Beta-globin Chain Research Articles

MiR-30a regulates γ-globin expression in erythoid precursors of intermedia thalassemia through targeting BCL11A

Patients with β-thalassemia suffer from a lack or absence of the beta-globin chain of normal hemoglobin (Hb). Therefore, an increase in fetal Hb (HbF) levels could improve the clinical status of these patients. Downregulation of BCL11A, a key regulatory transcription factor, could ameliorate the clinical status of thalassemic patients by increasing HbF levels. miR-30a expression and its relationship with the BCL11A gene in erythroid precursors was explored in patients with β-thalassemia. The relevance of miR-30a to clinical parameters was also investigated. We evaluated the expressions of miR-30a, BCL11A, and γ-globin genes by quantitative real-time PCR (qRT-PCR) on isolated erythroid precursors from peripheral blood samples of β-thalassemia intermedia (TI) patients and in bone marrow samples from healthy individuals as controls. The correlation between miR-30a expression and clinical indices that included HbF levels, ferritin, and the frequency of blood transfusions were assessed. We observed increased expression of miR-30a in conjunction with decreased BCL11A expression and elevated γ-globin and HbF levels. Patients with elevated miR-30a expression had a higher percentage of HbF and a lower level of ferritin. In addition, we observed that overexpression of miR-30a in erythroid precursor cells led to reduced BCL11A expression and was associated with elevated γ-globin expression. Our findings showed the importance of miR-30a in BCL11A and HbF regulation, and in the clinical status of patients with β-thalassemia.

Hemoglobin hammersmith associated with hemolytic anemia in a 3-year-old Colombian girl

Hemoglobin Hammersmith is a rare unstable variant of hemoglobin with decreased oxygen affinity. We report the case of a 3-year-old Colombian girl that initially consulted due to a presumptive diagnosis of iron deficiency anemia. During the evaluation we noticed typical features of chronic hemolytic anemia such as hepatosplenomegaly, jaundice and indirect hyperbilirubinemia; with the presence of target cells and intraerythrocytic inclusions with appearance of tactoids in the peripheral blood smear. The diagnosis of hemoglobin Hammersmith was confirmed through DNA sequencing revealing a pathogenic heterozygous variant in the beta globin chain gene due to a de novo mutation.

Acute pancreatitis in a child with sickle cell anemia

Sickle cell disease (SCD) is a term used for a group of genetic disorders characterized by production of Hb “S”. Sickle cell hemoglobin opathy occurs due to mutation of beta-globin gene situated on short arm of chromosome 11, where adenine is replaced by thymine in base of DNA coding for the amino acid in the sixth position in beta-globin chain. This leads to an amino acid change in beta chain of Hb molecule, from glutamic acid to valine. The result is profound change in the molecular stability and solubility of Hb “S”. Authors are reporting a 8-year-old girl who is a known case of sickle cell disease presented with complaints of intermittent pain abdomen and vomiting since 30 days. Investigations revealed elevated pancreatic enzymes with radiological evidence of pancreatitis. Packed red blood cell transfusion and appropriate supportive therapy given and child recovered well.

Alterations in Antioxidants and Trace Element with Interleukin 6 Level in β Thalassemia Major Patients

?- Thalassemia major is an inherited blood disorder caused by drop or total absence of beta globin chains. Patients with this blood disorder are repeatedly needed to blood transfusion to survive. There are many experimental and clinical evidence that suggested that the oxidative stress and free radical plays an important role in thalassemia. The aim of the present study was to investigate the level of antioxidant enzymes and trace element with interleukin 6 in ? thalassemia major patients. The blood samples were obtained from 50 patients (30 with ?-thalassemia major and 20 healthy controls).The serum levels of MDA, GSH, Vitamin (E, C), trace element (Fe, Zn, Cu, Se) and antioxidant enzymes (SOD, CAT, GPx) and interleukin 6 were anaslysed using conventional methods. The results showed that the level of MDA, Fe, Cu and interleukin 6 were significantly increased (P<0.05), whereas the activities of GSH, Vitamin (E, C), trace element (Zn, Se) and antioxidant enzymes (CAT, GPx) were decreased significantly (P<0.05) in ?-thalassemia major patients compared with healthy control. This results suggested that the ? thalassemia patients disease activity `and progress could be investigated by determining the oxidative stress marker, trace element and interleukin 6 levels.

Hematological profile of sickle cell disease in Chhattisgarh

Background: Sickle cell disease hemoglobinopathy gets inherited in autosomal recessive pattern. In sickle cell disease substitution of amino acid valine for glutamic acid at the sixth position on beta globin chain takes place resulting in sickled hemoglobin which is a hemoglobin tetramer.Methods: A prospective observational study was conducted in the Sickle Cell Institute, Raipur, India, and Department of Pharmacology in collaboration with Department of Biochemistry, Pt. J.N.M. Medical College, Raipur, Chhattisgarh, India, from February 2018 to June 2018. Patients included were in the steady state for a long period of time without any symptoms related to sickle cell disease or any other diseases which could affect hematological parameters. Subjects transfused in the last three months were excluded. Student t test and Pearson Correlation Coefficient test was done on stat pages and socscistatistics calculators. P-value&lt;0.05 was considered as statistically significant.Results: A total of 50 subjects of sickle cell disease homozygous (SS) were studied for hematological parameters. The mean age±SD of 50 subjects were 13.3±9.24 years. Out of 50 subjects, 35 were males and 15 were females. Total RBC count, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) was low in present study. Significant inverse correlation was found in females between HbA2 and HbF, p=0.01, while it was insignificant and negatively correlated in males being 0.23.Conclusions: Sickle cell disease homozygous is a common and challenging health problem of Chhattisgarh population.

Alpha-hemoglobin-stabilizing protein (AHSP): a modulatory factor in β-thalassemia.

Hemoglobin (Hb) is an iron-containing metalloprotein that transports oxygen molecules from the lungs to the rest of the human body. Among the different variants of Hb, HbA1 is the most common and is composed of two alpha (αHb) and two beta globin chains (βHb) constructing a heterotetrameric protein complex (α2β2). Due to the higher number of AHSP genes, there is a tendency to produce approximately twice as much of α subunit as β subunit. Therefore, there is a chance of presenting excess α subunit leftover in human blood plasma; excess subunits subsequently bind with each other and aggregates β-thalassemia occurs due to lack of or reduced numbers of βHb subunit. Alpha-hemoglobin-stabilizing protein (AHSP) is a scavenger protein which acts as a molecular chaperon by reversibly binding with free αHb forming a complex (AHSP-αHb) that prevents aggregation and precipitation preventing deleterious effects towards developing serious human diseases including β-thalassemia. Clinical severity worsens if mutations in AHSP gene co-occur in patients with β-thalassemia. Considering the mechanism of action of AHSP and its contribution to ameliorating β-thalassemia severity, it could potentially be used as a modulatory agent in the treatment of β-thalassemia.

Prediction of RNA Secondary Structure at IVS1 Mutation of Beta Globin Gene

Background: Beta globin gene is responsible for producing beta globin chains that stabilize the structure and function of hemoglobin. This gene expression is controlled by complex interactions of transcriptions factors and its regulatory elements in a specific manner. Disturbed beta globin genes may result in hemoglobinopathies, mainly sickle cell disease and beta thalassemia. It seems interesting that several mutations occurring in intronic region results in severe symptoms to beta thalassemia patients, such an IVS1nt5 G&gt;C. This research aimed to analyze RNA structural alteration effected by intronic mutation of beta thalassemia. Methods: The most prevalent mutation of beta thalassemia in Indonesia was obtained from Ithanet. The RNA secondary structure of IVS1nt5 G&gt;C and beta globin gen (HBB) wildtype were performed by RNAStructure, along with probknot prediction. Results: The result showed that intronic mutation caused conformational change in beta globin secondary structure, either for max expect or base pairing probability approach. The mutant had bigger and more loops that diminished the protein stability. Thus, the structure might undergo dysfunction. Conclusion: The comprehensive structural-functional significance of these findings needs further study.

Arrhythmias and Sudden Cardiac Death in Beta-Thalassemia Major Patients: Noninvasive Diagnostic Tools and Early Markers.

Beta-thalassemias are a group of inherited, autosomal recessive diseases, characterized by reduced or absent synthesis of beta-globin chains of the hemoglobin tetramer, resulting in variable phenotypes, ranging from clinically asymptomatic individuals to severe anemia. Three main forms have been described: heterozygotes, homozygotes β+, and homozygotes β°. Beta-thalassemia major (β-TM), the most serious form, is characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Cardiac complications represent a leading cause of mortality in β-TM patients, although an important and progressive increase of life expectancy has been demonstrated after the introduction of chelating therapies. Iron overload is the primary factor of cardiac damage resulting in thalassemic cardiomyopathy, in which diastolic dysfunction usually happens before systolic impairment and overt heart failure (HF). Although iron-induced cardiomyopathy is slowly progressive and it usually takes several decades for clinical and laboratory features of cardiac dysfunction to manifest, arrhythmias or sudden death may be present without signs of cardiac disease and only if myocardial siderosis is present. Careful analysis of electrocardiograms and other diagnostic tools may help in early identification of high-risk β-TM patients for arrhythmias and sudden cardiac death.

SPONTANEOUS EPIDURAL BLEED: A DIRE COMPLICATION OF SICKLE CELL CRISIS

SESSION TITLE: Case Report Semifinalists 1 SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Sickle cell disease (SCD) is caused by a single amino acid substitution on the beta globin chain resulting in the propensity of the hemoglobin molecule to polymerize in deoxygenated state. Neurologic manifestation secondary to SCD is common and affects almost 35% of patients. About 54% of these patients suffer from ischemic strokes and 34% from intracranial bleeding. Isolated non-traumatic spontaneous epidural hematoma (EDH) is an exceedingly rare complication of SCD. Other reported etiologies of spontaneous SDH are infectious, coagulation abnormalities associated with end stage renal disease and hemodialysis, dural metastasis and Langerhans cell histiocytosis. CASE PRESENTATION: A 20-year-old African American female with SCD presented with severe generalized pain. She was hypertensive, tachycardic, tachypneic with an oxygen saturation 98% on room air. Physical examination revealed poor bilateral air entry on lung auscultation due to splinting and a normal neurological examination. Blood work showed leukocytosis of 12,800 with 53% neutrophil and 1% band, hemoglobin 7.5 gm/dL, platelet 181,000/dL, reticulocyte count 13%, LDH 1144 IU/L. Liver function tests were normal except a total bilirubin level of 16.2 mg/dL. The patient was started on IV hydration, analgesia was achieved by IV narcotics. About 24 hours after hospital admission, the patient suddenly became unresponsive. An emergent CT scan of the head revealed a large right sided fronto-parietal epidural hematoma with midline shift, subfalcine and uncal herniation. No noticeable bone infarction overlying the hematoma. The patient underwent emergent hematoma evacuation but died 24 hours post-surgery. DISCUSSION: Spontaneous non-traumatic EDH is a rare manifestation of SCD. Only 30 cases have been reported in the literature. The pathophysiology is not completely understood. Three explanations have been proposed over the years. 1) Vaso-occlusion of the haematopoietically active calvarial diploic bone resulting in bone infarction and subsequent leaking of blood in the periosteal and subsequently epidural or in the subgaleal space 2) Acute rapid expansion of hematopoiesis with resultant microfracture of already thinned inner cortex and extravasation of blood and hematopoietic tissue 3) Sludging of sickle cells in the diploic veins hampering venous drainage and oozing of blood due to vascular injury and elevated back pressure.Presence of coagulopathy or platelet dysfunction is also likely responsible for hematoma expansion and worse clinical outcome. Overlying bony infarction is associated with better prognosis. CONCLUSIONS: The understanding regarding this rare disease entity is rapidly evolving in the era of advanced technology and improved awareness among health care providers. We believe this report will shed more light on the clinical as well as the pathophysiologic aspect of the disease process. Reference #1: Hettige S, Sofela A, Bassi S, Chandler C. A review of spontaneous intracranial extradural hematoma in sickle-cell disease. Acta Neurochirurgica. 2015;157(11):2025-9. Reference #2: Ohene-Frempong K, Weiner SJ, Sleeper LA, Miller ST, Embury S, Moohr JW, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood. 1998;91(1):288-94. Reference #3: Banerjee C, Yowtak J, Fridlyand D, Alleyne C, Jr. Acute spontaneous intracranial epidural haematoma and disseminated intravascular coagulation in a paediatric sickle cell patient. BMJ case reports. 2018;2018. DISCLOSURES: No relevant relationships by Hau Chieng, source=Web Response No relevant relationships by Boris Medarov, source=Web Response No relevant relationships by Biplab Kumar Saha, source=Web Response No relevant relationships by Aditi Saha, source=Web Response

PULMONARY HYPERTENSION IN SICKLE CELL DISEASE: LOOKING BEYOND THE USUAL SUSPECT

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Pulmonary hypertension (PH) is common in sickle cell disease (SCD) and is a major risk factor for death with 2-year mortality 40-50%. Autoimmune disease (AID) is an established cause of pulmonary hypertension. Patients with SCD present a defective alternate complement pathway that increases risk of infection and autoimmune diseases. However, coexisting AID and SCD is rarely reported, suggesting possible under-diagnosis due to overlapping symptoms. CASE PRESENTATION: 20 year old male with sickle cell S/O Arab presented with 2 days of hip pain, fever, dyspnea and reproducible, non-exertional chest pain. Admitted for management of acute chest syndrome. He was found to have nephrotic-range proteinuria (protein-creatinine ratio 3.65 mg/mg). Serology markers were positive for ANA titer 1:2560 (speckled pattern), positive RNP (> 8.0) and Smith antibodies (1.9). Echocardiogram revealed right ventricular systolic pressure (RVSP) of 75 mmHg. Patient was diagnosed with mixed connective tissue disease (MCTD) with systemic lupus erythematosus (SLE) predominant features. He underwent kidney biopsy which was consistent with focal segmental and global glomerulosclerosis (FSGS). Right heart catheterization (RHC) showed mean pulmonary artery pressure of 31 mmHg, pulmonary capillary wedge pressure of 5 mmHg, cardiac output/cardiac index 7.95L/min/4.69L/min/m2 respectively, pulmonary vascular resistance of 5.7 Wood units. Patient was initiated on hydroxychloroquine, losartan, and ambrisentan. DISCUSSION: Hemoglobin O Arab is an uncommon hemoglobinopathy due to substitution of lysine for glutamic acid at a position 121 of beta globin chain. Homozygotes are clinically asympatomatic. Compound heterozygous condition in combination with sickle hemoglobin results in Hb S/O Arab , which resembles homozygous sickle cell anemia and manifests with severe hemolytic anemia and recurrent painful crisis (Reference #1). Pulmonary hypertension in SCD is multifactorial, classified as Group V; pre-capillary PH due to hemolysis, impaired nitric oxide bioavailability, asplenia, chronic hypoxemia and thromboembolism; as well as post-capillary PH due to left ventricular dysfunction. Despite the prevalence and negative impact on mortality, there are few data to guide management of PH in SCD. A small number of clinical trials (Walk-PHaSST, ASSET-1 and ASSET-2 trials) failed to prove success with PAH specific therapies, thus it is not recommended for routine use in PH-SCD patients (Reference #2 and #3). Based on RHC data of our patient, he has PAH of combined etiology associated with SCD as well as MCTD with SLE features and therefore we chose to treat him with PAH-targeted therapy. CONCLUSIONS: This case demonstrates importance of increased awareness of coexisting etiologies for PAH leading to a rapid progression and increased morbidity. Reference #1: Hemoglobin S/OARAB: Thirteen New Cases and Review of the Literature. American Journal of Hematology 60:279–284 (1999) Reference #2: Machado RF, Martyr S, Kato GJ, et al. Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension. Br J Haematol. 2005;130:445–453. Reference #3: Br J Haematol. 2010 May;149(3):426-35. https://doi.org/10.1111/j.1365-2141.2010.08097.x. Epub 2010 Feb 17. DISCLOSURES: No relevant relationships by Sandi Khin, source=Web Response No relevant relationships by Ruth Minkin, source=Web Response

3177 Splenomegaly in an Adult Female With Sickle Cell Disease

INTRODUCTION: A mutation in the beta globin chain of hemoglobin results in Sickle type of Red blood cells. To remove the sickle shaped red blood cells, the spleen becomes hyperactive and enlarged. These red cells have more affinity to the vascular endothelial membrane resulting in Vaso-occlusive phenomenon. Repeated episodes of this cause thrombosis, infarction leading to fibrosis and Autosplenectomy. This is generally complete by the age of 5 and for more than 80% in their first decade. Existence of spleen in adolescents and adults with sickle cell disease in uncommon. Here we present such a case. CASE DESCRIPTION/METHODS: A 22-year-old female with known history of homozygous sickle cell disease presents with abdominal pain. She started to have generalized body pains, later localized to all quadrants of the abdomen. She described it as achy type constant pain associated with nausea. She denies any emesis, changes with bowel or bladder habits and association with food intake. CT imaging done revealed an enlarged spleen with scattered densities and a 2 cm splenule in the inferior aspect. The enlarged spleen 14 × 5 × 15 cms was present in prior ultrasound imaging study done 4 years ago. Further laboratory work including complete blood counts with differential, reticulocyte count &amp; index were consistent with sickle cell pain crisis. DISCUSSION: Although the presence of echogenic lesions increases the risk of sequestration crisis, increased Hemoglobin F levels and alpha thalassemia may cause splenomegaly, but the patient did not have either. Hemoglobin Electrophoresis showed Hb F 1% and Hb S of 70%. Some studies conclude splenic enlargement in adulthood may imply less severe form of the disease. With no other possible cause identified, this adult female with Sickle cell HbSS disease has Splenomegaly.

Rare double heterozygosity for poly A(A〉 G) and CD17(A〉 T) of beta thalassemia intermedia in a Chinese family.

Beta thalassemia is a hereditary disorder resulted from mutations in the β globin gene leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. Three types have been defined, based on the degree of reduced beta-globin chain synthesis and clinical phenotype: major, intermedia and minor (heterozygote carrier state). Beta thalassemia intermedia is characterized by heterogeneity for the wide clinical spectrum of various genotypes and a wide range of presentations. The genotypes of beta thalassemia intermedia are much complicated referring to β+/β+,β+/β0, Hb E/β0, β0/β0 compounding alpha thalassemia and so on. In this present case, we reported a rare beta thalassemia intermedia genotype of double heterozygosity for poly A (A〉 G) and CD17(A〉 T) indicated of β+/β0 in a Chinese family.

Erythroferrone Hormone a Novel Biomarker is associated with Anemia and Iron Overload in Beta Thalassemia Patients.

Erythroferrone (ERFE) is a glycoprotein hormone produced by erythroblasts in response to erythropoietic activity by stimulation of erythropoietin that acts directly on the liver to inhibit production of hepcidin, lead to increases iron delivery for intensified activity of erythropoietic. Beta thalassemia are inherited disorders characterized by reduced or absent synthesis of beta globin chains in the hemoglobin (Hb) molecule1 The pathophysiology has been recognized by anemia and iron overload continually with resultant of frequented blood transfusions. We intend to investigate serum ERFE level and their associations with each other. Beta Thalassemia (BT) patients, who were inspected at thalassemia center in ALzahraà hospital teaching period transfusions blood (PTB) for each (14-30 day). Seventy patients were aged about (11-28 year) and 20 subjects healthy as control group, who matched were included in the study. Results. Serum ERFE levels were significantly higher in BT patients compared to control groups. There were significantly (p<0.05) differences in these biomarker between (BTM and BTI), (splenectomy and non splenectomy) groups. a negative correlation between ERFE levels with HB, PCV, MCV, MCH, Iron, and Ferritin while it was a not significant correlated with MCHC and PTB. High level of ERFE as new biomarker in patients with BTM and BTI is associated with mild or severe anemia and iron overload especially in patients with splenectomy.

Hereditary methemoglobinemia caused by Hb M-Hyde Park (Hb M-Akita) (HBB:c.277C > T; p.His93Tyr).

Healthy human blood contains only atrace amount of methemoglobin (HbM), less than 1%. In HbM iron is present in the oxidized ferric state (Fe3+) not in the reduced ferrous form (Fe2+) and this reduces the ability of hemoglobin to bind oxygen. The described rare hemoglobin variant HbM‑Hyde Park (also known as HbM-Akita) results from the substitution of amino acid tyrosine by histidine at position 93of the beta-globin chain of hemoglobin. The rare Hb variant Hb M‑Hyde Park (Hb M‑Akita) is mainly inherited autosomal dominant and causes methemoglobinemia. Due to the low frequency of inherited HbMvariants, the diagnosis is challenging. Here, we here report on afamily with Hb M‑Hyde Park (Hb M‑Akita) whose members demonstrated Hb M > 10%, but were, asymptomatic except for chronic cyanosis. Due to human mobility and migration other hemogobin variants, such as beta-thalassemia minor have spread to Austria . Agenetic combination of two different hemoglobin variants may result in severe anemia. Genetic counseling for patients with hemoglobin variants, including Hb M‑Hyde Park (Hb M‑Akita) and beta-thalassemia minor, is essential.

Assessment of complement regulatory proteins CD35 and CD55 in β-thalassemia patients

BackgroundReduced or absent production of Beta globin chain causing a hemolytic anemia known as beta thalassemia which is an inheritedanemia of variable severity results from imbalances of globin chains, ineffective erythropoiesis and hemolysis. Red Blood cellsare protected from lysis caused by complement via the complement regulatory proteins CD35 and CD55.Aim of the studyTo evaluate CD35 and CD5 in beta thalassemia cases and correlate the serum level of CD35 and CD55 with clinical and hematologicalparameters.Patients and methodsA case control study , included 60 patients who were a known case of β-thalassemia aged between 2_30 years and control groupof 20 participants who were healthy and age and sex matched with case group. All hematological parameters were done by automatedhematological analyzer.Serum level of CD35 and CD55wereestimated in both patients and control subjects by ELISAtechnique.ResultsIn this study, Mean RBC, Hb, PCV, MCH, and MCV were significantly lower in thalassemia cases. Serum level of CD35 wassignificantly lower ,while CD55was significantly higher in patients with thalassemia .There were significant weak positive correlationsbetween CD35and both of RBC and PCV level.ConclusionA low level of CD35 in β thalassemia patients can accelerate the RBC lysis by permitting complement deposition on them.CD35 level showed positive correlation with RBC and PCV and negative correlation with RDW. CD55 is high in thalassemiabut with no significant correlation with any of thalassemic patients’ characteristics.

Multiple endocrinopathies in &amp;beta; thalassemia major child – A case report

Beta thalassemia is a chronic blood disorder characterised by decreased production of beta globin chains and excess accumulation of the other globin chains. Multiple endocrinopathies in β thalassemia major patients are common. Because of iron overload, multiple endocrinopathies are still prevalent despite extensive chelation therapy. Usuallylife expectancy may be increased by regular blood transfusions, butthere might begrowth problems, thyroid dysfunctions, hypoparathyroidism and hypocalcaemia. Here we are presentingaunusual case of various endocrinologicaldys functions in a chronic case of β thalassemia major. Keywords: Hypoparathyroidism, Hypocalcaemia, β-Thalassemia major.

Relative proteome quantification of alpha, beta, gamma and delta globin chains in early eluting peaks of Bio-Rad variant II® CE-HPLC of hemoglobin from healthy and beta-thalassemia subjects in Malaysia

This is the first report of QQQ-mass spectrometric identification and quantification of the Hb subunits, alpha, beta, delta and gamma globin peptides, derived from enzymatic-digestion of proteins in the early unknown peaks of the Bio-Rad cation-exchange chromatography of haemoglobin. The objectives were to assess the relationship of the quantity of the free alpha, beta, delta and gamma globin chains with the phenotypic diversity of beta-thalassaemias (β-thal). The results demonstrate that the pools of free globin chains in red blood cells were correlating with the severity of the disease in patients with different phenotypes of β-thal. The mechanism and the regulation of synthesis of free globin chains pool in a normal individual and in patients with different β-thal phenotypes could arise from several mechanisms which will require further investigation. The role of the free globin pool in patients with β-thal for development of novel therapeutic approaches based on these potential targets requires further investigation. Pertinent biomarkers improves the diagnosis of the β-thal, especially in low-income countries where they are most common and allows more effective therapeutic intervention leading to more successful therapeutic outcome.

The Relationship between Serum Level of Ferritin and Cardiac Troponin T (cTnT) in Children with Major Beta-Thalassemia

Beta-thalassemia is one of the most common inherited blood disorder result from a defect in production of beta globin chain due to mutations in the HBB gene on chromosome 11, range from minor to sever transfusion dependent major beta-thalassemia. Major beta-thalassemia regarded as one of the major health problems in endemic regions as the Mediterranean basin, part of North and West Africa and South East Asia. Frequent blood transfusions cause progressive iron overload and hemochromatosis in the body which is the major complication of treatment lead to accumulation of iron in many organs and meanly in heart. The aim of the study is to determine the relation between serum ferritin and serum cTnT in children with major beta-thalassemia. A cross sectional study was carried out in Kirkuk City from 16th of January 2018 to 15th of March 2018. A total of 60 children with major Beta thalassemia admitted to thalassemia center in Azadi Teaching Hospital, and 30 non major Beta thalassemia children (control group) their age ranged between 2-10 years old, were investigated for s. cTnT and s. ferritin. There was a highly significant increase in s. ferritin level in children with major beta-thalassemia as compare with control of same age and gender. Also, There was a difference between the level of serum cTnT level in children with major beta thalassemia more than control, but not significant of same age and gender.

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.

Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH) Determinations in Newborns with Beta Thalassemia

Newborns with alpha thalassemia trait have microcytic red blood cells (RBCs) used as a diagnostic screening tool at birth. Infants with beta thalassemia present with microcytosis sometime during the first year of life; however, whether microcytosis is present in newborns is unknown. In this study, we determined the MCV and MCH values in newborn infants, who have beta0 thalassemia major, intermedia, and minor by performing a retrospective study, with IRB approval.189 eligible patients seen by the hematology/oncology group of 10 physicians at Children's Hospital Medical Center (CHMC) and UNMC were reviewed. Patients were identified by International Classification Codes-10 (56.1, 56.3, 57.3, 57.4). Of the 189 eligible patients with beta thalassemia major, intermedia, minor, and sickle cell trait (used as controls), there were 28 evaluable and 161 non-evaluable patients. The non-evaluable patients had either the wrong diagnosis (coexisting alpha thalassemia trait) (68) or no laboratory data within the newborn period or up to 6 months of age (93). A second control group used were normal complete blood count (CBC) values by age from the Pathology Laboratory at CHMC. Of the 28 evaluable infants, 5 had beta0 thalassemia major, 2 had sickle-beta+ thalassemia (regarded as intermedia for this study), 7 had beta thalassemia minor, and 14 had sickle cell trait. The diagnosis in each of the 28 infants was confirmed by newborn screening for a hemoglobinopathy and hemoglobin electrophoresis sometime after birth. The MCV, MCH, mean corpuscular hemoglobin concentration (MCHC), hemoglobin (hgb), hematocrit (hct), and red blood cell count (RBC) were taken on evaluable patients within the newborn period through 6 months of age and de-identified using the Safe Harbor Method.MCV and MCH were found to be reduced in newborns with beta0 thalassemia and sickle-beta+ thalassemia. However, infants with beta thalassemia minor had normal MCV and MCH values. The MCHC, RBC, hgb, and hct were comparable to controls and within normal limits. By 3-4 months of age, in the infants with beta thalassemia major or intermedia, the MCV and MCH fell to clinically characteristic levels when compared to controls, and plateaued through 6 months of age. MCV and MCH values for infants with beta thalassemia minor, 0-6 months of age, were incomplete to be able to draw a similar conclusion.The proposed mechanism for microcytosis in major and intermedia is an imbalance between alpha and beta globin chain synthesis, which is not apparent in newborns with minor.In conclusion, the MCV and MCH can be used to screen for beta0 thalassemia major and intermedia in newborns. Although the data are discriminating despite the small numbers, a prospective study should confirm these findings. DisclosuresNo relevant conflicts of interest to declare.