in terms of relative frequency, G6PD A− was under-represented, whereas G6PD Med was over-represented. We also found

Genetic Variants of Glucose-6-Phosphate Dehydrogenase and Their Associated Enzyme Activity: A Systematic Review and Meta-Analysis.

Low glucose-6-phosphate dehydrogenase enzyme (G6PD) activity is a key determinant of drug-induced haemolysis. More than 230 clinically relevant genetic variants have been described. We investigated the variation in G6PD activity within and between different genetic variants. In this systematic review, individual patient data from studies reporting G6PD activity measured by spectrophotometry and corresponding the G6PD genotype were pooled (PROSPERO: CRD42020207448). G6PD activity was converted into percent normal activity applying study-specific definitions of 100%. In total, 4320 individuals from 17 studies across 10 countries were included, where 1738 (40.2%) had one of the 24 confirmed G6PD mutations, and 61 observations (3.5%) were identified as outliers. The median activity of the hemi-/homozygotes with A-(c.202G>A/c.376A>G) was 29.0% (range: 1.7% to 76.6%), 10.2% (range: 0.0% to 32.5%) for Mahidol, 16.9% (range 3.3% to 21.3%) for Mediterranean, 9.0% (range: 2.9% to 23.2%) for Vanua Lava, and 7.5% (range: 0.0% to 18.3%) for Viangchan. The median activity in heterozygotes was 72.1% (range: 16.4% to 127.1%) for A-(c.202G>A/c.376A>G), 54.5% (range: 0.0% to 112.8%) for Mahidol, 37.9% (range: 20.7% to 80.5%) for Mediterranean, 53.8% (range: 10.9% to 82.5%) for Vanua Lava, and 52.3% (range: 4.8% to 78.6%) for Viangchan. A total of 99.5% of hemi/homozygotes with the Mahidol mutation and 100% of those with the Mediterranean, Vanua Lava, and Viangchan mutations had A/c.376A>G), 55% of hemi/homozygotes had <30% activity. The G6PD activity for each variant spanned the current classification thresholds used to define clinically relevant categories of enzymatic deficiency