ZAP-70 mutation: a case with familial autoimmune haemolytic anaemia and immune deficiency.

Zeta-chain associated protein kinase 70 kDa (ZAP-70) deficiency is one of the rare immunodeficiency disorders due to autosomal recessive homozygous or compound heterozygous loss-of-function mutations in the ZAP-70 GENE In the literature, patients with ZAP-70 deficiency have been reported with a broad spectrum of clinical manifestations including recurrent respiratory infections (81.8%), cutaneous involvement (57.9%), lymphoproliferation (32.4%), autoimmunity (19.4%), enteropathy (18.4%) and increased risk of malignancies (8.1%). The most common immunological phenotype in those patients was low CD8+ T cell counts (97.9%) and normal non-functioning CD4+ T cell. Haematopoietic stem cell transplantation was applied as a curative treatment for this disorder.

Transfusion of blood components in pediatric age groups: an evidence-based clinical practice guideline adapted for the use in Egypt using 'Adapted ADAPTE'.

Pediatric transfusion is a complex area of medicine covering a wide age range, from neonates to young adults. Compared to adult practice, there is a relative lack of high-quality research to inform evidence-based guidelines. We aimed to adapt the pre-existing high-quality practice guidelines for the transfusion of blood components in different pediatric age groups to be available for national use by general practitioners, pediatricians, and other health care professionals. The guideline panel included 17 key leaders from different Egyptian institutions. The panel used the Adapted ADAPTE methodology. The panel prioritized the health questions and recommendations according to their importance for clinicians and patients. The procedure included searching for existing guidelines, quality appraisal, and adaptation of the recommendations to the target context of use. The guideline covered all important aspects of the indications, dosing, and administration of packed red cells, platelets, and fresh frozen plasma. It also included transfusion in special situations, e.g., chronic hemolytic anemia and aplastic anemia, management of massive blood loss, malignancies, surgery, recommendations for safe transfusion practices, and recommendations for modifications of cellular blood components. The final version of the adapted clinical practice guideline (CPG) has been made after a thorough review by an external review panel and was guided by their official recommendations and modifications. A set of implementation tools included algorithms, tables, and flow charts to aid decision-making in practice. This adapted guideline serves as a tool for safe transfusion practices in different pediatric age groups.

Mitochondrial 3-hydroxymethylglutaryl-CoA synthase-2 (HMGCS2) deficiency: a rare case with bicytopenia and coagulopathy.

Mitochondrial 3-hydroxymethylglutaryl-CoA synthase-2 (HMGCS2) is the main enzyme involved in ketogenesis. It is an essential enzyme for the catalysis of ß-oxidation-derived-acetyl-CoA and acetoacetyl Co-A to produce ß-hydroxy-ß-methylglutaryl-CoA (HMG-CoA) and free coenzyme A.The deficiency of this enzyme (3-hydoxy-3-methylglutaryl-CoA synthase) is a very rare metabolic disorder with limited cases described in the literature. The manifestations of this disease include hypoketotic hypoglycaemia, metabolic acidosis, lethargy, hepatomegaly with fatty liver and encephalopathy.We report a middle childhood male who presented with hepatosplenomegaly, lymphadenopathy and bicytopenia. The case was diagnosed by the whole exome sequencing which revealed a homozygous missense variant of uncertain significance in HMGCS2 gene.

Sickle cell disease: combination new therapies vs. CRISPR-Cas9 potential and challenges - review article.

In 2022, sickle cell disease (SCD) continues to affect the lives of millions of people, being one of the most frequently inherited blood disorders worldwide. Recently, several new therapies have been FDA approved for the treatment of SCD. The complexity of the pathophysiology of sickling has given opportunity to the evolution of several modalities of therapies. Nonetheless, the potential for complementary targeting of HbS polymerization, vasocclusion, and other inflammatory pathways remains controversial. None of these drugs can be considered a single curative line of treatment. With the advancement of CRISPR/Cas9 technology, autologous transplant of gene-edited hematopoietic stem cells could possibly provide a cure for most patients with SCD. The advantage of this approach over the conventional stem cell transplantation is that it decreases the need for immuno-suppressive drugs and the risk of graft-versus-host disease. In addition, recent technological advances can reduce the off-target effects, but long-term monitoring is needed to ensure the reliability of these methods in the clinical setting. This review explores the efficacy and safety of combination therapies and contrasting this alternative with the challenges that exist with sickle cell gene therapy using CRISPR.

The association between growth differentiation factor-15, erythroferrone, and iron status in thalassemic patients.

BACKGROUND: Iron overload can result in grave consequences in thalassemic patients, despite the availability of iron chelators. Therefore, alternative pathways aiming to reduce iron toxicity are currently investigated. Among which, reduction of iron absorption through control of hepcidin production appears to be promising. In this study, we investigated growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) as potential suppressors of hepcidin. METHODS: This cross-sectional study was conducted on 61 thalassemic patients and 60 healthy controls. The frequency of GDF15 gene polymorphism (rs4808793) (-3148C/G), serum level of GDF15 and erythroferrone were measured and correlated with those of hepcidin and serum ferritin. RESULTS: The presence of GDF15 gene mutations were significantly higher in the patients' group compared to controls (P value 0.035). Also, thalassemia patients had significantly higher levels of GDF15 and ERFE and lower hepcidin levels than controls (P value < 0.001). Serum hepcidin level showed significantly negative correlations with GDF15, ERFE, reticulocyte count, LDH level, and serum ferritin. Contrarily, it had highly significant positive correlation with hemoglobin. CONCLUSIONS: High level of GDF15 and/or ERFE may inhibit hepcidin production and increase iron load in patients with thalassemia; therefore, medications that suppress their actions may provide new therapeutic potentials for iron toxicity. IMPACT: Iron overload continues to be a major contributor to high morbidity and mortality in patients with thalassemia. New strategies together with proper chelation, need to be developed to minimize the effect of iron toxicity. Growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) inhibit hepcidin production and increase iron levels in conditions with ineffective erythropoiesis. Medications that suppress the production or interfere with the action of GDF15 or ERFE may represent new therapeutic potentials for iron toxicity. Prevention of iron toxicity will significantly reduce morbidity and mortality and improve the quality of life of thalassemia patients.

Impact of Superoxide Dismutase Genetic Polymorphism (SOD2 Val16Ala) and Superoxide Dismutase Level on Disease Severity in a Cohort of Egyptian Sickle Cell Disease Patients.

Background: Oxidative stress plays a pivotal role in the pathophysiology of sickle cell disease (SCD) and its associated disease complications. Superoxide Dismutases (SODs) are protective enzymes against oxidative stress. SOD2 deficiency results in the accumulation of oxidized red cell proteins, increased rate of hemoglobin oxidation, decreased red cell membrane deformability, and subsequently decreased red cells survival. Objective: The current study was designed to determine the effect of SOD2 Val16Ala gene polymorphism (rs4880) on SOD2 level and their possible impact on SCD disease severity in a cohort of Egyptian SCD patients. Methods: Genotyping SOD2 Val16Ala polymorphism by TaqMan allelic discrimination assay for hundred SCD patients and a hundred age-sex matched healthy controls revealed the genotypic and allelic frequencies of the studied polymorphism in the SCD patients were close to that of the controls. Results: Serum SOD2 level was significantly lower in those having the polymorphic genotypes (p=0.005). SOD2 level inversely correlates with the annual rate of hospitalization (r=-0.023, p= 0.038). Conclusion: SOD2 Val16Ala polymorphism was associated with low serum SOD2 level that may predict disease severity.

SARS-CoV-2 antibody seroprevalence rates among Egyptian blood donors around the third wave: Cross-sectional study.

Background: Seroprevalence studies may provide a more representative situation of the disease burden and population-level immunity in a country. Aim: The aim of this study was to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies among asymptomatic blood donors attending the Cairo University blood bank services at various points in time around the third wave. Methods: This cross-section study included 3058 eligible blood donors, representing a demographically and socially heterogeneous healthy population and categorized as: Group 1, 954 donors in the period from March 20 to 30/2021; Group 2, 990 donors in the period from June 3 to 10/2021. These two groups were tested for IgG against SARS-CoV-2 nucleocapsid antigen (NC) to detect qualitative reactivity. Group 3, 1114 donors in the period from July 20 to 30/2021 were tested by the SARS-CoV-2 IgG II Quant assay for the quantitative detection of IgG antibodies, including neutralizing antibodies (antispike antibodies). Results: Donors' age ranged between 18 and 59 (mean 33.9 ± 9) years. There was no significant correlation between seroprevalence and gender, area of residence, ABO or Rh blood types, and occupation or education. Antibody prevalence was found to be 13.2% in Group 1, 19.2% in Group 2 (overall 16.2%), and 66% in Group 3. There were only 49 included cases vaccinated against COVID-19. Conclusion: We concluded that the significant increasing trend in seroprevalence rates during the third wave, March, June, and July, in Egypt, reflects a high cumulative incidence of seroconversion that mirrored the epidemic curve in its rise, fall, and nadir.

The Cause-Effect Dilemma of Hematologic Changes in COVID-19: One Year after the Start of the Pandemic.

COVID-19 is a systemic infection that leads to multisystem affection, including hematological changes. On the other hand, the patients who have certain hematological diseases are more susceptible to COVID-19 infection. The aim of this review is to examine the wide spectrum of hematological changes that are reported to occur due to COVID-19 infection. Most of the studies over the past year mainly show that most of these changes are mainly non-specific, but are of prognostic value. On the other hand, the susceptibility of hematological patients to COVID-19 infection and complications remains questionable. Patients with certain hematological diseases (including malignancy) and those who are treated by aggressive immunosuppressive therapy have shown higher rates of COVID-19 infection and complications. On the other hand, for most of the patients suffering from other chronic hematological conditions, no evidence has shown a greater risk of infection, compared to the general population.

Bone health in pediatric transfusion-dependent beta-thalassemia: Circulating osteoprotegerin and RANKL system.

INTRODUCTION: While the mechanism of bone disease in thalassemia is multifactorial and still under investigation, the receptor activator of nuclear factor kappa B (RANK), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) have pivotal roles in regulating bone metabolism. This study aimed to measure RANKL and OPG serum levels, and to detect the incidence of RANKL rs9533156, OPG rs2073618, and OPG rs2073617 genotypes in pediatric ß-thalassemia patients and to assess their relation to bone mineral density. METHODS: Sixty patients with transfusion-dependent ß-thalassemia (TBT) patients ages 5 to 14 years were included, and 60 healthy, age- and sex-matched volunteers contributed as a control group. The patients were scanned for bone mineral density. RESULTS: The mean of spine dual-energy X-ray absorptiometry (DXA) Z-score in patients was -1.66 ± 1.02 standard deviation (SD). Twenty-four of them had low spine DXA Z-scores. The patients showed significantly lower OPG levels and OPG/RANKLs ratios than the control group (3.28 ± 9.11 ng/ml and 11.38 ± 14.93 ng/ml, and 0.01 ± 0.03 and 0.07 ± 0.09, respectively). The RANKL SNP rs9533156 TC heterozygous genotype was detected more with statistical significance in patients than controls. The incidence of OPG rs2073618 and OPG rs2073617 genotypes were 2.3 times and 1.9 times more frequent in patients than controls, respectively. CONCLUSION: The RANK/RANKL/OPG system may have an important role in regulating bone metabolism in TBT patients, although further studies are needed to clarify its role.

Prevalence and risk factors of cognitive impairment in children with sickle cell disease in Egypt.

Little is known about cognitive impairment in patients with sickle cell disease in Africa. This study aimed to assess cognitive impairment and identify possible risk factors in patients with sickle cell disease in Egypt. This study was conducted at Cairo University Children Hospital. Patients with sickle cell disease, between ages of 6-20 years were enrolled. Cognitive ability was tested using the Stanford Binet intelligence quotient (IQ) test, fourth edition. Transcranial Doppler, magnetic resonance imaging and magnetic resonance angiography of the brain were performed within a week of the IQ test. Among the 40 enrolled patients, 55% had a Full Scale IQ at least 1 standard deviation below the mean, and 27.5% had an IQ 2 standard deviations below the mean. High lactate dehydrogenase was significantly associated with low IQ (p = 0.004). In univariate analyses, IQ was significantly correlated with older age (p = 0.025), high lactate dehydrogenase (p = 0.008) and older age at the start of hydroxyurea (p = 0.025). Impaired cognition is prevalent among sickle cell disease patients. Early initiation of hydroxyurea therapy, which should also reduce hemolysis and lactate dehydrogenase, may be a simple measure to preserve mental abilities in these patients.

Comparing different markers of tubular dysfunction in transfusion-dependent thalassemia patients.

BACKGROUND: Renal tubular dysfunction was reported in transfusion-dependent thalassemia (TDT) patients and ranges from mild to severe. The objectives of our study were identification of the best marker of early renal tubular dysfunction in TDT patients among the three most commonly used urinary biomarkers, named neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein (RBP) and N-acetyl-D-glucosaminidase (NAG) and correlation of these biomarkers with different patient variables. METHODOLOGY: Sixty-one TDT patients and another 62 healthy children were enrolled in a cross-sectional study. Morning urine samples were taken for measurement of calcium, phosphorus, creatinine, microalbumin and markers of tubular dysfunction (NGAL, NAG and RBP). Urine NGAL/creatinine (UrNGAL/Cr), urine NAG/creatinine (UrNAG/Cr) and urine RBP/creatinine (UrRBP/Cr) ratios were used for accuracy. Patients were classified into 2 groups: group A, with tubular dysfunction and group b, without tubular dysfunction. RESULTS: Group A showed statistically significant higher UrNGAL/Cr (p < 0.001), UrRBP/Cr (p < 0.001) and UrNAG/Cr (p <0.001) than group B. In group A, microalbuminuria was detected only in 7 patients (28%) while it was detected in 12 patients (33.3%) in group B. By using ROC curve analysis, the diagnostic cutoff values for UrNGAL/Cr, UrRBP/Cr and UrNAG/Cr were 3713.38, 1614.85 and 56.56 ng/g, respectively. We found a statistically significant superiority of UrNGAL/Cr over UrRBP/Cr (p < 0.001) and UrRBP/Cr over UrNAG/Cr (p < 0.001). CONCLUSION: Evaluation of UrNGAL/Cr, UrRBP/Cr and UrNAG/Cr could early discriminate tubular dysfunction TDT patients from those with normal tubular function. UrNGAL/Cr is more accurate in early detection of tubular dysfunction when compared with the other two biomarkers.

Consensus Meeting Report "Technology Enhanced Assessment" in Covid-19 Time, MENA Regional Experiences and Reflections.

PURPOSE: Majority of the assessments, appraisals and placements have been disturbed, with some being cancelled, postponed, or modified in design. New approaches for assessment should be well-thought-out. This work attempts at capturing the collective wisdom of educators in the Middle East and North Africa region (MENA), providing an understanding of the online assessment conceptual framework in the era of COVID-19 that tells the story rather than determining cause and effect, and identifying the biggest gaps that derail the digital transformation. METHODS: A qualitative inductive study using the grounded theory approach was implemented following a synchronous virtual online meeting, a summary of the reflections as well as experiences of medical education experts was prepared. Data for this qualitative study were collected from the meeting. The meeting was video-recorded and transcribed by the researchers. Thematic analysis was performed by three separate researcher coders. The authors then discussed together until they reached a consensus. RESULTS: Three main thematic areas were identified: 1) feasibility, 2) exam fairness/equity and 3) acceptable graduate attributes, society/community acceptance. CONCLUSION: The COVID-19 era necessitated revisiting of our assessment strategies to cope with new changes within the available context. Rapid adaptation is required.

Premenstrual Syndrome and Its Impact on the Quality of Life of Female Medical Students at Bisha University, Saudi Arabia.

OBJECTIVE: The severity and chronicity of PMS can lead to the impairment of studies, and it can also affect relationships, activities, quality of life (QoL), and academic performance. This study aimed to determine PMS frequency and its associated factors in order to assess the quality of life (QoL) among female medical students at Bisha University, Saudi Arabia. METHODS: This study was cross-sectional and included 388 female medical students in the Faculty of Medical Applied Sciences and the Faculty of Medicine at Bisha University. The participants all filled in a self-administered questionnaire. The Premenstrual Syndrome Scale (PSS) was used based on the diagnostic and statistical criteria for PMS assessment. PMS was diagnosed after the presence of five or more severe premenstrual symptoms had been resolved following menstruation (adapted from American Psychiatric Association). DATA ANALYSIS: The data obtained were analyzed using SPSS 25.0. A chi-square test was used to test the associations between the study variables. A logistic regression analysis technique was used to select the group of variables. Participants were asked to provide consent to participate in the study. IRB was obtained from the University of Bisha, College of Medicine. RESULTS: The participants were aged 19.5 ± 4.9 years, and the prevalence of PMS was 64.9%. Most of the female students were of extroverted personality types (35%). In addition, 13.4% were obese or overweight, and 19.5% of the 50% with PMS exercised regularly (p < 0.05). Menstruation significantly influenced the related quality of life subscales (p < 0.05). CONCLUSION: PMS significantly influenced daily activities related to quality of life and homework. Moreover, almost half of the female students experienced the effects of menstruation in their learning environment. Therefore, among female students, the modification of risk factors should be considered a critical intervention point.

A guide for evaluation of online learning in medical education: a qualitative reflective analysis.

BACKGROUND: With the strike of Covid-19, an unprecedented rapid shift to remote learning happened worldwide with a paradigm shift to online learning from an institutional adjuvant luxury package and learner choice into a forced solo choice. This raises the question of quality assurance. While some groups have already established standards for online courses, teaching and programs yet very little information is included on methodology of their development and very little emphasis is placed on the online learning experience. Nevertheless, no work has been done specifically for medical education institutions. AIM: To develop a set of descriptors for best practice in online learning in medical education utilizing existing expertise and needs. METHODS: This work utilizes a qualitative multistage approach to identify the descriptors of best practice in online learning starting with a question guided focus group, thematic analysis, Delphi technique and an expert consensus session done simultaneously for triangulation. This was done involving 32 institution in 19 countries. RESULTS: This materialized into the development of a set of standards, indicators, and development of a checklist for each standard area. The standard areas identified were organizational capacity, educational effectiveness, and human resources each of which listed a number of standards. Expert consensus sessions identified the need for qualification of data and thus the development of indicators for best practice. CONCLUSION: Standards are needed for online learning experience and their development and redesign is situational and needs to be enhanced methodologically in axes that are pertaining to the needs of the education community. Taking such axes into consideration by educators and institutions will lead to planning and implementing successful online learning activities, while taking them into consideration by the evaluators will help them conduct comprehensive audits and provide stakeholders with highly informative evaluation reports.

The potential hepatoprotective effect of metformin in hepatitis C virus-infected adolescent patients with beta thalassemia major: Randomised clinical trial.

BACKGROUND: Iron overload-induced oxidative stress and transfusion-acquired hepatitis C virus (HCV) infection are the main reasons of liver damage in beta thalassemia major (ß-TM). OBJECTIVES: Based on metformin's hepatic benefits in nondiabetic populations, the study aims to investigate the safety and the potential hepatoprotective effect of metformin in HCV-infected ß-TM adolescent patients. METHODS: This was a prospective, randomised, parallel, controlled, open-label study in which 60 HCV-infected ß-TM adolescent patients aged 11 to 18 years and receiving no antiviral therapy were selected and randomly assigned to treatment or control group in 1:1 allocation. Both groups were receiving ß-TM standard-of-care regimen, whereas metformin (500 mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed up for 6 months with assessment of liver biochemical profile, oxidative stress markers, liver fibrosis, clinical symptom improvement and metformin's adverse effects. RESULTS: Aspartate aminotransferase serum level decreased significantly over time in the treatment group only (P = .013). However, improvement was not clinically significant and did not attain normality. Change in total antioxidant capacity and malondialdehyde serum levels indicated significantly improved oxidative stress status in the treatment group versus significant deterioration in the control group (P < .001). Fibrosis grade improvement was observed in 14 patients in the treatment group versus one improved case in the control group. CONCLUSION: The use of metformin in HCV-infected ß-TM adolescent patients as an adjuvant antioxidant hepatoprotective agent is promising and can improve liver damage.

Intracranial hemorrhage in primary immune thrombocytopenia (ITP): 20 years' experience in pediatrics.

Incidence of intracranial hemorrhage (ICH) among children with primary immune thrombocytopenia (ITP) varies among different studies. We published data during the period of 1997-2007 of ICH in children with primary ITP, addressing risk factors and outcome. The aim of this study is to assess changes in incidence, risk factors, and outcome of ICH in children with ITP from last decade and to report the overall 20 years' experience. We compared 2008-2018 with the decade before it. Data of children with ITP and ICH during study period and ITP control cases were analyzed. Neurosurgical intervention and outcome were also reported. A total of 4340 children with primary ITP were evaluated. Twenty-five (0.63%) ICH events were reported over 2 decades. Head trauma, hematuria, and platelet counts < 10 × 109/L were the risk factors mostly associated with ICH. Overall mortality was 24%, and a further 28% had neurologic sequelae. Neurosurgical intervention was done in 12% of cases with good outcome.Conclusion: Persistent platelet counts < 10 × 109/L were a significant risk factor for ICH in both time periods, while head trauma and hematuria were more reported in the period of 2008-2018 as significant risk factors for ICH. Outcome was comparable in both periods. What is Known: • ICH is a rare complication of ITP; however, early recognition of risk factors and aggressive treatment might lead to complete recovery without sequalae. Platelet counts less than < 10 × 109/L are the main risk factor for ICH. Few studies reported other significant risk factors. What is New: • Hematuria and head trauma are significant risk factors for ICH in ITP, in addition to having a persistently low platelet count < 10 × 109/L. (more than 90 days in chronic ITP, 45 days in persistent and 21 days in acute ITP) • Combined treatment with IVIG and HDMP followed by platelet transfusion was associated with complete recovery without sequelae in almost 50% of patients.

Right ventricular functions in subphenotypes of sickle cell disease.

OBJECTIVES: Sickle cardiomyopathy is the most important cause of death in patients with sickle cell disease (SCD). Based on recent evidence, SCD can be divided into two subphenotypes, namely, the viscosity vasoocclusion (VVO) subphenotype and the hemolysis endothelial dysfunction (HED) subphenotype. The aim of our series is to study right ventricular (RV) functions in both subphenotypes. METHODS: Echocardiography including conventional and tissue Doppler imaging as well as speckle tracking echocardiography was performed in 50 patients (23 from the VVO subgroup and 27 from the HED subgroup) based on a serum lactate dehydrogenase (LDH) level below or above 270 U/L, respectively, and in 50 controls. Reticulocyte count and hemoglobin levels were assessed in different groups of patients. RESULTS: The HED subgroup showed RV dysfunction. Patients in this subgroup also showed systolic and diastolic functions similar to those seen in the VVO subgroup and controls. In addition, a tight correlation exists between LDH and both RV global longitudinal strain (-0.68) and RV E/E' ratio (0.9), defined as the ratio of early diastolic tricuspid inflow velocity to tricuspid annular early diastolic velocity. CONCLUSIONS: Results reveal a marked discrepancy in RV functions between HED and VVO subphenotypes of SCD, with patients in the former subgroup being more prone to RV dysfunction. This warrants early screening of such patients in daily practice.

Prevalence of α-Thalassemia in the Egyptian Population.

Hemoglobinopathies are the most common monogenic diseases in the world, causing many health problems worldwide. In Egypt, thalassemia is the most common cause of chronic hemolytic anemia and correlated with significant morbidity and mortality. One thousand Egyptian newborns were screened to detect α-thalassemia (α-thal) deletions using polymerase chain reaction (PCR)-based DNA analysis of cord blood samples. Ninety-one cases (9.1%) of the studied samples were proved to have at least one of the α genes deleted and 851 cases (85.1%) were normal by PCR analysis, while 58 samples (5.8%) failed to be amplified so further DNA analysis could not be done. In the studied group with α gene deletions, we found different types including silent carriers with only one α-globin gene deleted (3.1%), α-thal trait with two α-globin genes deleted (4.2%), Hb H disease with three α-globin genes deleted (1.8%) and no cases carrying Hb Bart's disease with loss of four α-globin genes. We determined the deletional spectrum of α-thal, which might be used in the future for molecular investigations of the disease in susceptible patients in our population.

ßS globin gene haplotype and the stroke risk among Egyptian children with sickle cell disease.

BACKGROUND AND AIM OF WORK: Sickle cell disease (SCD) is an inherited disease of the beta globin gene. The ßS globin gene haplotypes are Senegal, Benin, Bantu, Cameroon, Arab-Indian and atypical haplotypes. In SCD, stroke is a life-threatening event in both adults and children. In light of paucity of studies on ßS globin gene haplotypes in Egypt, we aimed to determine ßS globin gene haplotypes in children with SCD and study their impact on stroke risk. METHODS: Fifty-two SCD patients were included in the study, they were 26 males and 26 females with age range from 3 to 18 years old. The PCR-RFLP technique was used for the determination of ßS globin gene haplotypes. Transcranial Doppler (TCD) was done to identify patients at risk of stroke. RESULTS: Benin/Benin was the most prevalent haplotype detected in 50% followed by Benin/Bantu in 30.8% of studied patients. TCD study showed that 14/52 (26.9%) patients had abnormally high TCD flow velocities (TCD velocities ≥170 cm/s) and thus considered high stroke risk group, whereas 38/52 (73.1%) patients had TCD flow velocities <170 cm/s and are considered low stroke risk group. Stroke risk was not found to be associated with ßS globin gene haplotype (p = .532). CONCLUSION: This study provides a relevant contribution to our understanding of the anthropological and historical background of the population in Egypt where Benin haplotype is the commonest ßS globin gene haplotype and homozygous Benin/Benin is associated with higher stroke risk than other haplotypes.

Enhancing Effect of Hydroxyurea on Hb F in Sickle Cell Disease: Ten-Year Egyptian Experience.

Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r = 0.4, p = 0.04; r = 0.45, p = 0.001; r = 0.5, p = 0.019, respectively) and inversely correlated with baseline total leucocyte count (r = -0.33, p = 0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p = 0.009, p = 0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p = 0.00, p = 0.03, p = 0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.