Journal of Dr. NTR University of Health Sciences

CASE REPORT
Year
: 2015  |  Volume : 4  |  Issue : 4  |  Page : 266--268

Double heterozygous HbQ India/HbD Punjab hemoglobinopathy: A rare case report


Sujani C Madabhushi1, Uma Swarup Nugoori2, Kiran Kumar Doppalapudi2, Mukesh Agrawal3,  
1 Department of Hematology, Vimta Labs Limited, Hyderabad, Telangana, India
2 Department of Biochemistry, Vimta Labs Limited, Hyderabad, Telangana, India
3 Lab Director, Clinical Reference Laboratory, Vimta Labs Limited, Hyderabad, Telangana, India

Correspondence Address:
Sujani C Madabhushi
Department of Hematology, Vimta Labs Limited, 142, IDA, Phase II, Cherlapally, Hyderabad - 500 051, Telangana
India

Abstract

Hemoglobinopathies constitute the most common genetic diseases in the world. In India, both beta-thalassemia and structural hemoglobin variants, such as hemoglobin S (HbS), hemoglobin D (HbD), and hemoglobin E (HbE), are common and pose significant health problem, these variants show heterozygous state along with beta-thalassemia. Compound heterozygosity among hemoglobin variants is very rare. Cation-exchange high-performance liquid chromatography (CE HPLC) provides accurate and reliable diagnosis of various hemoglobin variants. Here, we report an index case of double heterozygous hemoglobinopathy, hemoglobin Q (HbQ) India/HbD Punjab (ααQ India-ββD Punjab) using CE HPLC. This is the fifth report of double heterozygosity for HbQ India/HbD Punjab globally and fourth case report from India to the best of our knowledge.



How to cite this article:
Madabhushi SC, Nugoori US, Doppalapudi KK, Agrawal M. Double heterozygous HbQ India/HbD Punjab hemoglobinopathy: A rare case report.J NTR Univ Health Sci 2015;4:266-268


How to cite this URL:
Madabhushi SC, Nugoori US, Doppalapudi KK, Agrawal M. Double heterozygous HbQ India/HbD Punjab hemoglobinopathy: A rare case report. J NTR Univ Health Sci [serial online] 2015 [cited 2021 Jan 18 ];4:266-268
Available from: https://www.jdrntruhs.org/text.asp?2015/4/4/266/171745


Full Text

 INTRODUCTION



Hemoglobinopathy resulting from mutations in the α/β globin genes is one of the common genetic disorders. It is estimated that 7% of the world's population are carriers, making hemoglobinopathies the commonest monogenic disorder. The spectrum of inherited abnormalities in hemoglobin synthesis ranges from thalassemia to structurally defect hemoglobin variant. Hemoglobin variants arise from mutations in single amino acid sequence either in α or β globin chains, whereas thalassemias are due to decrease in globin chain production. [1] Most of the hemoglobin variants do not show any clinical symptoms in heterozygous state. A change in the amino acid sequence in both α and β chains called double heterozygosity in the same individual is very rare. Here we report a very rare double heterozygous hemoglobinopathy, hemoglobin Q (HbQ) India/hemoglobin D (HbD) Punjab (ααQ India-ββD Punjab).

 CASE REPORT



A 43-year-old Indian female belonging to Haryana state was evaluated for frequent history of pregnancy loss. In view of the history, as a part of investigation, a whole blood ethylenediaminetetraacetic acid, serum, and 3.2% sodium citrate plasma samples were sent for complete blood count, toxoplasmosis, rubella, cytomegalovirus and herpes (ToRCH) profile, lupus anticoagulant screen and confirm, anticardiolipin antibodies [immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM)], antiphospholipid antibodies (IgG and IgM), prothrombin time (PT), activated partial thromboplastin time (aPTT), and Mycobacterium tuberculosis (MTb).

As per as the request from referring physician, the patient was investigated for hemoglobinopathy disorder using cation-exchange high-performance liquid chromatography (CE HPLC) (Bio-Rad Variant-I, beta-thalassemia short program. Also agarose gel electrophoresis was carried out at pH 8.9. Routine hematological examination was carried out using automated cell counter, Beckman Coulter LH750.

ToRCH profile, lupus anticoagulant screen and confirm anticardiolipin antibodies (IgA, IgG, and IgM), antiphospholipid antibodies (IgG and IgM), PT, aPTT, and MTb all were normal except for cation-exchange HPLC, which showed four distinct peaks that were identified based on HPLC retention times depicted in the variant library of abnormal hemoglobins. Hemoglobin A (HbA) (α2β2) at the retention time of 2.52 min, followed by HbD Punjab (α2ββ Punjab) at 4.12 min, HbQ India (ααQβ2) at 4.74 min, and a peak in the hemoglobin C (HbC) window representing the hybrid of HbQ India/HbD Punjab at 4.96 min [Figure 1]a.{Figure 1}

Agarose gel electrophoresis at pH (8.9) showed three bands in A, S, and C positions and was interpreted as HbA at the position A, HbD at the S/D position, and HbQ/HbD in the position C.

Hemoglobin value and red blood cell indices of the index case were unremarkable [Table 1].{Table 1}

Peripheral smear examination showed normocytic normochromic blood picture with reticulocyte count of 1.3%. Sickling test was also performed that was negative.

Spouse sample was also tested separately for hemoglobinopathy if present any as a part of family screening, and the chromatogram was showing normal pattern [Figure 1]b. The index case lost both her parents at very early age, hence parenteral screening could not be performed.

 DISCUSSION



HbQ India is a rare α chain hemoglobin structural variant caused by a mutation on the cod on 64 of alpha-1 globin gene (AAG-GAG).The prevalence of HbQ India is 0.4% in India and is commonly found in Sindhi ethnicity. [2]

HbD Punjab (also called as HbD Los Angeles) is a β chain variant caused by point mutation on codon 121 (GAA-CAA) resulting in replacement of glutamic acid to glutamine. HbD Punjab is found greatest frequency of about 2% among the Sikhs in Punjab, India, as well as in nearby Gujarat (1%) and in Iran. In Heterozygous state it is clinically silent. [3] HbD Punjab is the fourth most frequently occurring hemoglobin variant in the world. [4]

An amalgam of clinical history along with hematological parameters and confirmation of the hemoglobin variant by both HPLC and alkaline electrophoresis is necessary.

On alkaline electrophoresis, differentiation of HbD Punjab and HbQ India based on electrophoretic mobility is difficult during routine screening. [5]

First report of HbQ India/HbD Punjab double heterozygous was reported by Higgins et al. in the year 2012, where they have observed four major peaks HbA, HbD Punjab, HbQ India, and HbQ India/HbD Punjab hybrid. [6] The findings observed on high-performance liquid chromatography (HPLC) in the present case are consistent with previously reported cases of double heterozygous for HbQ India/HbD Punjab. [7],[8]

In the present case, the cause for frequent history of pregnancy loss is obscure, and association of double heterozygous HbQ India/HbD Punjab to the clinical status of the patient cannot be attributed.

Previous four reports suggest that the individuals were of Indian origin, which indicates that even though this is rare abnormality but might be prevalent in Indian community due to high prevalence of HbD and HbQ cases. Such findings may cause diagnostic dilemmas. Documentation of these cases may help in antenatal counseling. Uncommon double heterozygosity states may increase in the near future particularly in places with confluent sociocultural and ethnic backgrounds. A mass screening for detection and counseling to prevent further spread of these genes in community is required.

Financial support and sponsorship

Nil.

Conflictst of interest

There are no conflicts of interest.

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