Β-thalassemia Major Patients Research Articles

Renal Dysfunction in Pediatric Patients in Iraq With β-Thalassemia Major and Intermedia.

BackgroundWith optimum transfusion and chelation therapy, the survival of β-thalassemia patients and the incidence of various complications, including renal complications, have improved.ObjectivesTo investigate renal involvement in β-thalassemia patients using serum and urinary biochemical markers of glomerular and tubular dysfunction.MethodsThis case-control study included 69 β-thalassemia major (β-TM) patients, 23 β-thalassemia intermedia (β-TI) patients, and 100 healthy controls, all ranging from 1 to 16 years in age. Blood urea nitrogen (BUN), serum ferritin, serum and urinary levels of creatinine (Cr), uric acid (UA), calcium (Ca), phosphorus (Ph), magnesium (Mg), sodium (Na), and potassium (K), and the urinary albumin/creatinine ratio were evaluated.ResultsThe BUN level and the urinary Na/Cr, K/Cr, Ca/Cr, Mg/Cr, Ph/Cr, albumin/Cr, and UA/Cr ratios were significantly higher in the β-thalassemia patients than in the controls. In contrast, the serum Na, K, Ca, and Mg levels were significantly lower in the patients (P<0.05). An elevated urinary UA/Cr ratio was found in 61.9% of β-thalassemia patients, and an elevated urinary Ca/Cr, and urinary albumin/Cr ratio was found in 53.2%. An elevated Na/Cr ratio was found in 41.3%. The serum and urinary renal markers showed no significant differences between patients with β-TM and β-TI, except for microscopic hematuria, which was significantly higher in β-TI patients (34.8%) than in β-TM patients (13%), P>0.02. At an older age, high serum ferritin levels and deferoxamine therapy were associated with significant tubular and glomerular dysfunction in β-thalassemia patients.ConclusionsPediatric patients with β-thalassemia have significantly abnormal tubular and glomerular functions, necessitating early detection and monitoring to prevent/reverse renal function deterioration.

Cardiopulmonary testing in adult patients with β-thalassemia major in comparison to healthy subjects

β-Thalassemia patients often have a reduced capacity of exercise and abnormal respiratory function parameters, but the reasons are unclear. In order to identify the causes of the exercise limitation, we performed a cardiopulmonary exercise testing (CPET) in a group of 54 adult β-thalassemia major (TM) patients without pulmonary arterial hypertension and in a group of healthy control subjects. All subjects underwent cardiac echocardiography and carried out pulmonary function tests. TM patients also filled an IPAQ questionnaire on usual physical activity (PA).Overall, TM patients have a diminished exercise performance in comparison to control subjects. In fact, peak oxygen uptake (V’O2 peak), expressing maximum exercise capacity, was decreased in 81.5% of the patients; similarly, anaerobic threshold (V’O2@AT) and O2 pulse also resulted lowered. In multivariable regression models adjusted for gender, age, BMI, and mean haemoglobin, V’O2 peak and O2 pulse were positively associated with cardiac iron overload (T2*). No ventilatory limitation to exercise was observed. The most important causes of exercise limitation in these patients were muscular deconditioning and reduced cardiac inotropism due to iron deposition. Only 15/54 (27.8%) TM patients used to perform vigorous physical activity. These results suggest that a program of regular physical activity may be useful to increase the tolerance to effort and therefore to improve the quality of life in these patients.

Role of sclrostin (SOST) to predisposing for osteoporosis in β- thalassemia major patients

Sclrostin is a biomarker interrupted in bone resorption process by binding to LRP5 and/or LRP6 family, and prevent Wingless-type signaling (Wnt) which is important to both bone development and the maintain of bone mass. Sixty (60) patients with thalassemia major were enrolled from the period 2/5/2021 to 1/9/2021 in summer to assessment role of sclrostin to predisposing for osteoporosis in β-thalassemia major patients (β-TM). Patients ages were from (2-40 year) males and females they divided to children and adults had osteoporosis and/or osteopenia."All patients diagnosed by Hb electrophoresis and were receiving regular blood transfusions for anemia and chelation therapy for prevention of iron overload related complications. Detailed history and examination including height and weight were recorded on pre-designed questionnaire and blood samples were taken for measurement of serum"sclrostin level. The results showed non-significant differences (P˃0.05) of serum sclerostin (SOST) concentration between osteoporosis of beta thalassemia patients (β-TM) and osteopenia of beta thalassemia patients for both gender, but appeared increased significant (P˃0.05) in male adults of osteopenia with progressive aged.

Evaluation of Corneal and Lens Densitometry with Scheimpflug Imaging in Young Beta Thalassemia Patients

The aim of this study is to compare corneal and lens density of children with Beta (β) thalassemia and healthy controls using Pentacam HR. This is a case-control and cross-sectional study. Anterior segment parameters, corneal, and lens densitometry of patients with β-thalassemia and healthy controls were evaluated with Scheimpflug corneal topography. For corneal densitometry analysis, the 12 mm diameter area of the cornea was divided into four concentric radial zones and anterior, central, and posterior layers according to corneal depth. The mean densitometry value for the crystalline lens was calculated in three regions around the center of the pupil. Non-contact specular microscopy was used to examine the morphology of the corneal endothelium. The study group consisted of 32 β-thalassemia major patients and the control group consisted of 31 healthy volunteers. The mean age of the study group was 12.12±3.94 years (range: 5-19 years) and 10.90±3.84 years (range: 5-19 years) in the control group (P&gt;0.05). Corneal light backscattering in the posterior layer was significantly lower in the patient group than in the control group. Corneal endothelial cell density was determined as 3053.55±189.71 in the patient group and 3214±195.12 in the control group (P=0.094). Lens densitometry values did not differ between the two groups (P&gt;0.05). We detected changes in corneal densitometry examination without any clinical findings in patients with β-thalassemia major. Pentacam may be a suitable screening technique for early detection of β-thalassemia ocular signs in children. Prospective studies with a large number of cases are needed to support these findings.

Molecular characterization of beta globin gene in beta thalassemia patients at Hue Central Hospital

Background: Thalassemia is the most common monogenic disease worldwide. The severity of thalassemia depends on the degree of imbalance between the α-globin and β-globin chains. The aims of the current study were (1) to describe clinical and hematological characteristics of β-thalassemia patients; and (2) to investigate mutations of β-globin gene using Sanger sequencing, as well as the association between β-globin genotype and severity of β-thalassemia. Materials and method: 57 β-thalassemia patients treated at Hue Central Hospital were examined by sequencing the whole β-globin gene. Results: 80.7% with β-thalassemia intermedia, 19.3% with β-thalassemia major. Patients had 100% anemia, 75.4% splenomegaly, 50.9% hepatomegaly, 38.6% thalassemia facies, 28.1% jaundice and 15.8% iron overload; The red blood cell indices were decreased: Hb 7.5 ± 1.3 g/dL, MCV 70.9 ± 8.4 fL, MCH 20.5 ± 2.1 pg. Hemoglobin composition included HbA 35.2 ± 33.9%, HbA2 6.1 ± 2.7%, HbF 24.8 ± 18.0%, and HbE 38.6 ± 15.2%. Nine β-globin gene mutations were observed. The most common genotype was βE/β0, which occupied 80.7%. The βE/βA, β0/βA and βE/β+ genotypes were only found in β-thalassemia intermedia individuals, while the β0/β0 genotype was limited to β-thalassemia major patients. The βE/β0 genotype was seen in both types. Conclusion: There was differences in age of blood transfusion initiation between the genotypes. Among them, the β0/β0 genotype was the most severe. Key words: β-thalassemia intermedia, β-thalassemia major, genotype.

Prevalence of metabolic syndrome in beta-thalassemia major adult patients in Tanta University Hospitals

Introduction: one of long-term complications of Beta-thalassemia major (β-TM) disease is metabolic syndrome, which has a significant influence on patients' quality of life. Objective: to investigate the prevalence of metabolic syndrome in β-thalassemia major patients in Tanta University Hospitals. Materials and methods: our study included two groups. Group I: consist of (100) adult beta-thalassemia major patients. Group II: consist of (100) sex and age matched healthy subjects as control group. Results: the present study revealed that 29% of our β-thalassemia major patients had metabolic syndrome while in control group it was 2.0%, and low high-density lipoprotein (HDL)was the most frequent positive criterion it was 86.0% in β-thalassemia major patients' group. Prevalence of hyperglycemia, abdominal obesity, hypertriglyceridemia, and hypertension in patients with thalassemia was 29, 41, 21and 7%, respectively. Prevalence of metabolic syndrome in female patient was 34.3% while in male beta thalassemia major patient it was 18.2%. the prevalence of metabolic syndrome in well chelated beta thalassemia major patient was 0.0%, while in poorly chelated patients it was 35.4%. Conclusions: this study revealed that 29% of β-thalassemia major group patients had International Diabetes Federation (IDF) criteria of metabolic syndrome and low HDL was the most frequent positive criterion.

Prevalence of metabolic syndrome in beta-thalassemia major adult patients in Tanta University Hospitals

Introduction: one of long-term complications of Beta-thalassemia major (β-TM) disease is metabolic syndrome, which has a significant influence on patients' quality of life. Objective: to investigate the prevalence of metabolic syndrome in β-thalassemia major patients in Tanta University Hospitals. Materials and methods: our study included two groups. Group I: consist of (100) adult beta-thalassemia major patients. Group II: consist of (100) sex and age matched healthy subjects as control group. Results: the present study revealed that 29% of our β-thalassemia major patients had metabolic syndrome while in control group it was 2.0%, and low high-density lipoprotein (HDL)was the most frequent positive criterion it was 86.0% in β-thalassemia major patients' group. Prevalence of hyperglycemia, abdominal obesity, hypertriglyceridemia, and hypertension in patients with thalassemia was 29, 41, 21and 7%, respectively. Prevalence of metabolic syndrome in female patient was 34.3% while in male beta thalassemia major patient it was 18.2%. the prevalence of metabolic syndrome in well chelated beta thalassemia major patient was 0.0%, while in poorly chelated patients it was 35.4%. Conclusions: this study revealed that 29% of β-thalassemia major group patients had International Diabetes Federation (IDF) criteria of metabolic syndrome and low HDL was the most frequent positive criterion.

Effectiveness And Safety Of Direct Acting Antiviral Agents In Thalassaemic Patients With Chronic Hepatitis C.

Pakistan has the highest prevalence of Β-Thalassemia major in children and Chronic Hepatitis C (HCV) infection is a common transfusion transmitted infection. After the emergence of new generations of Antiviral drugs labelled as Direct Acting Antivirals (DAAs), substantial eradication of HCV has been reported as 90-95% with fewer side effects as compared to older regimen of Peginterferon with or without Ribavirin. The main objective of this study was to assess the Rapid virological response (RVR) at 4th week, End of treatment response (ETR) at 12th week and sustained viral response (SVR) at 24th week achieved by using direct acting antiviral and to assess their safety. Retrospective descriptive study was conducted from July 2018 to July 2020 at National Institute of Child Health. All β-thalassemia major paediatric patients with HCV infection and age between 3-14 years were included. Demographic data, liver function test, HCV PCR, and response of antiviral therapy was recorded and analyzed. Safety was determined by adverse effects reported in records and efficacy was documented by clearance of HCV-RNA to see ETR and SVR. Total 21 patients were treated. Mean age was 7.67±3yr and 12 (57%) were male. Mean weight was 19.3±3.2kg. RVR and ETR was achieved in all (100%) and SVR was achieved in 20/21 (95%) patients. Headache in 2(9.5%) and generalized body ache was found in 1 (4.25%) patient. Combined Sofosbuvir and Daclatasvir were found to be effective and safe for treating HCV in Thalassaemia Major Children.

Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia.

Reactivation of γ-globin expression is a promising therapeutic approach for β-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of β-thalassemia: Natural HPFH mutations −113A > G, −114C > T, −117G>A, −175T > C, −195C > G, and −198T > C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from β-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. This study provides evidence of the effectiveness of introducing naturally occurring HPFH mutations as a genetic therapy for β-thalassemia.

Development of a double shmiR lentivirus effectively targeting both BCL11A and ZNF410 for enhanced induction of fetal hemoglobin to treat β-hemoglobinopathies

A promising treatment for β-hemoglobinopathies is the de-repression of γ-globin expression leading to increased fetal hemoglobin(HbF) by targeting BCL11A. Here, we aim to improve a lentivirus vector (LV) containing a single BCL11A shmiR (SS) to further increase γ-globin induction. We engineered a novel LV to express two shmiRs simultaneously targeting BCL11A and the γ-globin repressor ZNF410. Erythroid cells derived from human HSCs transduced with the double shmiR (DS) showed up to a 70% reduction of both BCL11A and ZNF410 proteins. There was a consistent and significant additional 10% increase in HbF compared to targeting BCL11A alone in erythroid cells. Erythrocytes differentiated from SCD HSCs transduced with the DS demonstrated significantly reduced invitro sickling phenotype compared to the SS.Erythrocytes differentiated from transduced HSCs from β-thalassemia major patients demonstrated improved globin chain balance by increased γ-globin with reduced microcytosis. Reconstitution of DS-transduced cells from Berkeley SCD mice was associated with a statistically larger reduction in peripheral blood hemolysis markers compared with the SS vector. Overall, these results indicate that the DS LV targeting BCL11A and ZNF410 can enhance HbF induction for treating β-hemoglobinopathies and could be used as a model to simultaneously and efficiently target multiple gene products.

Health-related quality of life in pediatric patients with β-thalassemia major after hematopoietic stem cell transplantation.

Our main purpose was to evaluate health-related quality of life (HRQOL) in β-thalassemia major patients who underwent transplantation from September 2012 to November 2019. The PedsQL 4.0 scale proxy version was administered to 221 transplant patients aged 5-18 years. Their HRQOL results in the proxy-report were compared with those in the proxy-report of 429 matched healthy peers and 198 matched nontransplant patients. Compared with their healthy peers, the transplant patients exhibited worse HRQOL in the physical health domain (P < 0.001), school domain (P < 0.001) and overall scores (P = 0.006). Patients within 4 years after transplantation exhibited physical functioning (P < 0.001), school functioning (P < 0.001) and overall HRQOL damage (P = 0.001); the scores across all domains for patients more than 4 years after transplantation were not significantly different from those for the healthy controls. The transplant patients rated their HRQOL for all domains better than the nontransplant patients (P < 0.001). The HRQOL of patients after human leukocyte antigen (HLA)-matched related and HLA-matched unrelated donor transplantation were not significantly different. Chronic graft-versus-host disease and two or more comorbidities were independently negatively associated with overall HRQOL outcomes (P = 0.032 and P < 0.001, respectively). In conclusion, patients more than 4 years after transplantation achieve an HRQOL equal to that of their healthy peers.

Left atrial deformation indices in β-thalassemia major patients.

The presence of atrial cardiomyopathy in β-thalassemia major (β-TM) patients complicates their clinical condition. The diagnosis is challenging even with cardiac magnetic resonance (CMR) imaging. Novel echocardiographic techniques are applied to increase the diagnostic yield. Fifty-six β-TM patients and thirty age and sex-matched controls were included in the present cross-sectional study. Heart rate, PR duration, and P axis were measured by electrocardiography, left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD), ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e'), left atrial volume index (LAVI), left atrial strain at reservoir (LASr), conduit (LAScd) and contraction (LASct) phases respectively, left ventricular global longitudinal strain (GLS) by echocardiography, and T2* calculation in patient group by CMR. PR duration, LVEF, LAVI, E/e', GLS, and left atrial deformation parameters differed between patients and controls (p <0.05). In patient group, left atrial strain was correlated with PR duration, LAVI, E/e', GLS, and T2* (p <0.05). T2* was correlated only with left atrial deformation indices (p <0.05). Patients with a history of atrial fibrillation were older, had lower heart rate, prolonged PR, increased E/e' and LAVI, and impaired left atrial strain (p <0.05). LASct differed relative to the presence of atrial fibrillation and myocardial iron overload. Atrial strain could be of clinical use in the early detection of atrial cardiomyopathy. An impaired LASct could identify β-TM patients with undetected episodes of atrial fibrillation. Finally, left atrial strain may be helpful in myocardial iron load estimation.

Hepcidin-to-Ferritin Ratio as an Early Diagnostic Index of Iron Overload in β-Thalassemia Major Patients

Hepcidin (HEPC) hormone production is expected to be elevated in cases accompanying iron overload, but the opposite impact of ineffective erythropoiesis in β-thalassemia major (β-TM) patients overrides this effect. The role of the HEPC-to-ferritin (FER) ratio and its components in iron metabolism along with their diagnostic cutoff values, sensitivity, specificity, and accuracy in β-TM patients with iron overload, were examined in this study. This was a 1:1 case-control study with 120 participants, ages ranging from 2 to 30 years of both sexes, who were assigned into two groups: 60 β-TM patients with iron overload, and a control group, comprising 60 healthy individuals matched by gender and age. In the present study, we found slightly elevated serum HEPC concentration (21.9 ng/mL) compared to the controls (9.9 ng/mL), which was not statistically significant (p =0.1), and the median HEPC-to-FER ratio of the cases was significantly lower than the controls, with the median case-control difference of (–0.366; p < 0.001). Our results revealed a statistically significant impact (p < 0.001) of mean age on the serum HEPC level with the inverse linear correlation of (–0.487, p < 0.001). The area under the curve of the HEPC-to-FER ratio was 0.999 and the optimum cutoff value was 0.046 ng/mL (p < 0.001) with 100.0% sensitivity and 98.3% specificity. In conclusion, we found that serum HEPC-to-FER ratio, with an accuracy of 99.2%, may serve as an excellent index for the diagnosis of iron overload in β-TM patients differentiating them from nonthalassemic controls.

Comparative efficacy, safety, and cost of iron chelation monotherapy vs. combination therapy in pediatric beta-thalassemia major: a single-center retrospective study

Background Iron chelation therapy is used to maintain iron balance in β-thalassemia major patients who undergo repeated blood transfusions.&#x0D; Objective To compare the efficacy, safety, and cost of iron chelation combination regimens [deferiprone (DFP) + deferoxamine (DFO) or DFP + deferasirox (DFX])] vs. high-dose DFP monotherapy (≥ 90 mg/kg/day) in pediatric β-thalassemia major patients.&#x0D; Methods This cross-sectional, retrospective study was done at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Retrospective data was obtained from electronic medical records of pediatric b-thalassemia major patients with serum ferritin of ≥ 2,500 ng/mL and/or transferrin saturation of ≥ 60%, who received either combination or monotherapy iron chelation agents. Outcome effectiveness was determined by the reduction of serum ferritin level of at least 80%. Safety was analyzed descriptively. A pharmacoeconomic analysis was performed based on clinical outcomes consisting of effectiveness and direct medical costs.&#x0D; Results At the end of the study, serum ferritin was reduced in 34.7% of the combination therapy group and 27.5% of the monotherapy group, however there was no significant difference between the two treatments (P=0.391). Nine (19.5%) patients on combination therapy and 17 (21.2%) patients on monotherapy had adverse drug reaction (ADR), with the most frequently reported ADR was elevated transaminase enzyme levels. Cost minimization analysis revealed that monotherapy for 6 months was IDR 13,556,592.64 less expensive than combination therapy (IDR 44,498,732.07); whereas monotherapy for 12 months was IDR 20,162,836.10 less expensive than combination therapy (IDR 78,877,661.12).&#x0D; Conclusion Combination regimens are as effective as monotherapy regimens in reducing serum ferritin in pediatric β-thalassemia major patients. There is no differences of ADR between combination or monotherapy. The average cost per patient is less expensive with monotherapy compared to combination therapy.

Prevalence and risk factors of hepatitis E virus infection among patients with β-thalassemia major in South of Iran

ABSTRACT This study was performed to determine the prevalence and risk factors of hepatitis E virus (HEV) infection among thalassemia patients. All β-thalassemia major patients on regular blood transfusion attending the blood transfusion centers located in southern Iran were invited to participate in this study. ELISA was used to detect anti-HEV IgM and anti-HEV IgG antibodies. The molecular detection of HEV infection was performed by nested RT-PCR assay, targeting the ORF2 region of HEV genome, and sequencing. In this study, 16.67% of thalassemia patients were positive for anti-HEV IgG compared to 12.1% of the controls. Thalassemia patients were negative for anti-HEV IgM and HEV viremia. Patients with blood transfusion every two weeks had significantly higher anti-HEV IgG seroprevalence compared to the patients with blood transfusions at longer intervals (OR: 12.50; 95% CI: 1.76–88.74; P = .012). Anti-HEV IgG seroprevalence was not statistically associated with age, gender distribution, ethnicity, place of residency, education level, and serum levels of liver enzymes. This study reports a high seroprevalence of HEV among thalassemia patients, while frequency of blood transfusion was significantly associated with anti-HEV IgG seropositivity. This suggests that frequent blood transfusion may be a risk factor for exposure to HEV infection among thalassemia patients.

Evaluation of hearing and inner ear functions of beta-thalassemia major patients receiving regular chelation therapy with desferrioxamine

OBJECTIVE: In this study, the hearing functions and inner ear conditions of beta (b)-thalassemia major patients who were treated with desferrioxamine were evaluated. METHODS: This study was conducted with 69 pediatric patients aged seven years and older (Thalassemia group; 42 males, 27 females; mean age 11.0±4.1 year; range, 7 to 15 year), diagnosed with b-thalassemia major, treated with regular iron-chelating agent desferrioxamine for at least three years, and followed in the pediatric hematology and oncology clinic and 67 children (Control group; 36 male, 31 female; mean 12.4±6.8 year; range, 5 to 17 year) without hearing loss and chronic ear disease between January 2017 and January 2020. The patient and control groups were examined by an otolaryngologist. Pure-tone audiometry and distortion product otoacoustic emission tests were performed on the patient and control groups, and the results were compared. RESULTS: No significant difference was found in terms of age and sex in the thalassemia and control groups. In the comparison of hearing thresholds between groups with pure-tone audiometry, the hearing thresholds of the thalassemia group were higher than the control group at a frequency of 8000 Hz in the right and left ears, and the difference was statistically significant. In the comparison of the signal-to-noise ratios between the groups with the distortion product otoacoustic emission test, the decibel values in the right ear at frequencies of 1000 Hz and 6000 Hz were lower in the thalassemia group than in the control group, and the difference was statistically significant. CONCLUSION: In the study, the inner ear functions were found to be affected in patients treated with desferrioxamine. Even if b-thalassemia major patients do not clinically describe hearing loss, we believe their hearing thresholds will increase starting from high frequencies with repetitive desferrioxamine treatment, and they may experience a hearing loss.

The Authority of Gene Modifiers in β-Thalassemia Major and Its Relationship to the Pathophysiology of the Disease

β-Thalassemia, an inherited red blood cell disorder, presents a significant health problem worldwide and is caused by defects in the β-globin gene, resulting in the reduction or absence of β-globin chain synthesis. That leads to blood transfusion dependency with its terrible complications. Polymorphisms at position -158 of XmnI-HBG2 on chromosome 11 and BCL11A site on chromosome 2p16 might be linked with elevated hemoglobin F (HbF) appearance, which may, in turn, improve β-thalassemia sternness. This study aims to walk around the amending effects of XmnI and BCL11A loci on HbF levels in Egyptian β-thalassemia patients. Material and Methods. A prospective case-control study of 70 multi-transfused β-thalassemia major patients and 22 controls was performed in the Paediatric hematology unit of Assiut university hospital from June 2019 till April 2021. PCR-RFLP was used to detect single nucleotide polymorphisms at XmnI and BCL11A site loci. Results. XmnI Polymorphism was detected in 9 of 70 patients and associated with higher mean HbF levels (53.48%) than patients without polymorphism (mean Hb level was 42.23%)(P-Value=0.035). The frequency of CT heterozygous genotype was 8 (11.4%), TT homozygous genotype was (1.4%), while the wild genotype CC was detected in 61 (87.1%) of the cases. While BCL11A Polymorphism detected in 21 of 70 patients did not affect either Hb or HbF levels (P-Value =0.26). The TT genotype frequency was 49 (70%), and TC heterozygous genotype was detected in 21 (30 %) of patients. The CC genotype was absent. Conclusion: XmnI -158Gγ polymorphism, but not BCL11A polymorphism, has a modifying effect on both Hb and HbF levels in Egyptian β-thalassaemia major patients. Our research goal is to investigate the frequency of XmnI and BCL11A polymorphism in thalassemia major and investigate the HbF level difference according to the XmnI and BCL11A polymorphism of phenotype group in thalassemia major.

Prevalence of pulmonary dysfunction in patients with beta thalassemia major: a systematic review and meta-analysis

Background Many studies have been conducted on heart, liver, and endocrine abnormalities in thalassemia; however, studies on pulmonary dysfunction (PD) have been limited. Previous studies on the prevalence of restrictive lung disease (RLD) and obstructive lung disease (OLD) in β-thalassemia major patients have lacked agreement. Objective To assess the prevalence of PD in β-thalassemia major patients by systematic review of the literature and meta-analysis. Methods We searched Cochrane library, PubMed, Web of Science, MEDLINE, Scopus, and Embase for relevant articles. Articles were selected according to the inclusion criteria and data were extracted. The primary outcome was prevalence of pulmonary dysfunction in β-thalassemia major with 95% confidence interval (95%CI). Subgroup analyses were applied to explore the prevalence in different age groups, regions, and serum ferritin levels. Sensitivity analysis and publication bias assessment were also conducted. Results A total of 37 studies comprising 1,467 cases were included in this analysis. Pulmonary dysfunction was present in 64.7% (95%CI 57.6 to 71.1) of cases. The pooled prevalence of RLD (44.9%) was higher than that of OLD (7.6%) and diffusion impairment (DI) (35.6%). Subgroup analysis revealed that the region with the highest pooled prevalence of PD was the Americas (75.2%). The highest prevalence of RLD and DI was found in Asia (48.2% and 44.6%, respectively) and that of OLD in Europe (9.7%). Sensitivity analysis showed that the pooled results were robust. Conclusion A high prevalence of pulmonary dysfunction, mainly RLD rather than OLD, was detected in β-thalassemia major patients.

Occult Hepatitis B Virus Infection among β-Thalassemia Major Patients in Ahvaz City, Iran.

Occult Hepatitis B Infection (OBI) is a critical risk factor for triggering post-transfusion hepatitis (PTH), cirrhosis, hepatocellular carcinoma, and hepatitis B virus (HBV) reactivation, which β-thalassemia major (BTM) patients are at risk of it due to multiple blood transfusions. This study was aimed at determining the prevalence of OBI among BTM patients from Khuzestan Province, Iran. In this cross-sectional study, 90 thalassemia patients, who have received blood 36 to 552 times, participated referred to the Shafa hospital of Ahvaz city from January 2018 to April 2019. ELISA for determining serological markers (HBsAg, anti-HBc, anti-HBs, and anti-HCV) and real-time PCR for detecting HBV-DNA were performed; Nested PCR was conducted for DNA sequencing and determining the genotype of OBI case. Phylogenetic and statistical analyses were done by R package. Of 90 subjects enrolled in this study; 95.5% (86/90) were HBsAg negative, and the frequency of OBI among them was 1.16% (1/86). The anti-HBs, anti-HBc, and anti-HCV were detected in 80.00%, 7.78%, and 12.2% of patients, respectively. HBV-DNA was assessed at four HBsAg-positive subjects as well, and all of them were negative. The phylogenetic analysis showed that the detected HBV DNA in the OBI case belongs to the genotype D. This research, for the first time, demonstrated that OBI is present among β-thalassemia patients in Iran. Also, further studies are necessary to determine the actual prevalence of OBI among BTM patients in Iran to decisions concerning OBI screening, especially in transfusion centers.

Study of uric acid excretion in children with beta-thalassemia major attending Alexandria University Children’s Hospital

Background It is evident that high cell turnover rate is present in patients suffering from β-thalassemia. This is mainly the result of not only chronic hemolysis but also ineffective erythropoiesis. It is thus expected that hyperuricemia will occur. Aim Our study was conducted to study uric acid excretion in β-thalassemia major patients and to determine its relationship to tubular dysfunction in those patients. Patients and methods This case–control study was performed on 60 patients with β-thalassemia major and 15 children who were healthy and well, playing the role of the control group. Thorough history taking, review of medical records, and complete physical examination were done for all patients. Evaluation of uric acid excretion, glomerular and tubular renal functions were performed and compared between patients and the control group. Results Hyperuricemia was found in 48.8% of patients; however, none of the patients had evidence of gouty arthritis or nephrolithiasis. Serum uric acid (SUA) levels in patients who had positive correlation with serum creatinine, urine P/Cr ratio and urine uric acid/glomerular filtration rate (UUA/GFR), negative correlation with eGFR and no correlation with urine calcium/creatinine (UCa/UCr) ratio, blood urea nitrogen (BUN), urine β2 MG, and urinary uric acid/creatinine (UUa/UCr) ratio were assessed. The mean SUA level, BUN, serum creatinine, and levels of eGFR were significantly higher in β-thalassemia patients in comparison to the control group. Urinary P/Cr ratio, urine uric acid/ glomerular filtration rate (UUA/GFR) ratio, β-2 microglobulin levels, UCa/UCr, and UUa/UCr were also higher in β-thalassemia patients in comparison to the control group. The present study has a mean age of 8.62 years for the cases studied, and investigations in patients revealed the following results: mean SUA 5.17 mg/dl, mean BUN 16.58 mg/dl, mean serum creatinine 0.49 mg/dl, mean urine P/Cr ratio 1.40, mean eGFR 141.42 ml/min/1.73 m2, mean UUA/GFR 0.55, mean urine β2 MG 0.18 µg/ml, mean UCa/UCr 0.44, UUa/UCr 1.46, and these results were statistically significantly higher in patients compared with controls. Conclusion Renal dysfunction and hyperuricemia are prevalent among patients with β-thalassemia major, mostly related to hyperfiltration and tubular dysfunction. Early markers of tubular dysfunction (urine β2 MG, UCa/UCr, UUa/UCr) and glomerular dysfunction (urine P/Cr ratio and urinary uric acid/GFR ratio) should be followed up regularly in β-thalassemia major patients.