Molecular analysis of the beta-thalassemia phenotype associated with inheritance of hemoglobin E (alpha 2 beta2(26)Glu leads to Lys).

Beta thalassemia (β-thal) is one of the most common worldwide inherited hemoglobinopathies. Proper identification and diagnosis of hemoglobin (Hb) variants provide a major challenge. In this report, we describe a 1-year-old boy, presented with the diagnosis of β-TM (beta thalassemia major), has received regular blood transfusions. The molecular analysis revealed the presence of rare Hb Castilla [Beta 32(B14) Leu>Arg; HBB: c.98T>G] variant associated with β0 [IVS-I-1 (G>A); AG^GTTGGT- >AGATTGGT beta0] (HBB:c.92+1G>A) Mutation in beta-globin (β-globin) gene. To our knowledge, this is the first report of Hb Castilla [Beta 32(B14) Leu>Arg] in ExonII of β-globin gene which were found in Syrian male proband. However, we should investigate abnormal hemoglobins in patients with beta thalassemia to determine whether they have involvement with β-thalassemia mutations in the clinical case of the patients or not.

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Interaction of hemoglobin E and pyrimidine 5' nucleotidase deficiency

Blood ◽

10.1182/blood.v88.7.2761.bloodjournal8872761 ◽

1996 ◽

Vol 88 (7) ◽

pp. 2761-2767 ◽

Cited By ~ 26

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.

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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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