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 Table of Contents  
Year : 2022  |  Volume : 13  |  Issue : 1  |  Page : 1-4

Delta beta thalassemia, a rare hemoglobin variant: An experience from nodal centre in North Indian state

Department of Pathology, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana, India

Date of Submission10-Oct-2020
Date of Decision16-Jan-2021
Date of Acceptance06-Mar-2021
Date of Web Publication28-Apr-2022

Correspondence Address:
Dr. Niti Dalal
Department of Pathology, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joah.joah_198_20

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CONTEXT: Fetal hemoglobin (HbF) reduces to <1% few months after birth. However, it can persist beyond infancy into adult life in rare conditions such as delta-beta (δβ) thalassemia and hereditary persistence of HbF. δβ thalassemia is a relatively rare type of thalassemia due to decrease in both beta and delta globin chain production.
AIMS: This study aims to assess the hematological and high-performance liquid chromatography (HPLC) findings in δβ thalassemia.
SETTINGS AND DESIGN: Cross-sectional observational study.
SUBJECTS AND METHODS: The study was conducted in department of Clinical Pathology, PGIMS, Rohtak. On screening of 1197 patients over a period of around 1 year, a total of 13 cases of δβ thalassemia were detected by HPLC.
RESULTS: The age of presentation ranged from 1 to 42 years with a mean age of 22.8 years. Eleven cases were diagnosed as heterozygous δβ thalassemia and two as homozygous δβ thalassemia.
CONCLUSIONS: δβ thalassemia is an uncommon cause of elevated HbF. Clinical and hematological parameters should be carefully analyzed for accurate diagnosis.

Keywords: Delta-beta thalassemia, fetal hemoglobin, heterozygous, high-performance liquid chromatography, homozygous

How to cite this article:
Jain P, Marwah N, Dalal N, Pawar R, Gill M, Kumar S. Delta beta thalassemia, a rare hemoglobin variant: An experience from nodal centre in North Indian state. J Appl Hematol 2022;13:1-4

How to cite this URL:
Jain P, Marwah N, Dalal N, Pawar R, Gill M, Kumar S. Delta beta thalassemia, a rare hemoglobin variant: An experience from nodal centre in North Indian state. J Appl Hematol [serial online] 2022 [cited 2023 Jun 4];13:1-4. Available from: https://www.jahjournal.org/text.asp?2022/13/1/1/344260

  Introduction Top

Delta-beta (δβ) thalassemia is rare autosomal recessive condition with reduced δ, β-globin genes, compensatory increased γ-globin chains leading to raised Fetal hemoglobin (HbF) levels even beyond infancy.[1],[2] Genetically, it could either be δβ thalassemia heterozygous or homozygous.[2] Clinically, homozygotes are similar to β-thalassemia intermedia with mild anemia and 100% HbF, while heterozygotes show features of β-thalassemia trait, and normal HbA2 and consistently elevated levels of HbF (5%–20%). Differential diagnosis includes hereditary persistence of HbF where patients are asymptomatic with nearly 100% HbF in homozygous and 17%–30% in heterozygous hereditary persistence of fetal hemoglobin (HPFH).[3],[4],[5],[6] The aim of study is to assess hematological profile and high-performance liquid chromatography (HPLC) findings in δβ thalassemia.

  Subjects and Methods Top

The study was conducted in the Department of Clinical Pathology, PGIMS, Rohtak over a time period of 1 year, i.e., from March 2019 to March 2020 on 1197 anemic patients. Complete blood count was done on all samples on Mindray automated 6 part cell counter. Hemoglobin, red blood cell (RBC) indices, RBC count, Red cell distribution width (RDW) and reticulocyte count were studied. These samples were further evaluated for presence of any hemoglobinopathy on HPLC (Biorad variant II short program). Percentage of HbA, HbA2, HbF or any other abnormal hemoglobin was noted in each case as per retention time on chromatogram. Patients with HbA2 levels between 4% and 9% were labeled as beta thalassemia trait. Anemic patients more than 1 year of age with persistently high HbF and normal HbA2 were diagnosed as δβ thalassemia [Table 1]. Then, depending on the level of HbF, these patients were further categorized as heterozygous (HbF 5%–20%) or homozygous δβ thalassemia (HbF levels >90%) [Figure 1] and [Figure 2].
Table 1: Complete blood count and high-performance liquid chromatography findings

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Figure 1: High-performance liquid chromatography of delta-beta thalassemia homozygous

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Figure 2: High-performance liquid chromatography of delta-beta thalassemia heterozygous

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  Results Top

A total of 1197 samples from patients with low hemoglobin were screened from March 2019 to March 2020 by high HPLC method for the presence of any hemoglobinopathy. Thirteen cases of δβ thalassemia were detected in the study besides detecting other hemoglobinopathies, out of which 6 were male and 7 were female. Mean age of these patients was 22.8 years including 9 adults and 4 children, out of which 3 children were <5 years and one was 11 years old. Six patients each had mild (Hb >10 gm%) and moderate (Hb >6 gm%) anemia and one patient had severe anemia (Hb <6 gm%) [Table 1]. All the 13 patients had microcytic picture (mean corpuscular volume [MCV] <80fl). Twelve out of these 13 patients had raised RDW-coefficient of variation (RDW-CV) ranging from 17.4% to 30.3%. HbF in all these 13 patients on HPLC ranged between 6.3% and 99%. Eleven out of 13 cases were diagnosed as heterozygous δβ thalassemia and two cases were homozygous δβ thalassemia. Cases of homozygous state presented with moderate degree of anemia. On HPLC, HbA levels ranged between 70% and 86% in all 11 cases of heterozygous state and <4% in two homozygous cases. HbF ranged between 6.3% and 18.5% in heterozygous cases and was 94.6% and 99% in homozygous cases [Table 1] and [Figure 1], [Figure 2]. Confirmation by molecular tests could not be done due to nonavailability of these tests in our institution and financial constraints of study population.

  Discussion Top

Thalassemia is a group of monogenic diseases found commonly in Africa, Middle East, India, South East Asia, Southern China, and Mediterranean region. These include α, β, δβ thalassemia as determined by type of globin chain that is involved.[7] β-thalassemia is the most common type of thalassemias especially β-thalassemia trait, in which HbA2 levels are raised (4.0%–9.0%), while δβ thalassemia is a rare entity. Characteristic finding of δβ-thalassemia is persistently high fetal hemoglobin and normal HbA2 levels in adults. HbF is a globular protein which contains two alpha and two gamma globin chains (α2 β2). Normally HbF levels decline to <1% 1 year after birth. However, the persistence of high levels of HbF in adults is seen in conditions such as δβ thalassemia and hereditary persistence of HbF.[8],[9] δβ thalassemia is characterized by decrease in both beta and delta globin chain production due to the deletion of δ and β globin genes on chromosome 11, with compensatory increase in production and expression of gamma genes on both the affected chromosomes of gamma globin, hence persistently increased HbF even post infancy.[5],[6] Nondeletional type of δβ thalassemia has also been described. This results from the presence of two different nucleotide substitutions in promoter region of Aγ and β-globin gene.[10] On the basis of globin chain synthesis, it was analyzed that α/non-α chain imbalance in δβ-thalassemia is less noticeable than in β-thalassemia. Mutations responsible for δβ-thalassemia have been observed in different ethnic groups such as Turkish, German, Japanese, Black, Sicilian, and Spanish.[11],[12] Unlike classical β-thalassemia, clinical presentation of δβ thalassemia is mild in both heterozygous and homozygous state. However, thalassemic red cell indices along with hemoglobin analysis by electrophoresis or HPLC showing elevated HbF with normal HbA2 in heterozygote and absence of HbA and HbA2 and nearly 100% HbF in homozygote patients help in reaching the diagnosis. Mutational analysis is confirmatory for the diagnosis. Clinical and hematological parameters of heterozygous δβ-thalassemia are similar to that of thalassemia minor (low MCV and mean corpuscular hemoglobin, consistently elevated HbF and normal or reduced HbA2 levels as against raised RBC count and HbA2 levels between 4% and 9% in β-thalassemia trait), whereas, patients with homozygous δβ-thalassemia present with thalassemia intermedia such as clinical picture and characteristic red cell morphology (high RBC and reticulocyte count with microcytic hypochromic picture with persistently nearly 100% HbF) and sometimes deranged liver function test showing increased indirect bilirubin and reduced serum haptoglobin. Homozygous δβ-thalassemia is also known as F-thalassemia, normal A2 β-thalassemia and β-thalassemia type 2.[4],[13] Complete absence of HbA with presence of HbF as the single or main hemoglobin component beyond fetal period also occurs in genetic disorders such as some variants of homozygous β-thalassemia, cases of double heterozygosity for δβ-thalassemia and classical β-thalassemia, patients with HPFH and homozygous δβ-thalassemia.[12] Homozygous δβ-thalassemia should be differentiated from homozygous HPFH, as both these disorders show more than 90% HbF and are non-transfusion dependent. Findings of mild anemia with hemolytic features like thalassemia intermedia favor the diagnosis of homozygous δβ-thalassemia whereas patients of homozygous HPFH are asymptomatic with normal hematology profile.[2],[3]

Moreover, in our study, we found that 12 out of 13 patients of δβ-thalassemia had raised RDW-CV. Our findings are consistent with the findings of Diego VR et al. who emphasized that RDW-CV is the best parameter to discriminate δβ-thalassemia from β-thalassemia trait as RDW-CV is normal in the later.[14]

Even on extensive PubMed search, the incidence and prevalence of δβ-thalassemia is limited to only a few isolated cases of δβ-thalassemia in literature. With improved technology and increased use of HPLC technique in many institutes in India, we can diagnose case of δβ-thalassemia better which is still considered a rare entity in our region, so a larger study, more awareness and clinical suspicion with long-term studies are required to know the exact prevalence in our country.

To the best of our knowledge, this is one very few studies reported so far in which so many cases of δβ-thalassemia are being bring forth.

  Conclusions Top

Since hemoglobin HPLC is becoming increasingly available at many institutions in India, this rare disorder with consistently raised HbF should be kept in mind while reporting, so that proper diagnosis, timely genetic counseling and treatment could be done for the better patient care.


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Conflicts of interest

There are no conflicts of interest.

  References Top

Wahed A, Quesada A, Dasgupta A. Hemoglobinopathies and thalassemias: Hematology and Coagulation. 2nd edition. Cambridge: Elsevier; 2020. 55-80. Available from: https://www.sciencedirect.com/science/ article/pii/B9780128149645000048.  Back to cited text no. 1
Sharma S, Sehgal S, Das R, Gulati S. Phenotypic heterogeneity of delta-beta thalassemia. Indian J Pathol Microbiol 2019;62:185-6.  Back to cited text no. 2
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Bollekens JA, Forget BG. Delta beta thalassemia and hereditary persistence of fetal hemoglobin. Hematol Oncol Clin North Am 1991;5:399-422.  Back to cited text no. 3
Kumar BV, Choccalingam C, Samuel P. Incidental identification of possible delta-beta thalassemia trait in a family: A rare cause of elevated hb f. J Clin Diagn Res 2016;10:BD01-2.  Back to cited text no. 4
Mansoori H, Asad S, Rashid A, Karim F. Delta beta thalassemia: A rare hemoglobin variant. Blood Res 2016;51:213-4.  Back to cited text no. 5
Bain BJ. Hemoglobinopathy Diagnosis. 2nd ed. Oxford, UK: Blackwell Publishing Ltd.; 2006. p. 116-24.  Back to cited text no. 6
Cao A, Kan YW. The prevention of thalassemia. Cold Spring Harb Perspect Med 2013;3:a011775.  Back to cited text no. 7
Stamatoyannopoulos G, Nienhuis AW. Hemoglobin switching. In: The Molecular Basis of Blood Diseases. 2nd ed. Philadelphia: WB Saunders Company Press; 1994. p. 107-55.  Back to cited text no. 8
Weatherall DJ, Clegg JB. The Thalassemia Syndromes. 4th ed. England: Oxford Blackwell Science; 2001.  Back to cited text no. 9
Ottolenghi S, Comi P, Giglioni B, Tolstoshev P, Lanyon WG, Mitchell GJ, et al. Delta-beta-thalassemia is due to a gene deletion. Cell 1976;9:71-80.  Back to cited text no. 10
Carrocini GC, Ondei LS, Zamaro PJ, Bonini-Domingos CR. Evaluation of HPFH and δβ-thalassemia mutations in a Brazilian group with high Hb F levels. Genet Mol Res 2011;10:3213-9.  Back to cited text no. 11
Verma S, Bhargava M, Mittal S, Gupta R. Homozygous delta-beta thalassemia in a child: A rare cause of elevated fetal hemoglobin. Iran J Ped Hematol Oncol 2013;3:222-7.  Back to cited text no. 12
Ramot B, Ben-Bassat I, Gafni D, Zaanoon R. A family with three beta-delta-thalassemia homozygotes. Blood 1970;35:158-65.  Back to cited text no. 13
Velasco-Rodríguez D, Alonso-Domínguez JM, González-Fernández FA, Villarrubia J, Ropero P, Martínez-Nieto J, et al. δβ-Thalassemia trait: how can we discriminate it from β-thalassemia trait and iron deficiency anemia? Am J Clin Pathol 2014;142:567-73.  Back to cited text no. 14


  [Figure 1], [Figure 2]

  [Table 1]


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