Beta Thalassemia Major Research Articles

Global analysis of erythroid cells redox status reveals the involvement of Prdx1 and Prdx2 in the severity of beta thalassemia.

β-thalassemia is a worldwide distributed monogenic red cell disorder, characterized by an absent or reduced beta globin chain synthesis. The unbalance of alpha-gamma chain and the presence of pathological free iron promote severe oxidative damage, playing crucial a role in erythrocyte hemolysis, exacerbating ineffective erythropoiesis and decreasing the lifespan of red blood cells (RBC). Catalase, glutathione peroxidase and peroxiredoxins act together to protect RBCs from hydrogen peroxide insult. Among them, peroxiredoxins stand out for their overall abundance and reactivity. In RBCs, Prdx2 is the third most abundant protein, although Prdxs 1 and 6 isoforms are also found in lower amounts. Despite the importance of these enzymes, Prdx1 and Prdx2 may have their peroxidase activity inactivated by hyperoxidation at high hydroperoxide concentrations, which also promotes the molecular chaperone activity of these proteins. Some studies have demonstrated the importance of Prdx1 and Prdx2 for the development and maintenance of erythrocytes in hemolytic anemia. Now, we performed a global analysis comparatively evaluating the expression profile of several antioxidant enzymes and their physiological reducing agents in patients with beta thalassemia intermedia (BTI) and healthy individuals. Furthermore, increased levels of ROS were observed not only in RBC, but also in neutrophils and mononuclear cells of BTI patients. The level of transcripts and the protein content of Prx1 were increased in reticulocyte and RBCs of BTI patients and the protein content was also found to be higher when compared to beta thalassemia major (BTM), suggesting that this peroxidase could cooperate with Prx2 in the removal of H2O2. Furthermore, Prdx2 production is highly increased in RBCs of BTM patients that present high amounts of hyperoxidized species. A significant increase in the content of Trx1, Srx1 and Sod1 in RBCs of BTI patients suggested protective roles for these enzymes in BTI patients. Finally, the upregulation of Nrf2 and Keap1 transcription factors found in BTI patients may be involved in the regulation of the antioxidant enzymes analyzed in this work.

Metabolic Profile & Body Composition in Egyptian Children with Transfusion-Dependent Egyptian B-Thalassemia

Background: Metabolic challenges in beta thalassemia major (BTM) carry an additional burden to both chronic anemia and iron overload. Although optimal nutritional support for children with BTM is mandatory, health insurance cover only blood transfusion and chelation therapy. Nutrition support remains subtle for both the family and governmental interest especially in developing countries. Aim: To assess growth, total body composition, lipid and glucose hemostasis in Egyptian children with BTM in relation to iron overload and state of chronic hypoxemia. Subjects and methods: 200 Egyptian children with BTM were recruited, they were 99 females (49.5%) and 101 male (50.5%) and their mean age was 12.15 ± 4.23 years. 50 age- and sex-matched healthy children with same socio-economic background were also enrolled. All of them subjected to history taking; thorough clinical examination, anthropometric measurements (weight, height, mid arm circumference, skin fold thickness and body mass index), body composition analysis (using bioelectric impedance analysis device) and dietetic assessment (using 24-hours dietetic recall). Serum lipid profile (high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol and triglyceride), C-peptide and serum insulin were assessed. Results: Most children with BTM had families with high birth order and nearly half of them had positive family history, in addition consanguinity was reported to be 1.5 times in BTM compared to what was reported in controls. Almost half of the patients were from Cairo, the other half were from the economically less privileged Upper Egypt. Most of patients were diagnosed presented in 1st two years of life at mean age of 1.52 ± 1.66 and 1st transfusion was initiated within first four months after initial diagnosis. Most of patient transfused on low mean pre-transfusion hemoglobin of 8.4± 2.6 g/dl. Most studied BTM had iron overload, median (IQR) of serum ferritin was 1800 (1149 - 3100) ng/ml in the last 2 years, with median (IQR) duration on regular iron chelation was 4 (2-6) years and 12.5% of patients were non-compliant. Children with BTM had a significantly lower nutritional intake (kilocalories, protein, carbohydrate, calcium, and phosphorus) than controls with negative impact on anthropometric parameters and body composition parameters both in pubertal and pre-pubertal stage. There was significant increase in body fat value and percent in female BTM compared to male BTM. While there was significant increase in muscle mass % and body water % in males BTM. Children with BTM had significantly higher triglycerides levels however lower cholesterol, LDL, HDL, insulin and C-peptide compared to control. Factors including age, gender, caloric intake, mean pre-transfusion hemoglobin, transfusion burden, splenectomy, viral hepatitis comorbidity, mean serum ferritin, serum insulin, and HDL have impact on body composition in children with BTM.Conclusion: Poor caloric intake with low pre-transfusion hemoglobin and higher serum ferritin were the main risk factors for poor anthropometric parameters in all ages. Regular assessment of nutrition is crucial for the health of children with thalassemia.Keywords: Thalassemia, Body composition; Nutritional deficiency; Diabetes; Lipid DisclosuresNo relevant conflicts of interest to declare.

Survey of the status of iron and sclerostin in major Thalassemia Patients

Background and Aims: Thalassemia is one the most prevalent genetic anemia in the world; homozygote patients usually suffer from severe disturbances. Osteopenia and osteoporosis are of various types of thalassemia complications which are increase in rate in patients with iron overload conditions. Sclerostin is a protein which enhances bone loss by inhibiting osteoblasts. The aim of this study was to measure sclerostin protein and its association with iron overload in major thalassemia patients. Materials and Methods: Forty patients with major beta-Thalassemia and 40 healthy control individuals were includedin the study; Sclerostin protein and ferritin were evaluated using ELISA method. Results: Mean sclerostin protein was 100.7 pg/ml, in the case group; it was 143.1 pg/ml in the control group.There was a significant differences between sclerostin protein in case and control groups (p= 0.015). The association of sclerostin and ferritin was not significant in the case group (p= 0.7), while it was meaningful in the control individuals (p= 0.037). Conclusion: Our findings suggest that sclerostin protein can play an important role in the pathogenesis of osteoporosis.

Thyroid Function in Chronically Transfused Children with Beta Thalassemia Major: A Cross-Sectional Hospital Based Study.

Background Thalassemia is the most common genetic disorder worldwide. Use of iron chelators has improved survival but endocrine complications have become more frequent. The frequency of hypothyroidism in Beta Thalassemia Major (BTM) children ranges from 6 to 30 %. Thyroid dysfunction mainly occurs by gland infiltration, chronic tissue hypoxia, free radical injury, and organ siderosis. Objectives (a) To evaluate the thyroid function status in chronically transfused children with BTM, in the first and second decade of life and (b) to study the influence of factors like duration and amount of blood transfusions, serum ferritin level, and iron chelation therapy on thyroid function. Methodology BTM children, 3 years old and above, on regular blood transfusions with serum ferritin > 1500 mcg/l were included in the study. Thyroid function and ferritin assessment was done using ELISA kits. Autoimmune thyroiditis was ruled out by antithyroid peroxidase and antithyroglobulin antibody testing. Results A study population of 83 children consisted of 49 boys (59%) and 34 girls (41%). 4.8% of the children had evidence of subclinical hypothyroidism. Among them two belonged to the first decade and the other two to the second decade of life. Mean TSH, FT4, and ferritin values among children with thyroid dysfunction were 6.38 ± 0.83 mIU/ml, 1.08 ± 0.45 ng/dl, and 3983.0±1698.30 ng/ml, respectively. The severity of thyroid dysfunction was statistically significantly associated with higher serum TSH values in children in the second decade of life with a p value = 0.001. No other significant correlation was found between oral chelation, amount and duration of blood transfusion, or serum ferritin levels. Conclusion Subclinical hypothyroidism was the thyroid dysfunction observed in our study. Regular blood transfusions with adequate chelation may decrease incidence of thyroid dysfunction.

Health-related quality of life (HRQoL) in beta-thalassemia major (β-TM) patients assessed by 36-item short form health survey (SF-36): a meta-analysis.

The main purpose of this meta-analysis was to evaluate the impact of beta-thalassemia major (BTM) on the health-related quality of life as assessed by the medical outcomes short-form-36 questionnaire (SF-36). A systematic literature search was performed on Cochrane library, Web of Science, Scopus, Science Direct, ProQues, Medline/PubMed, Scholar Google until March 17, 2017 to obtain eligible studies. A fixed effect model was applied to summarize the scores of each domain. The radar chart was used to compare the scores of BTM patients with other health conditions. Spearman's correlation analysis and meta-regression were used to explore the related factors. 26 studies were included in this study, which were all reliable to summarize the scores of the SF36. Pooled mean scores of the physical health domains ranged from 52.74 to 74.5, with the GH and PF domains being the lowest and the highest, respectively. Further, the pooled mean scores of the mental health domains varied between 59.6 and 71.11, with the (MH-VT) and SF domains being the maximum and the minimum, respectively. Patients with BTM had a substantially compromised HRQoL in comparison with the general population. BTM could adversely affect the HRQoL of patients. Measuring HRQoL should be considered as an essential part of the overall assessment of health status of BTM patients, which would provide valuable clues for improving the management of disease and making decisions on the treatment.

EVALUATION OF HEARING IN PATIENTS WITH BETA THALASSEMIA MAJOR

EVALUATION OF HEARING IN PATIENTS WITH BETA THALASSEMIA MAJOR Ahmed Fadhil Hasan*, Husam Haider Salman# & Jaafar Muhsen Khalaf@ *MB, ChB, FICMS, CABS ENT HNS, ENT Senior Surgeon at Al Shafaa General Hospital. #FRCS, DLO. Retired, Department Of Surgery, College Of Medicine, Basrah University. @MB,ChB, FICMS ENT, ENT Surgeon, Basrah Teaching Hospital, Basrah, IRAQ. Abstract This prospective study was conducted in Basrah Teaching Hospital to evaluate the hearing of β thalassemia major patients, and to find the association between desferoxamine (DFO) therapy and hearing loss (HL). Pure tone eudiometry (PTA) and tympanometry was done to determine hearing thresholds of (23) β thalassemia major patients and (50) non thalassemic subjects. All subjects were more than 4 year old to allow PTA to be done. The criteria of evaluation included a full otological history, drug history, otological examination, audiological evaluation using PTA and tympanometry. This study found that (6) out of (23) thalassemic patients and (6) out of (50) non thalassemic patients have hearing loss. From those thalassemic patients with HL, (5) patients have conductive hearing loss (CHL) and one have sensorineural hearing loss (SNHL), while the non thalassemic patients with HL all have CHL, also we found that (3) out of (5) thalassemic patients not on desferoxamine therapy have HL. In conclusion, β thalassaemia major has no significant statistical association with hearing problems, and there is no significant statistical association between desferoxamine therapy and hearing loss.

Features and determinants of hypothyroidism in patients with major beta thalassemia from Algeria.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Biological and endocrine features of Infra Clinical Hypoparathyroidism in Major Beta Thalassemia at adulthood in Algeria, screening and therapeutic management

Biological and endocrine features of Infra Clinical Hypoparathyroidism in Major Beta Thalassemia at adulthood in Algeria, screening and therapeutic management

Fcγ receptor III expression and morphological maturity on neutrophil are associated with higher iron level of major beta-thalassemia

Lifetime blood transfusion experienced by major β-thalassemia patients complicated with iron overload, therefore, may lead to their tissue injury. Ultimately, free toxic iron may alter immune response via dysregulation of immune cell activity producing prolonged effector reaction. Neutrophil as one of the vital innate immune cell despite serves as the first line of defense resulting acute inflammation has a pivotal role in chronic inflammation while releasing the toxic substance that interferes biological processes. This process is initiated by one of them by activation of Fcγ Receptor III (CD16), a neutrophil membrane-bound protein. A cross-sectional laboratory study involving lysed-erythrocyte heparinized whole blood of fifty pediatric major β-thalassemia patients treated with monoclonal antibodies i.e. CD16, CD14, and HLA-DR, dissected into CD16+ and CD16++ population using flow cytometry. Expression of Fcγ Receptor III was measured as Median Fluorescent Intensity (MFI). Hematology and iron status were measured. A correlation analysis was done. MFI of CD16 neutrophil [509.5 (371 - 796.5)] and ferritin level [(3209 µg/L, 1862 - 4564)] was positively correlated (r = 0.4, P = 0.007). Respectively, ferritin and serum iron were found negatively correlated with segmented neutrophils (r = -0.3, P = 0.02; r = -0.3, P = 0.02). Change in CD16 expression may implicate preliminarily neutrophil activation as a response of iron-overloaded tissue and result in chronic inflammation in β-thalassemia patients. However, the maturity of this cell may be altered. Future study in the understanding of neutrophil-mediated inflammation, particularly related to immune complexes and functionality, is imperative to be explored.

Impaired acylcarnitine profile in transfusion-dependent beta-thalassemia major patients in Bangladesh

Patients with beta-thalassemia major (BTM) suffer from fatigue, poor physical fitness, muscle weakness, lethargy, and cardiac complications which are related to an energy crisis. Carnitine and acylcarnitine derivatives play important roles in fatty acid oxidation, and deregulation of carnitine and acylcarnitine metabolism may lead to an energy crisis. The present study aimed to investigate carnitine and acylcarnitine metabolites to gain an insight into the pathophysiology of BTM. Dried blood spots of 45 patients with BTM and 96 age-matched healthy controls were analyzed for free carnitine and 24 acylcarnitines by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although medium chain acylcarnitine levels were similar in the patients with BTM and healthy controls, free carnitine, short chain acylcarnitines, long chain acylcarnitines, and total acylcarnitine levels were significantly lower in patients with BTM than in the healthy controls (P < 0.05). Moreover, an impaired fatty acid oxidation rate was observed in the patients with BTM, as manifested by decreased fatty acid oxidation indicator ratios, namely C2/C0 and (C2 + C3)/C0. Furthermore, an increase in the C0/(C16 + C18) ratio indicated reduced carnitine palmitoyltransferase-1 (CPT-1) activity in the patients with BTM compared with that in the healthy controls. Thus, a low level of free carnitine and acylcarnitines together with impaired CPT-1 activity contribute to energy crisis-related complications in the patients with BTM.

The Correlation between Ferritin Levels and Glutation (GSH) Levels in Major Beta Thalassemia Patient at dr. Soebandi Jember Hospital

Repeated blood transfusions in patient with Major Beta Thalassemia leads to iron overload marks by the increased of serum ferritin levels. Free iron caused the change of H2O2 to oxidants by fenton reaction and caused oxidative stress. These oxidants will be counteracted by GSH as antioxidants. The purpose of this study was to investigate the correlation between ferritin levels with GSH in patients with major beta thalassemia in RSD dr. Soebandi hospital Jember. The samples of this study are fifteen (15) patients age 1-18 years who were regularly transfused. Serum ferritin levels were measured by Enzyme-Linked Fluorescent Immuno Assay (ELFA) and plasma GSH levels were measured by Ellman method. Data was analyzed using Pearson correlation test. Serum feritin levels were increased in Major Beta Thalassemia children with average of 3540,46 ± 3925,37 ng/mL. The mean of GSH is 10,46 ± 2,58 µmol. We found significant and negative correlation between serum ferritin and GSH with p value=0,000 and r=-0,951 in Major beta thalassemia patient at RSD dr. Soebandi Jember.&#x0D; Keywords: Thalassemia, Oxidative stress, Feritin, GSH

The Correlation of Cardiac and Hepatic Hemosiderosis as Measured by T2*MRI Technique with Ferritin Levels and Hemochromatosis Gene Mutations in Iranian Patients with Beta Thalassemia Major.

Organ-specific hemosiderosis and iron overload complications are more serious and more frequent in some patients with beta thalassemia major (BTM) compared with others. We investigated whether coinheritance of HFE H63D or C282Y gene mutations in patients with BTM contributes to the phenotypic variation of iron overload complications and assessed the correlation of cardiac and hepatic hemosiderosis with plasma ferritin levels. We studied 60 patients with BTM with a mean age of 17.5±9.1 years from the Northwest of Iran. HFE gene mutations were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Cardiac and hepatic hemosiderosis was assessed using T2*magnetic resonance imaging (MRI). Ferritin levels were measured using the enzyme immunoassay method. Ferritin levels showed a strong inverse correlation with hepatic T2*MRI values (r = -0.631, p = 0.001) but a poor correlation with cardiac T2*MRI values (r = -0.297, p = 0.044). The correlation between cardiac T2*MRI values and hepatic T2*MRI values was poor and insignificant (r = 0.287, p = 0.058). Genotype and allele distribution of HFE H63D and C282Y mutation did not differ significantly between patients with and without hepatic or cardiac hemosiderosis (p > 0.050). However, carriers of HFE 63D allele had significantly higher ferritin levels compared with non-carriers (1 903±993 vs. 992±683, p < 0.001). Cardiac T2*MRI values showed a poor correlation with hepatic T2*MRI values and ferritin levels. Accurate assessment of cardiac iron overload in patients with BTM can only be done using the T2*MRI technique. Additionally, HFE H63D is a significant determinant factor for elevated ferritin levels in BTM patients.

A pilot study on sperm DNA damage in β-thalassemia major: is there a role for antioxidants?

Excess iron deposition in patients with beta thalassemia major (BTM) causes excess free radical formation, damages the hypothalamic pituitary testicular axis and production of sperms with DNA defects. As antioxidants were reported to improve fertility in healthy males; their effectiveness to improve sperm DNA defects in adult males with BTM was studied. Twenty fully pubertal BTM patients were included consecutively, all had semen analysis; 10 were found to be azoospermic, so further analysis for sperms and DNA defects was conducted on the remaining 10 participants. Semen was analyzed for antioxidants in seminal plasma and sperms for defects including the DNA fragmentation index, sperm deformity index, teratozospermia index and acrosomal index. Participants were then given L-carnitine and N-acetylcysteine for 6 months. All semen parameters were reassessed after treatment. The sperm deformity index and teratozospermia index increased significantly after treatment from 1.90±0.33 to 2.46±0.61 and from 1.59±0.22 to 1.86±0.28 respectively. So, apparently antioxidants accentuated sperm deformities in men with BTM. Therefore, the results of this study are not in favour with the use of antioxidants in BTM patients for improving potential fertility. Larger studies, however, are needed to confirm these preliminary results. (www.actabiomedica.it)

Evaluation of protein Z plasma level in beta-thalassemia major patients in Ahvaz city in Iran

Thrombotic episodes occurred frequently in beta-thalassemia major (BTM) patients, leading to hypercoagulability of plasma. Protein Z (PZ) is a vitamin-K-dependent anti-coagulation factor that plays a role in the human homeostatic process. The objective of the current study is to investigate the distribution pattern of PZ plasma concentrations between BTM patients and the normal population in Ahvaz city, the center of Khuzestan province, southwest of Iran. Forty confirmed BTM patients and 40 healthy volunteers were evaluated for complete blood count (CBC) indices and PZ plasma levels. CBC samples were measured using an automated cell counter, and PZ was assayed with an immunoassay method. Statistical analysis was conducted using SPSS software. The ROC curve and binary logistic regression estimated the sensitivity, specificity, and Odd’s ratio for PZ measurement. The mean±SD of the PZ plasma level in normal individuals was 1.68±0.63 μg/mL, and in BTM patients, it was 1.10±0.52 μg/mL. This shows a significant reduction of PZ in BTM patients statistically (CI = 0.99; p<0.001). Further, the mean±SD of the PZ plasma levels in BTM patients who received washed red blood cells was not significantly different from that of patients undergoing packed red blood cell therapy (CI = 0.95; p = 0.320). The area under the curve (AUC) for PZ was 0.759 (p = 0.00). The cut-off value = 1.4 μg/mL of the PZ plasma level had at least 70% sensitivity and specificity in BTM patients. Several epidemiologic studies have shown thromboembolism episodes in BTM patients. In the current study, PZ was reduced significantly in BTMs. We noticed that BTMs have lower plasma PZ concentration might be predisposed to BTM.

Thalassemia Spectrum and Prenatal Diagnosis among Voluntary Couples in Shushtar City, during a Five Year Period

Background: Thalassemia and other hemoglobinopathies are inherited disorders that result from genetic defects causing deficient synthesis of hemoglobin polypeptide chains. This study was done to determine the prevalence and to study the complete spectrum of alpha and beta thalassemia gene mutations in the voluntary hemoglobinopathy carrier couples-to-be referred to health centers of Shoushtar city, located in the north Khuzestan province. Methods: Subjects referred to health centers of the city of Shoushtar during 2011 - 2016 were evaluated for the presence of thalassemia minor. After that, alpha and beta thalassemia gene mutations were explored in suspected couples. The samples that underwent PND and diagnosing of causative mutational genes by chorionic villus sampling (CVS) through amniocentesis plus direct or indirect genetic testing at first trimester of pregnancy were proved to be a carrier for alpha thalassemia, beta thalassemia, or other hemoglobinapathies. Results: The mutations for 111/165 (67%) of beta thalassemia chromosomes (19 different mutations) were identified. Of which, IVSII-1 (G > A) and CD 36 - 37 (-T) mutations showed the highest frequency (23.4 for each one) followed by IVSI-110 (G > A) (10%), CD 82-83 (-G) (9%), and -110 (C > T) (7.2%). Among the alpha thalassemia subjects (54/165 (33%)), the -α3.7 mutation was the most common (79/6%) determinant identified in the city of Shoushtar. From 48 voluntary carrier couples who underwent PND, 10 (20.8%) couples were proved to have fetuses with major beta thalassemia; pregnancy termination was done for them. Conclusions: These data suggest that the spectrum of mutations in the city of Shoushtar differs from those reported from other parts of Iran. Therefore, in order to save the time and cost, it is recommended that for the prenatal diagnosis of thalassemia in the city of Shoushtar, analysis of common mutations should be considered as a front line screening strategy. Prenatal diagnosing in this survey demonstrated that beta thalassemia was the most common accounting for all disorders.

Evaluation of Dento-maxillofacial Changes in Pediatric ß-Thalassemia Major Patients in Northern Iran

Background Thalassemia is a group of congenital disorders which is characterized by a deficient synthesis of alfa or beta globulin chains in hemoglobin molecules. Due to the problems resulting from changes in face, especially in dento-maxillary regions, such patients require special attention regarding oral health. Thus in this study, we aimed to assess the dento-maxillofacial changes in Beta-thalassemia major (BTM) children and Adolescent patients in Northern Iran. Methods BTM subjects aged 2-15 years and their systemically healthy controls were evaluated in this case-control study. Dento-maxillary changes (spacing, crowding, Posterior cross bite, open bite, deep bite, overjet), dental occlusion, and facial changes (maxillary protrusion, malar prominence, saddle nose and frontal bossing), were evaluated. Data was analyzed SPSS version 22.0. Results There were 66 BTM patients and 66 healthy controls in this study, including 40.9% male and 59.1% females. The average age was 12 ±3.31years. Open bite (P 0.05). Conclusion With regarding to high prevalence of facial changes of BTM patients (57.6 %), preventive care, education and early dento-maxillofacial evaluation and management is advised.

Premature atherosclerosis in children with beta-thalassemia major: New diagnostic marker

BackgroundEarly vascular alteration, atherosclerosis and coronary artery disease have emerged as important cardiovascular complications among beta-thalassemia major (B-TM) patients. The aims of the current study were to assess the prevalence of premature atherosclerosis among our B-TM patients, and to investigate the diagnostic value of serum Osteoprotegerin assay as an early biomarker for atherosclerosis.MethodsThis cross-sectional study was conducted at Hematology unit - Pediatric Department, Zagazig University Children Hospital- Egypt in the period from March 2014 to March 2015. A total of 115 children were enrolled in the current study; as sixty-five (65) children with beta thalassemia major aged 5–18 years, on regular blood transfusion regimen represented the patient group. While fifty (50) healthy children, with comparable age and gender, were assigned as control group. All participants were subjected to history taking, thorough clinical examination and laboratory investigations including; complete blood count, liver and kidney function tests, C- reactive protein, lipid profile, serum ferritin and serum Osteoprotegerin (OPG) assay. Also, carotid artery intima media thickness (CAIMT) was performed by duplex ultrasound for patients and controls.ResultsOur B-TM patients were transfusion-dependent for as long as 8.5 ± 3.8 years with significantly higher serum ferritin levels (2490 ± 1579 ng/dl vs 83 ± 32 ng/dl, p = 0.001), C-reactive protein (5.7 ± 5.7 vs 0.9 ± 0.9), liver enzymes and bilirubin when compared to controls. Significantly higher serum triglyceride (128 ± 20 vs 101 ± 7 mg/dL, p = 0.009) and atherogenic index of plasma (0.45 ± 0.12 vs 0.22 ± 0.04, p = 0.001) were recorded in patients than comparisons. On the contrary, total serum cholesterol (116 ± 16 vs 143 ± 5, p < 0.001), low density lipoprotein-cholesterol (LDL-C) (44 ± 9 vs 73 ± 6, p < 0.001) and high density lipoprotein cholesterol (HDL-C) (39 ± 2 vs 61 ± 5, p < 0.001), were significantly lowered in patients versus normal peers. Carotid arteries intima media thickness (CAIMT) of both side were significantly increased for patients (Rt 0.62 ± 0.2 vs. 0.29 ± 0.07 mm, p = 0.001 & Lt 0.66 ± 0.17 vs 0.29 ± 0.05 mm, p = 0.001) when compared with healthy controls, and showed positive correlation with, serum triglyceride, atherogenic index of plasma, and serum Osteoprotegerin levels. ELISA assay of serum Osteoprotegerin (OPG) revealed significantly higher levels for thalassemia patients than matched healthy controls (427 ± 102 vs. 324 ± 126 pg/ml, p = 0.02). Of particular interest is the obvious positive correlation between OPG levels and CAIMT of both sides (Rt r 0.54, p = 0.001 &Lt r 0.479, p = 0.001) and also with serum triglycerides (r 0.374, p = 0.03).ConclusionsSubclinical atherosclerosis started prematurely in children with beta- thalassemia. Carotid artery intima media thickness represented a simple, accurate and non-invasivemodality for early detection ofatherosclerosis. It was correlated well with serum Osteoprotegerin; this finding highlighted the possible validity of OPG assay as an early predictor of atherosclerosis in thalassemia children.

The Effects of HFE Polymorphisms on Biochemical Parameters of Iron Status in Arab Beta-Thalassemia Patients.

In this study, the potential effect of three HFE gene polymorphisms (C282Y, H63D and S65C) and the SLC40A1 A77D polymorphism on iron balance was investigated in 234 subjects (91 Arab beta-thalassemia major (BTM) patients, 34 beta-thalassemia trait (BTT) individuals and 109 health controls). Genotyping was done using restriction-fragment-length polymorphism and direct-sequencing. Serum-iron, total iron binding capacity, transferrin and ferritin were estimated in all BTT and BTM, and in 65 healthy controls. H63D was the only polymorphism detected in our cohort. Allele frequency was 13% in both BTM and BTT and 10% in controls with no significant difference. Serum iron, ferritin and transferrin saturation were significantly higher in normal males heterozygous for H63D as compared to homozygous wild-type males. Ferritin was significantly higher in BTT males with or without H63D polymorphism when compared to the healthy males with H/H genotype. No such difference was observed between H/H versus H/D BTT subgroups. We conclude that H63D is the only significant hemochromatosis-associated polymorphism in the Arabian Gulf region. The heterozygous state of H63D may significantly alter iron parameters in normal males. In BTT, it appears that the beta-thalassemia allele has an overriding influence on ferritin values, and this generally manifest in males.

Total Antioxidant Capacity in beta-thalassemia: A systematic review and meta-analysis of case-control studies.

Total Antioxidant Capacity (TAC), a biomarker measuring the antioxidant potential of body fluids, including redox synergistic interactions, is influenced by the presence of products of catabolism such as bilirubin (BR) and uric acid (UA). Hyperuricaemia and increased BR levels were observed in thalassemia. In order to evaluate the differences in TAC values between thalassemic patients and healthy subjects, we performed a systematic review and meta-analysis of case-control studies. After the exclusion of data deemed unsuitable for meta-analysis inclusion and a study imputed of bias by Trim-and-fill analysis, mean difference (MD) and confidence intervals 95% (CI 95%) were calculated by the random effect model for beta-thalassemia major (BTM) (1351 subjects: 770 thalassemic and 581 controls, from 15 studies) and Trait (BTT) or Hemoglobin E (BTE) (475 subjects: 165 thalassemic and 310 controls, from 5 studies). Despite the differences in clinical symptoms and severity, similar decreased levels of TAC were found in BTM [MD -0.22 (-0.35 -0.09) p<0.001] and BTT or BTE [MD -0.22 (-0.44 -0.01) p<0.05]. In conclusion, UA and BR interference on TAC suggests that corrected TAC and in particular the UA-independent TAC, considering the prominent influence of UA, might be the better approach to evaluate body antioxidant status.

Effects of Packed Red Cell Transfusion on Blood Glucose Concentrations in Beta Thalassemia Major (BTM) Ashort Presentations of Personal Experience

The most accurate method with which to evaluate altered glucose metabolism in patients with TM is still controversial. Even if the annual oral glucose tolerance test (OGTT) by the age of 10 years is the recommended method, a diagnosis of ’normal’ glucose tolerance during OGTT does not exclude abnormal postprandial glucose levels at home . There is now evidence that the OGTT method, evaluating fasting and 2-h post load glucose, may miss episodes of hyperglycaemia . Furthermore, the credibility of Hb A1c has been questioned because the hemoglobin composition of patients’ erythrocytes are considerably modified, due to regular and frequent transfusions. The results may be falsely increased or decreased depending on the proximity to transfusion, shortened erythrocyte lifespan and the assay used . It has been demonstrated recently that the continuous glucose monitoring system (CGMS) is a useful and valid tool in defining glucose metabolism in children and adults affected by TM with early glucose derangements . Indeed, the CGMS allows monitoring of glycaemic profiles throughout a period of 72 h for a total of 288 glycaemic registrations per day. It identifies glycaemic excursions and constitutes a valid device to understand the 24-h glycaemic trend and profiles. Rimondiet al. investigated the value of using CGMS in six TM patients with abnormal glucose homeostasis after an oral glucose tolerance test (OGTT) . Two-hour OGTT glucose values and CGMS fluctuations were classified as normal if < 7.8 mmol/l, impaired if 7.8 to 11.1 mmol/l, diabetic if > 11.1 mmol/l. The TM patients spent from 1 to 23% of the time with a blood glucose level from 7.8 to 11.1 mmol/l. we evaluate three patients with Beta Thalassemai major using CGMSPatient 1 A 15 year old male with TM presented with nocturia. His FBG was 5.6 mmol/L and OGTT showed a BG level at 2hrs of 8.5 mmol/l. His CGMS showed a diabetic range of BG after dinner and overnight. Based on this tracing, a basal insulin (Glargine) was prescribed at night. A satisfactory response was recorded by CGMS .Patient 2 A 14 year old girl with TM with no symptoms related to glycemic abnormalities. Her FBG was 4.9 mmol/L and an OGTT showed a BG level at 2 hrs of 6.9 mmol/L (IGT). CGMS tracing showed prolonged persistent hyperglycemia after lunch suggesting a need for prandial insulin to cover her carbohydrate load. Insulin aspart before lunch properly controlled her glycemia . Patient 3 A 13 year old boy with TM had a normal FBG (4.5 mmol/L) and OGTT (2h BG =7.6 mmo/l). Applying CGMS monitoring showed IGT state. Furthermore, the effect of packed red cell transfusion showed marked reduction of his BG before meals and overnight. This is the first case to document the rapid beneficial effect of blood transfusion on glycemia in patiens with Beta thalssemia Major Advances in TM care have led to improved survival and quality of life in patients with TM; however, many chronic endocrine diseases have emerged as a result of potential endocrine complications by routine screening and a high index of suspicion is imperative for patients with TM to receive timely treatment.Our results demonstrate that the CGMS is a useful method to detect the variability of glucose fluctuations and offers the opportunity for better assessment of glucose homeostasis in TM patients. Proper and early iron chelation or the use of intensive iron chelation in those with high iron load the new oral chelators have been shown to decrease or reversethese glycemic abnormalities.In addition, optimization of insulin therapy with the help of CGMS appears to be clinically useful and costeffective approach. DisclosuresNo relevant conflicts of interest to declare.