Correlation of BACH1 and Hemoglobin E/Beta-Thalassemia Globin Expression

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.

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

Blood ◽

10.1182/blood.v87.3.887.bloodjournal873887 ◽

1996 ◽

Vol 87 (3) ◽

pp. 887-892 ◽

Cited By ~ 88

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.

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Treatment strategies for hemoglobin E beta-thalassemia

Blood Reviews ◽

10.1016/s0268-960x(12)70009-7 ◽

2012 ◽

Vol 26 ◽

pp. S28-S30 ◽

Cited By ~ 9

Author(s):

Nancy F. Olivieri

Keyword(s):

Treatment Strategies ◽

Beta Thalassemia ◽

Hemoglobin E

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DISCREPANCY BETWEEN HAEMOGLOBIN, RDW, AND MEAN CORPUSCULAR VALUES IN PATIENTS WITH BETA THALASSEMIA / HEMOGLOBIN E DISEASE AND BETA THALASSEMIA TRAIT

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v25i3.1459 ◽

2019 ◽

Vol 25 (3) ◽

pp. 343

Author(s):

Vinisia Setiadji ◽

Bidasari Lubis ◽

Adi Koesoema Aman ◽

Herman Hariman

Keyword(s):

Beta Thalassemia ◽

Hemoglobin E ◽

Thalassemia Trait ◽

Hemoglobin E Disease

Thalassemia beta / hemoglobin E adalah suatu kondisi dengan heterozigot ganda gen pembawa thalassemia beta dan hemoglobin E. Hal ini menyebabkan kondisi dengan gambaran fenotip yang berat dibandingkan trait thalassemia beta dan trait hemoglobin E. Secara logika, nilai mean corpuscular dari thalassemia beta / hemoglobin E seharusnya memburuk. Pada penelitian ini, kami meneliti sebelas kasus dari dua keluarga dengan anggota menderita thalassemia beta / hemoglobin E.Pada keluarga-1 dua anggota dengan trait thalassemia beta memiliki nilai MCV 68 fL dan 65 fL, dan nilai MCH 21 pg dan 20 pg. Pada keluarga-2 anggota dengan trait thalassemia beta memiliki nilai MCV 60,2 fL dan MCH 18,8 pg. Anak perempuan dari kedua keluarga dengan thalassemia beta / hemoglobin E memiliki nilai mean ± SD MCV 70,8 ± 4,9 fL dan MCH 22.8 ± 2.3 pg, nilai ini signifikan lebih tinggi daripada trait thalassemia beta (p<0.05). Terdapat perbedaan yang signifikan antara nilai hemoglobin dan RDW antara thalassemia beta / hemoglobin E (p=0.001).Kami juga menemukan bahwa nilai MC dari keadaan post-transfusi signifikan lebih tinggi daripada pre-transfusi (p<0.001)Kami menyimpulkan bahwa nilai MC dari thalassemia beta / hemoglobin E secara persisten lebih tinggi daripada trait thalassemia beta. Peran transfusi darah pada pasien dengan thalassemia beta / hemoglobin E tampak memainkan peran dalam diskrepansi pada kasus ini.

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TALASEMIA BETA HEMOGLOBIN E (Hemoglobin E Beta Thalassemia)

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v21i3.1286 ◽

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.

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A Rare Case of Hemoglobin E/Beta-Thalassemia and Systemic Lupus Erythematosus

Cureus ◽

10.7759/cureus.10332 ◽

2020 ◽

Author(s):

Ibrahim Khamees ◽

Ibrahim Mohammad Obeidat ◽

Waail Rozi ◽

Mohamed A Yassin

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Rare Case ◽

Beta Thalassemia ◽

Systemic Lupus ◽

Hemoglobin E

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Double heterozygous for hemoglobin E and Beta thalassemia: A case study

International Journal of Clinical and Diagnostic Pathology ◽

10.33545/pathol.2020.v3.i1e.187 ◽

2020 ◽

Vol 3 (1) ◽

pp. 296-298

Author(s):

FJ Goswami1 ◽

RK Gidwani ◽

NV Shah ◽

MM Shah ◽

SA Prajapati

Keyword(s):

Beta Thalassemia ◽

Hemoglobin E

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

10.21203/rs.3.rs-927268/v1 ◽

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.

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