scholarly journals Genetic Mutation of Hb E/beta Thalassemia Patient in Bangladesh and Its Relation With Clinical Severity

2021 ◽  
Author(s):  
Nishat Mahzabin ◽  
Md. Abdul Aziz ◽  
Md. Akhlak-Ul Islam ◽  
Nusrat Jahan ◽  
Md. Kamrul Hasan Sajib ◽  
...  
Keyword(s):  
High Performance ◽  
Mutational Analysis ◽  
Severe Disease ◽  
Genetic Mutation ◽  
Clinical Severity ◽  
Beta Thalassemia ◽  
Thalassemia Patient ◽  
Cross Sectional ◽  
Hemoglobin E ◽  
Hb E

Abstract Background: Hemoglobin E/β-thalassemia is a common inherited hemoglobin disorder among South Asian countries. The phenotypically diverse presentation of the disease is often attributed to coinheritance of β-globin (HBB) gene mutations. The current study described the phenotype and genetic basis of Hb E/β-thalassemia patients and assessed its relation with clinical severity.Methods: A total of 32 patients were included in this cross-sectional study. Cases were confirmed by using capillary hemoglobin electrophoresis or high-performance liquid chromatography. Those with positive findings were further analyzed with clinical information and ancestral data either from the interview or medical records. Data collection was confined to May 2019 and July 2020. Gene sequencing was performed using Sanger’s sequencing method for mutational analysis, and Mahidol scoring was used to grade clinical severity.Result: A total of 13 heterozygous mutations were identified in the HBB gene. Of all, IVS-1-5 (G>C) (n=17, 53.1%) was the most common, and codon 30 (G>C) (n=4, 12.5%) was the second most common mutations. According to the Mahidol scoring system, 37.5% (n=12) were classified as phenotypically mild, 43.8% (n=14) as moderate and 18.8% (n=6) as severe. The IVS-1-5(G>C) mutation was found to be frequently associated with severe disease and showed no mild form.Conclusion: The present study described the clinical severity and its association with genetic mutations in hemoglobin E/β-thalassemia patients. This finding could guide individually tailored management strategies for this particular group of patients.

Spectrum of Genetic Mutation in Beta Globin Gene in Various Type of Thalassaemia in Bangladesh

2021 ◽  
Vol 5 (02) ◽  
pp. 57-60
Author(s):  
Nishat Mahzabin ◽  
Md. Akhlak-Ul- Islam ◽  
Kazi Mohammad Kamrul Islam ◽  
Khaza Amirul Islam ◽  
Md. Arif-Ur- Rahman ◽  
...  
Keyword(s):  
Globin Gene ◽  
Phenotypic Expression ◽  
Gene Mutations ◽  
Cross Sectional Study ◽  
Genetic Mutation ◽  
Compound Heterozygous ◽  
Cross Sectional ◽  
Beta Thalassaemia ◽  
Hb E ◽  
Beta Gene

Background: Hb-E/Beta thalassaemia is a congenital haemoglobin disorder which is a compound heterozygous state consists of qualitative disorder like Hb E variant & quantitative Hb disorder caused by genetic mutation of Beta chain. Objective: The aim of the study was to identify the beta gene mutation in Hb E/Beta thalassaemia. Method: A total of 32 diagnosed Hb E/Beta thalassaemia patients were included in this cross-sectional study from May 2019 to July 2020. Genetic analysis was done by sanger sequencing. Results: In this observational study, we found 13 different types of Beta gene mutations. Heterozygous for IVS 1-5(G>C) mutation was most frequent (53.1%). Conclusion: Genetic mutation is the confirmatory diagnosis for thalassaemia as well as one of the main factors for clinical expression. Mutation pattern also varies according to the geographical distribution. So, this study shows the frequently found mutation in Bangladesh and should carry out routinely to point out phenotypic expression.

scholarly journals Interaction of hemoglobin E and pyrimidine 5' nucleotidase deficiency

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2761-2767 ◽  
Author(s):  
DC Rees ◽  
J Duley ◽  
HA Simmonds ◽  
B Wonke ◽  
SL Thein ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Beta Thalassemia ◽  
Hemoglobin E ◽  
Oxidant Damage ◽  
Hb E ◽  
Hb Variant ◽  
Chain Synthesis ◽  
The Stability ◽  
Enzyme Deficient ◽  
Globin Chain Synthesis

A Bangladeshi family is described in which the genes for both hemoglobin E (Hb E) and pyrimidine 5′ nucleotidase deficiency are segregating. An individual homozygous for both these conditions has a severe hemolytic anemia, whereas family members who are homozygous for Hb E are asymptomatic and those homozygous for pyrimidine 5′ nucleotidase deficiency have the mild hemolytic anemia that is characteristic of this disorder. Globin-chain synthesis experiments have shown that the mechanism underlying the interaction between these two genotypes is a marked decrease in the stability of Hb E in pyrimidine 5′ nucleotidase-deficient red blood cells (RBCs). It has also been found that in the enzyme-deficient RBCs in which Hb E is highly unstable, free alpha-chains, though not beta E-chains, acoumulate on the membrane. In view of the increasing evidence that the hemolysis associated with pyrimidine 5′ nucleotidase deficiency results not only from an increase in the level of erythrocyte pyrimidines, but also from inhibition of the hexose monophosphate shunt activity in young erythrocytes, it is likely that the marked instability of Hb E in the enzyme-deficient cells results from oxidant damage acting on a mildly unstable Hb variant. These observations may have important implications for the better understanding of the pathophysiology of Hb E/beta-thalassemia, globally the commonest important form of thalassemia.

scholarly journals MOLECULAR ANALYSIS OF NON-TRANSFUSION DEPENDENT THALASSEMIA ASSOCIATED WITH HEMOGLOBIN E-β-THALASSEMIA DISEASE WITHOUT α--THALASSEMIA

2019 ◽  
Vol 11 (1) ◽  
pp. e2019038 ◽  
Author(s):  
Paramee Phanrahan ◽  
Supawadee Yamsri ◽  
Nattiya Teawtrakul ◽  
Goonnapa Fucharoen ◽  
Kanokwan Sanchaisuriya ◽  
...  
Keyword(s):  
Dna Analysis ◽  
Globin Gene ◽  
Phenotypic Expression ◽  
Nucleotide Polymorphisms ◽  
Thalassemia Patient ◽  
Hemoglobin E ◽  
Modifying Factors ◽  
Myb Gene ◽  
Hb E ◽  
Klf1 Gene

Background: The finding of many Thai Hb E-β0-thalassemia patients with non-transfusion dependent thalassemia (NTDT) phenotype without co-inheritance of α-thalassemia has prompted us to investigate the existence of other genetic modifying factors. Methods: Study was done on 146 adult Thai patients with NTDT Hb E-β0-thalassemia and a homozygous β-thalassemia patient without co-inheritance of α-thalassemia. Multiple single-nucleotide polymorphisms (SNPs) associated with γ-globin gene expression including the Gγ-XmnI of HBG2 gene, rs2297339, rs4895441, and rs9399137 of the HBS1L-MYB gene, rs4671393 in the BCL11A gene, and G176AfsX179, T334R, R238H and -154 (C-T) in the KLF1 gene were investigated using PCR-and related techniques. Results: Heterozygous and homozygous for Gg-XmnI of HBG2 gene were detected at 68.0% and 6.1%, respectively. Further DNA analysis identified the rs2297339 (C-T), rs4895441 (A-G), and rs9399137 (T-C) of HBS1L-MYB gene in 86.4%, 22.5% and 20.4%, respectively. The rs4671393 (G-A) of the BCL11A gene was found at 31.3%. For the KLF1 gene, the T334R and G176AfsX179 (+/-) were detected at 8.2% and 1.4%, respectively. Conclusion: It was found that these SNPs when analyzed in combination could explain the mild phenotypic expression of all cases. These results underline the importance of these informative SNPs on phenotypic expression of Hb E-β-thalassemia patients.

scholarly journals Hydroxyurea increases hemoglobin F levels and improves the effectiveness of erythropoiesis in beta-thalassemia/hemoglobin E disease

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 887-892 ◽  
Author(s):  
S Fucharoen ◽  
N Siritanaratkul ◽  
P Winichagoon ◽  
J Chowthaworn ◽  
W Siriboon ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Beta Thalassemia ◽  
Limited Information ◽  
Cell Disease ◽  
Hemoglobin F ◽  
Hemoglobin E ◽  
Globin Chains ◽  
Hb E ◽  
Alpha Globin

Hydroxyurea (HU) is one of several agents that have been shown to enhance hemoglobin (Hb) F levels in patients with sickle cell disease and may be useful as a therapy for beta-globinopathies. However, limited information exists on the effects of HU in patients with thalassemia. Accordingly, we examined the hematologic effects of orally administered HU in 13 patients with beta-thalassemia/Hb E, including four patients who had been splenectomized. These patients were treated with escalating doses (final range, 10 to 20 mg/kg/d) for 5 months and were observed in the outpatient hematology clinic every 2 to 4 weeks. Complete blood counts including reticulocyte counts, amounts of Hb E and Hb F, G gamma:A gamma and alpha:non-alpha globin biosynthetic ratios were evaluated before and during treatment. Almost all patients responded with an average increase of 33% in Hb F levels, from a mean (+/- SD) of 42% +/- 11% to 56% +/- 8% (P < .0001), and a reciprocal decline in the percentage of Hb E from 59% +/- 9% to 49% +/- 8% (P < .001). Reticulocytosis was decreased from a mean (+/- SD) of 18.0% +/- 15.6% to 11.7% +/- 9.1% (P < .05); there was also a slight (10%) but statistically significant increase in hemoglobin levels and an improved balance in alpha:non-alpha globin chains ratios. The side effects were minimal in most patients, although these patients tended to tolerate a lower dose of HU before significant myelosuppression than has been our previous experience in sickle cell disease. One splenectomized patient died of sepsis during the trial. We conclude that increased Hb F production in beta-thalassemia/Hb E patients, with an improvement in the alpha:non-alpha globin ratios and, probably, the effectiveness of erythropoiesis, can be achieved using HU. Longer trials of HU in this population, including at other doses and in combination with other agents, appear warranted.

scholarly journals TALASEMIA BETA HEMOGLOBIN E (Hemoglobin E Beta Thalassemia)

2018 ◽  
Vol 21 (3) ◽  
pp. 309
Author(s):  
Viviyanti Zainuddin ◽  
Agus Alim Abdullah ◽  
Mansyur Arif
Keyword(s):  
Laboratory Tests ◽  
Clinical Manifestations ◽  
Hypochromic Anemia ◽  
Peripheral Blood Smear ◽  
Beta Thalassemia ◽  
Hemoglobin Variant ◽  
Thalassemia Patient ◽  
Hemoglobin E ◽  
Polypeptide Chains ◽  
Additional Therapy

Thalassemia is a quantitative abnormality of the hemoglobin marked by inadequate hemoglobin synthesis due to the lack orabsence of synthesis of one or more globin polypeptide chains. Hemoglobin variant is a qualitative abnormality due to the presence ofthe abnormal amino acid sequence of one or more globin polypeptide chains. HbE β thalassemia is a disorder of hemoglobin that resultsfrom the fusion between the gene β-thalassemia allele from one parent with a gene HbE allele from another parent. In this case, HbEβ-Thalassemia patient was a 4.8 year girl diagnosed with hemoglobin E-beta thalassemia based on history and clinical manifestations;pale, the presence of splenomegaly and hepatomegaly. Laboratory tests were Hb: 7.7 g/dL, MCV: 52.9 fl, MCH: 17.7 pg, MCHC: 33.5g/dL and ferritin: 1012 ng/mL. Peripheral blood smear evaluation showed a microcytic hypochromic anemia with hemolytic signs andinfected features of leukocytes. Hb electrophoresis using HPLC showed a Hb F: 37.7% and HbA2 52.4%, indicating that HbA2 was falsehigh due to coeluating with HbE. The patient was treated by blood transfusion and received additional therapy such as folic acid, ironchelation and vitamin E.

Molecular Analysis of Alpha Hemoglobin Stabilizing Protein (AHSP) in Caucasian Patients with different Beta-Thalassemia Phenotypes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3770-3770 ◽  
Author(s):  
M. Domenica Cappellini ◽  
Chiara Refaldi ◽  
Daniela Bignamini ◽  
Laura Zanaboni ◽  
Gemino Fiorelli
Keyword(s):  
High Performance ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Clinical Severity ◽  
Beta Thalassemia ◽  
Red Cell ◽  
Globin Genes ◽  
Nucleotide Polymorphisms ◽  
Thai Population ◽  
Globin Chains

Abstract Beta-thalassemia is a inherited hemoglobin disorder characterized by absent or reduced synthesis of the b globin chains. The pathophysiology and the severity of b-thalassemias reflect the degree of globin chain imbalance and the excess of free a globin chains that precipitate and cause oxidative damage in red cell precursors inducing their premature destruction in the bone marrow (ineffective erythropoiesis). Although the phenotype of b thalassemias can be modified by inherited factors such as different number of a globin genes or increased fetal hemoglobin production, other mechanisms appear to be involved. Recently, a protein, named alpha hemoglobin stabilizing protein (AHSP), that acts as a molecular chaperone specifically for free a globin chains, preventing their precipitation in red cell precursors, has been identified. To establish whether AHSP might have a role in modifying the clinical outcome of b thalassemias, we have analyzed the AHSP gene in 70 Caucasian b thalassaemic subjects: 26 patients with b°/b° genotype (Thalassaemia Major),24 patients with Thalassemia Intermedia (b°/b+ or b+/b+) and 20 patients with a Thalassaemia Intermedia phenotype but with only one mutation in the b globin gene, a normal a globin genotype and no other causes of anemia. In all the subjects, we have performed Denaturing High-Performance Liquid Chromatography (DHPLC) of the three exons and the direct genomic sequencing of coding and noncoding regions (~ 1.5 kb) of AHSP gene. No mutations able to modify the structure or function of AHSP have been found, however we identified eight single nucleotide polymorphisms (SNPs) spanned along the whole gene that segregate in four different aplotypes. To evaluate a possible relationship between a particular aplotype and b thalassemia severity, the allele frequency of each single aplotype in the tree groups has been established and compared to that of 33 Caucasian normal controls: no statistically significant association has been proved. Even though the loss of AHSP aggravates the b thalassaemia phenotype in mice, in Thalassemic Caucasian population the AHSP apparently doesn’t make changes in the clinical severity of b thalassemia confirming the results recently found in Thai population.

Study of distribution of ABO blood groups in ß-thalassemia patients

2017 ◽  
Vol 5 (8) ◽  
pp. 3479 ◽  
Author(s):  
Pranoti A. Sinha ◽  
Sachin H. Mulkutkar ◽  
J. B. Bhavani
Keyword(s):  
Blood Group ◽  
Late Onset ◽  
Blood Groups ◽  
Beta Thalassemia ◽  
Abo Blood Groups ◽  
Thalassemia Patient ◽  
Cross Sectional ◽  
Globin Chains ◽  
Institutional Ethics ◽  
History Of

Background: ß-thalassemia is an inherited hematological disorder caused by reduced or absent synthesis of ß globin chains of the hemoglobin which causes hemolysis and impair erythropoiesis. Affected children thus require regular lifelong blood transfusions. Blood group is one of the important and comparatively known parameter today which exhibits a strong correlation with some common diseases like cardiovascular diseases, gastric cancer, HIV infection etc. Aim of this study hence was to study relation between ABO blood groups and ß-thalassemia and to study complications in each blood groups to make it easy to predict the type of population which is more prone or resistant to ß-thalassemia for understanding the regional demand of rare blood groups and to tide over the demands.Methods: This was a cross sectional, single centric, open labeled, observational study in which 100 patients of ß-thalassemia were screened for their ABO blood groups after permission from institutional ethics committee and informed consent from the patient.Results: Most common blood group in ß-thalassemia patient is O +ve. Post-disease complication is commonly seen with B +ve. Early onset of beta-thalassemia is seen in A +ve and B +ve. Late onset is seen with O +ve. Severity more with B –ve while O +ve shows disease in less severe form.Conclusions: On analysis, it was found that the most common blood group getting affected by the disease ß-thalassemia is O +ve with the same people having higher chances of family history of the same disease. Within the family members who have the positive history of the disease, most common was O +ve blood group again.

scholarly journals Clinical Profile of Thalassemia Syndrome in Children of Northern Bangladesh

2019 ◽  
Vol 31 (2) ◽  
pp. 6-11
Author(s):  
Md Rustam Ali ◽  
Md Iqbal Bari ◽  
Md Sanaul Haque Mia ◽  
Md Khalilur Rahman ◽  
Md Farid Hossain ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Standard Procedure ◽  
Iron Chelation ◽  
Hemoglobin Concentration ◽  
Folic Acid Supplementation ◽  
Beta Thalassemia ◽  
Low Grade ◽  
Thalassemia Patient ◽  
Racial Background ◽  
Hb E

Background: Thalassemia is a common hematological disorder in our country having wide spectrum of clinical presentation. The frequency and severity of the several types of thalassemia depend on the racial background of the population. Hb-E Beta thalassemia is prevalent in our country. Objective: To see the clinical features of different types of Thalassemia in northern area of Bangladesh. Methods: Hundred cases were selected from Thalassemia patient admitted in department of pediatrics, on May 2012 to October 2012. A prescribed questionnaire was used to record the information. The methods were explained to the patients and consent was taken. Necessary physical examination was performed and investigations were done. The data was analyzed by standard procedure. Results: Out of hundred (100) cases, most (61%) were Hb-E beta Thalassemia, less common (1%) was Hb-E disease, and 1 % case was Hb-E trait. Majority (64%) manifested clinically under one year of age. 54% were male and 46% were female. The major presenting symptom was progressive pallor in 70% cases. Others presenting complaints were low grade fever (40%). Hemoglobin concentration at the time of diagnosis was below 5 gm/dl in 53.33% patients. In hemoglobin electrophoresis it was Hb-E ranged from 54.64 ± 13.02%, Hb-F 34.84±13.73%, Hb-A 23.32± 18.15% and Hb-A2 3.5± 70%. Radiological findings revealed gross bony changes occur in long standing cases. Enlarged cardiac shadow was found in those cases having severe anemia with heart failure. Conclusion: In countries with a high incidence of thalassemia, it is vitally important to offer prospective genetic counseling and to warn carriers about the risks of intramarriage. Nutritional and folic acid supplementation with regular blood transfusion along with iron chelation therapy is essential to improve the prognosis. TAJ 2018; 31(2): 6-11

Hypercoagulable state as demonstrated by thromboelastometry in hemoglobin E/beta-thalassemia patients: Association with clinical severity and splenectomy status

2016 ◽  
Vol 140 ◽  
pp. 125-131 ◽  
Author(s):  
Rungrote Natesirinilkul ◽  
Pimlak Charoenkwan ◽  
Weerasak Nawarawong ◽  
Settapong Boonsri ◽  
Pakinee Tantivate ◽  
...  
Keyword(s):  
Clinical Severity ◽  
Hypercoagulable State ◽  
Beta Thalassemia ◽  
Hemoglobin E

scholarly journals High Performance Liquid Chromatography (HPLC) Screening among Filipinos with Suspected Thalassemia

2020 ◽  
Vol 54 (4) ◽  
Author(s):  
Terence Diane F. Fabella ◽  
Catherine Lynn T. Silao ◽  
Maria Liza T. Naranjo ◽  
Carmencita D. Padilla ◽  
Ernesto DJ Yuson
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Ethylenediaminetetraacetic Acid ◽  
Clinical Manifestations ◽  
The Philippines ◽  
Beta Thalassemia ◽  
Mean Corpuscular Hemoglobin ◽  
Blood Samples ◽  
Hb E

Introduction. Thalassemias and hemoglobinopathies are autosomal-recessive red blood cell disorders affectinghemoglobin (Hb) quantity and/or quality. Clinical manifestations vary from clinically asymptomatic to transfusion dependent individuals. These disorders are global in scope and is prevalent in Southeast Asia hence screening in the Philippines is very crucial for its prevention and control.Objective. Our retrospective study aimed to determine the frequency of thalassemias and hemoglobinopathies in patients referred to the Molecular Genetics Unit, Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila for High Performance Liquid Chromatography (HPLC) screening.Methods. Blood samples from patients (n=622) sent by hematologists from different parts of the country from October 2008 to February 2015 were analyzed. Extracted whole blood samples from the subjects were anticoagulated with ethylenediaminetetraacetic acid (EDTA) and were analyzed using BIORAD VARIANT™ HPLC Testing System and VARIANT™ Beta Thalassemia Short (BTS) Program kit for the detection of abnormalities in hemoglobin. Interpretation of results were based on the submitted mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) values, and Hb typing via HPLC of the patients.Results. Approximately twenty-nine percent (29.10%, n=181) of subjects were presumptively identified with thalassemias and hemoglobinopathies by HPLC. Beta-thalassemia trait, Hb E trait, and beta-thalassemia/Hb E disease were detected in 65 (10.45 %), 14 (2.25 %), and 3 (0.48 %) subjects, respectively. While suspected alpha-thalassemia, presumably Hb H disease, was found in 99 (15.92 %) patients. Interestingly, seventy-two percent (72.11%, n=318) of the patients with normal Hb typing via HPLC have low MCV and MCH values.Conclusion. Results of this study provide the spectrum and frequency of thalassemias and hemoglobinopathies in patients referred to our laboratory for HPLC analysis.

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