Year : 2009 | Volume
: 52 | Issue : 1 | Page : 110--112
Hemoglobin E disorders in Eastern Uttar Pradesh
Shashikant C.U Patne, Jyoti Shukla
Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221005, Uttar Pradesh, India
Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, Uttar Pradesh
The distribution of hemoglobin E (α2β2 26Glu«Lys ) is mostly restricted to Northeastern India. While evaluating the patients of jaundice, we came across two cases of hemoglobin E (Hb E) disorders. The first case is in a 22-year-old Bengali male and the second case of Hb E/β thalassemia in a 5-year-old Hindu boy. The family study revealed Hb E trait in both the parents of Case 1, whereas in Case 2, the father was found to have Hb E trait and the mother had β -thalassemia minor, thus confirming the diagnosis. Herein, we present the laboratory diagnosis and comparative data of the spectrum of Hb E disorders (i.e., heterozygous Hb E trait, homozygous Hb E disease and compound heterozygous Hb E/β -thalassemia) that was found in our index cases and their parents.
|How to cite this article:|
Patne SC, Shukla J. Hemoglobin E disorders in Eastern Uttar Pradesh.Indian J Pathol Microbiol 2009;52:110-112
|How to cite this URL:|
Patne SC, Shukla J. Hemoglobin E disorders in Eastern Uttar Pradesh. Indian J Pathol Microbiol [serial online] 2009 [cited 2022 Jun 29 ];52:110-112
Available from: https://www.ijpmonline.org/text.asp?2009/52/1/110/44991
Hemoglobinopathies are genetically important hematological disorders affecting millions of people worldwide. The cumulative gene frequency of hemoglobinopathies in India is 4.2%.  The prevalence of hemoglobinopathies varies with the geographic locations and ethnic groups. Among the clinically important hemoglobinopathies (Hb S, Hb D, Hb E and thalassemias), hemoglobin E (Hb E) is mostly restricted to the Northeastern states of India i.e., West Bengal, Assam Andhra Pradesh, Nagaland, Manipur, Tripura and Meghalaya with an average allele frequency of 10.9%.  Hb E disorders may be found in heterozygous (AE), homozygous (EE) and compound heterozygous states (e.g., Hb E with other abnormal hemoglobins or thalassemias) with widely variable clinical phenotypes.
While evaluating the patients of jaundice, we came across two cases of Hb E disorders from two unrelated families-a 22-year-old Bengali male with homozygous Hb E disease and a 5-year-old Hindu boy with Hb E/β-thalassemia. The family study revealed Hb E trait in both the parents of Case 1 and the Hb E trait in the father and β-thalassemia minor in the mother of Case 2. As a wide spectrum of clinical phenotypes have been observed in various forms of Hb E disorders  , this prompted us to present the clinico-hematological findings of our patients and their parents for comparative evaluation.
A 22-year-old Bengali Hindu male, a migrant from West Bengal and the only child of his parents, presented with abdominal pain on the left side, diarrhea and recurrent attacks of fever and jaundice. On examination, he had mild hepatosplenomegaly. Investigations revealed a serum bilirubin level of 2.7 mg/dL (indirect 1.8 mg/dL;direct 0.9 mg/dL), a hemoglobin level of 12 g/dL, a total leucocyte count (TLC) of 10.6X10 3 /ÁL, a differential leucocyte count (DLC) - N 72 L 25 E 2 M 1 , platelet count of 220X10 3 /ÁL and a reticulocyte count of 3.5%. The general blood picture showed mild anisopoikilocytosis of red blood cells (RBCs) with the presence of microcytes, target cells and hypochromia. Tests for G6PD, sickling, Coomb's and osmotic fragility were normal. Fetal hemoglobin done by alkali denaturation method was less than 1%. Hemoglobin electrophoresis on 1% agarose gel at alkaline pH (8.6) showed a thick single band at Hb A 2 /E region, with the absent Hb A band, suggesting a diagnosis of homozygous Hb E disease (EE). The parents, although completely asympotomatic, were investigated similarly. Both of them showed two bands on the hemoglobin electrophoresis corresponding at the Hb A and Hb A 2 /E regions suggesting the Hb E trait. The findings were also confirmed by a high performance liquid chromatography (HPLC) analysis.
A 5-year-old Hindu boy, a resident of Uttar Pradesh, presented with severe anemia, jaundice, growth retardation and typical hemolytic facies. He was given two units of whole blood transfusion 1 month earlier. The examination of the patient revealed marked splenomegaly (11 cm) and mild hepatomegaly (3 cm). Investigations revealed a serum bilirubin level of 5.8 mg/dL (indirect 4.2 mg/dL;direct 1.6 mg/dL), a hemoglobin level of 5.5 g/dL, a TLC of 8.5x10 3 /ÁL, DLC-N 40 L 50 E 5 M 4 B 1 , platelet count of 260x10 3 /ÁL and a reticulocyte count of 30%. The general blood picture showed severe anisopoikilocytosis of the RBCs with the presence of a fair number of microcytes, target cells, tear drop cells, schistocytes and marked hypochromia. Nucleated RBCs were 20/100 white blood cells (WBCs). Tests for G6PD, Coomb's and sickling were negative. Osmotic fragility was decreased (lysis started at 0.40 g% sodium chloride solution as opposed to control, where it started at 0.50 g%). Hemoglobin electrophoresis on 1% agarose gel at alkaline pH (8.6) revealed two bands corresponding at the position of Hb A2 /E and the other at Hb F. Fetal hemoglobin by alkali denaturation method was 24.6%. Thus, a diagnosis of Hb E/b-thalassemia was made. The patient's family history revealed that his elder brother died at the age of 10 years. He had similar problems as that of the index case and was dependent on blood transfusions. Details of his investigations were not available. His parents were studied for their hematological indices and hemoglobin electrophoresis was performed in the similar way at our laboratory. An electrophoretogram of the father revealed an AE pattern (Hb E trait), whereas electro phoretogram of the mother came as normal (AA pattern). Because our previous experience of diagnosing the β-thalassemia trait on agarose gel was not good, we insisted that the parents go elsewhere for a HPLC analysis. The HPLC analysis confirmed β-thalassemia minor (β-thalassemia trait) in the mother.
All the hematological indices, electrophoretic findings and HPLC values of our patients (Case 1 and Case 2) and their parents are presented in [Table 1]. [Figure 1A] and [Figure 1B] show the electrophoretograms of the patients and [Figure 2] shows the family tree of Case 2.
Thalassemias and hemoglobinopathies are autosomal recessive inherited disorders, primarily affecting the globin moiety of the hemoglobin molecule. These disorders, which were mainly confined to certain areas, religions, castes and tribes particularly with endogamous norms of marriages, are now widely prevalent all over the world. This is because of the ever increasing migration of people from one place to another and the mixing of different communities through marriages. The presence of Hb E was mainly restricted to the Northeastern states of India with only occasional case reports from other parts of the country including Uttar Pradesh.  However, recent studies show an increasing frequency of Hb E and thalassemias in Eastern Uttar Pradesh and the adjoining areas. , Among 120 cases of thalassemias and abnormal hemoglobins, Sinha, et al  reported 66.9% and 15.9% cases of thalassemias and Hb E disorders, respectively. As part of the antenatal screening program for thalassemias and hemoglobinopathies, we found 5.8% of pregnant women with the β-thalassemia trait and 0.8% with the Hb E trait.  Clinical phenotypes of Hb E disorders particularly Hb E /β-thalassemia is quite variable.  Individuals with the Hb E Trait are usually not anemic and have no symptoms. Hematological investigations of these individuals reveal mild microcytosis, hypochromia and erythrocytosis as seen with the β-thalassemia trait. However, identification of these individuals is of crucial importance as they may be transmitters of the abnormal gene, giving rise to various combinations of hemoglobinopathies and thalassemias in their progeny. The presentation of Hb E disease is mild to moderate. Most patients show clinical symptoms by the age of 10 years. The most common presentation of Hb E disease is no or mild anemia, jaundice, fever, abdominal pain and gastrointestinal disturbances with or without splenomegaly. The blood picture shows microcytic hypochromic red cells with or without any evidence of hemolysis. In a study from CMC Vellore,  it was observed that most of the patients with Hb E disease present themselves for recurrent episodes of jaundice. This also occurred in our cases. This finding of unconjugated hyperbilirubinaemia was attributed to the variant TA7 in the promoter region of the UGT1A1 gene. The clinical picture of Hb E/β-thalassemia is variable, ranging from β-thalassemia minor through β-thalassemia intermedia to β-thalassemia major, but most of the patients have moderately severe disease.  Nadkarni, et al  in their study observed that the co-inheritence of deletional α-thalassemia and the presence of -158 G gamma (C->T) substitution decreases the severity of the disease more than the nature of β-thalassemia mutation. These new insights into the knowledge of these diseases are important because they are gradually becoming global health problems and impart diagnostic challenges to all the experts involved in the treatment of patients with thalassemia.
|1||Sarnaik SA. Thalassemia and related hemoglobinopathies. Indian J Pediatr 2005;72:319-24.|
|2||Balgir RS. Genetic epidemiology of the three predominant abnormal hemoglobins in India. J Assoc Physicians India 1996;44:25-8.|
|3||Fucharoen S, Ketvichit P, Pootrakul P, Siritanaratkul N, Piankijagum A, Wasi P. Clinical manifestation of beta-thalassemia/hemoglobin E disease. J Pediatr Hematol Oncol 2000;22:552-7.|
|4||Gupta SC, Mehrotra TN, Mehrotra VG. Haemoglobin-E-thalassemia in Uttar Pradesh. Indian J Med Res 1970;58:857-62.|
|5||Sinha S, Kumar A, Gupta V, Kumar S, Singh VP, Raman R. Haemoglobinopathies-thalassemias and abnormal haemoglobins in eastern Uttar Pradesh and adjoining districts of neighbouring states. Curr Sci 2004;87:775-80.|
|6||Sinha M, Panigrahi I, Shukla J, Khanna A, Saxena R. Spectrum of anemia in pregnant Indian women and importance of antenatal screening. Indian J Pathol Microbiol 2006;49:373-5.|
|7||Fairbanks VF, Gilchrist GS, Brimhall B, Jereb JA, Goldston EC. Hemoglobin E trait reexamined: A cause of microcytosis and erythrocytosis. Blood 1979;53:109-15.|
|8||Edison ES, Shaji RV, Srivastava A, Chandy M. Hyperbilirubinemia in homozygous Hb E disease is associated with the UGT1A1 gene polymorphism. Hemoglobin 2005;29:189-95. |
|9||Bachir D, Galacteros F. Hemoglobin E disease. Orphanet encyclopedia. Available from: http://www.orpha.net/data/patho/GB/uk-HbE.pdf. [cited on 2004 Nov].|
|10||Nadkarni A, Ghosh K, Gorakshakar A, Colah R, Mohanty D. Variable clinical severity of Hb E beta-thalassemia among Indians. J Assoc Physicians India 1999;47:966-8.|