Iron profile of pregnant sickle cell anemia patients in Odisha, India

ABSTRACT Introduction: During pregnancy, the iron requirement increases to meet the optimal growth of the fetus and prevent iron deficiency anemia-related complications in the mother. However, in sickle cell disease (SCD) primarily due to repeated blood transfusions and hemolysis-induced recycling of iron, its supplementation during pregnancy remains questionable and may be harmful. Methods: Twenty-five pregnant women with homozygous SCD and 25 pregnant women with normal hemoglobin variants were included as cases and control, respectively. Pregnancy and sickle cell anemia (SCA) were diagnosed using standard protocols. The serum iron, serum ferritin, total iron-binding capacity (TIBC), percentage transferrin saturation and C-reactive protein were estimated, as per the manufacturer's protocol. The complete blood count was performed. The unpaired 't-test' was performed using the SPSS v23.0 and the principal component analysis (PCA) was performed using the online software MetaboAnalyst for statistical analysis. Main Results: The studied cases had significantly lower mean hemoglobin and higher mean corpuscular volume (MCV), compared to controls. The mean serum-iron, serum-ferritin and percentage transferrin-saturation in the cases were significantly higher than that of the controls, while the TIBC was lower in the cases (p < 0.0001). The mean level of serum iron, ferritin, percentage transferrin saturation and TIBC were 309.44 ± 122.40mcg/dl, 860.36 ± 624.64ng/ml, 42.6 ± 17.30% and 241.32 ± 96.30 mcg/dl, respectively, in the cases and 95.36 ± 41.90mcg/dl, 122.28 ± 49.70ng/ml, 15.83 ± 3.10% and 492.6 ± 149.40mcg/dl in the controls, respectively. Higher MCV, mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with lower hemoglobin (Hb) were noted in the cases. The PCA revealed that the cases were more heterogeneous in terms of the variability of the iron status and hematological indices than the controls. Conclusion: The current study shows iron sufficiency in most cases of pregnancy with SCA and suggests that evaluation of iron status must be made before initiating iron prophylaxis in pregnant women with SCA, especially in regions having a high prevalence of sickle cell hemoglobinopathy.

Effect of α+ Thalassemia on the Severity of Plasmodium falciparum Malaria in Different Sickle Cell Genotypes in Indian Adults: A Hospital-Based Study.

There is a paucity of literature on the association of α+-thalassemia, sickle-cell hemoglobin disorders, and malaria in India. This study aimed to understand the effect of α+-thalassemia on the severity of Plasmodium falciparum malaria in adults with respect to sickle-cell genotypes. The study subjects were categorized into 'severe-malaria' and 'uncomplicated-malaria' and age-gender matched 'control' groups. Sickle-cell and α+-thalassemia were investigated in all the recruited subjects. The effect of α+-thalassemia on the severity of malaria was analyzed in HbAA and sickle-cell genotypes (HbAS and HbSS) separately. The prevalence of α+-thalassemia in various groups ranged from 41.5% to 81.8%. The prevalence of α+-thalassemia was lower (OR = 1.64; p = 0.0013) in severe malaria (41.5%) as compared to healthy controls (53.8%) with HbAA genotype. In contrast, in HbAS genotype, the prevalence of α+-thalassemia was higher (OR = 4.11; p = 0.0002) in severe malaria (81.8%) compared to controls (52.2%). In severe malaria with HbAA genotype, there was a significantly higher hemoglobin level and low MCV and MCH level in patients with α+-thalassemia compared to the normal α-globin genotype. Further, the incidence of cerebral malaria, hepatopathy, and mortality was lower in patients (HbAA) with α+-thalassemia as compared to normal α-globin genotype (HbAA). In severe malaria with either HbAS or HbSS genotype, only a few parameters showed statistical differences with respect to α+-thalassemia. Low prevalence of α+-thalassemia in severe malaria with HbAA genotype compared to healthy controls with HbAA genotype indicates the protective effect of α+-thalassemia against severe malaria. However, the high prevalence of α+-thalassemia in patients with HbAS genotype depicts its interference in the protective effect of sickle-cell against severe malaria.

Iron profile of pregnant sickle cell anemia patients in Odisha, India.

INTRODUCTION: During pregnancy, the iron requirement increases to meet the optimal growth of the fetus and prevent iron deficiency anemia-related complications in the mother. However, in sickle cell disease (SCD) primarily due to repeated blood transfusions and hemolysis-induced recycling of iron, its supplementation during pregnancy remains questionable and may be harmful. METHODS: Twenty-five pregnant women with homozygous SCD and 25 pregnant women with normal hemoglobin variants were included as cases and control, respectively. Pregnancy and sickle cell anemia (SCA) were diagnosed using standard protocols. The serum iron, serum ferritin, total iron-binding capacity (TIBC), percentage transferrin saturation and C-reactive protein were estimated, as per the manufacturer's protocol. The complete blood count was performed. The unpaired 't-test' was performed using the SPSS v23.0 and the principal component analysis (PCA) was performed using the online software MetaboAnalyst for statistical analysis. MAIN RESULTS: The studied cases had significantly lower mean hemoglobin and higher mean corpuscular volume (MCV), compared to controls. The mean serum-iron, serum-ferritin and percentage transferrin-saturation in the cases were significantly higher than that of the controls, while the TIBC was lower in the cases (p < 0.0001). The mean level of serum iron, ferritin, percentage transferrin saturation and TIBC were 309.44 ± 122.40mcg/dl, 860.36 ± 624.64ng/ml, 42.6 ± 17.30% and 241.32 ± 96.30 mcg/dl, respectively, in the cases and 95.36 ± 41.90mcg/dl, 122.28 ± 49.70ng/ml, 15.83 ± 3.10% and 492.6 ± 149.40mcg/dl in the controls, respectively. Higher MCV, mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with lower hemoglobin (Hb) were noted in the cases. The PCA revealed that the cases were more heterogeneous in terms of the variability of the iron status and hematological indices than the controls. CONCLUSION: The current study shows iron sufficiency in most cases of pregnancy with SCA and suggests that evaluation of iron status must be made before initiating iron prophylaxis in pregnant women with SCA, especially in regions having a high prevalence of sickle cell hemoglobinopathy.

Haptoglobin Genotypes Associated with Vaso-Occlusive Crisis in Sickle Cell Anemia Patients of Eastern India.

Sickle cell anemia is hallmarked by hemolysis, which releases hemoglobin (Hb) into the plasma promoting vaso-occlusive crisis (VOC). Haptoglobin (Hp) clears free Hb and decreases Hb-related pathophysiology in sickle cell anemia. There are two alleles (HP1 and HP2) and three genotypes (HP1-1, HP1-2 and HP2-2) of Hp with different frequencies in different populations. This study involved Hp level and genotype among normal and sickle cell anemia patients with varying severity of VOC. A total of 297 sickle cell anemia patients and 98 healthy controls were selected for the study. The sickle cell anemia patients were categorized as 'mild-phenotype' with no pain episodes and 'severe-phenotype' as having three or more acute pain episodes in the preceding 12 months. The Hp level was significantly lower (p < 0.001) in sickle cell patients anemia than controls; HP1-1 genotype had a higher Hp level compared to HP1-2 and HP2-2 (p < 0.05). Turkey-Kramer multiple comparison tests showed that mild and severe phenotypes have significant differences (p < 0.05) in Hb F%, Hb, platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct-bilirubin (Bil-D), total-bilirubin (Bil-T), lactate dehydrogenase (LDH) and Hp level. Pearson correlation revealed that Hp level has a positive (p < 0.05) correlation with Hb F%, Hb, packed cell volume (PCV) and serum urea; in contrast its level is negatively correlated with AST, ALT, Bil-T and LDH. A significantly higher frequency of HP2 allele and HP2-2 genotypes was found in severe phenotypes. In the studied population, it was found that higher HP2 frequency, low Hp level and more hemolysis favors the onset of VOC in sickle cell anemia.

Profiling of 35 Cases of Hb S/Hb E (HBB: c.20A>T/HBB: c.79G>a), Disease and Association with α-Thalassemia and ß-Globin Gene Cluster Haplotypes from Odisha, India.

Hb S/Hb E (HBB: c.20A>T/HBB: c.79G>A) is an uncommon variant of sickle cell disease resulting from coinheritance of Hb S and Hb E. Clinico-hematological and biochemical parameters of 35 cases of Hb S/Hb E disease were studied and compared with 70 matched cases of homozygous sickle cell disease (Hb SS) and Hb S/ß-thalassemia (ß-thal) with IVS-I-5 (G>C) (HBB: c.92+5G>C). The influence of α-thal and that of of ß-globin gene cluster haplotypes among Hb S/Hb E disease was also studied. Statistical analysis was done using GraphPad InStat version 3.06. Of the 35 cases, 20 (57.14%) had a moderate clinical presentation. Mean lactate dehydrogenase (LDH) level, vaso-occlusive crises (VOCs) per year, and annual blood transfusion requirements were significantly lower in Hb S/Hb E cases than in the other two groups. The hemoglobin (Hb) and packed cell volume (PCV) levels were significantly high in Hb S/Hb E cases with α-thal and these cases were associated with microcytic-hypochromic anemia. α-Thalassemia did not influence clinical presentation in Hb S/Hb E cases. The ß-globin gene cluster haplotypes of 70 alleles of Hb S/Hb E revealed an association of five typical haplotypes [Arab-Indian (A-I), Benin, Bantu, Cameroon and Senegal] in 95.71% cases. Hb S/Hb E disease exhibit asymptomatic to moderate phenotypic expression. However, further in-depth studies on Hb S/Hb E will help in reducing the disease burden especially in high-risk countries like India.

Association of plasma homocysteine level with vaso-occlusive crisis in sickle cell anemia patients of Odisha, India.

Vascular complications of sickle cell anemia (SCA) are influenced by many factors. Elevated plasma homocysteine (Hcy) is supposed to be an independent risk factor and is either genetic or nutritional origin. The present study evaluated the plasma Hcy level, MTHFR C677T gene polymorphism, effect of folic acid (FA) supplementation' and hemato-biochemical parameters in SCA and their effect on the vaso-occlusive crisis (VOC) in SCA patients of an Asian-Indian haplotype population. One hundred twenty cases of SCA (HbSS) and 50 controls with normal hemoglobin(HbAA) were studied. It was found that the plasma Hcy level is significantly higher (p < 0.0001) in patients with SCA (22.41 ± 7.8 µmol/L) compared to controls (13.2 ± 4.4 µmol/L). Moreover, patients without FA supplementation had a significantly (p < 0.001) higher Hcy level (27 ± 7 µmol/L) compared to those with supplementation (17.75 ± 5.7 µmol/L). Turkey-Kramer multiple comparison tests show that there is a significant difference (p < 0.05) in HbF percent, hemoglobin (Hb), platelet count, serum bilirubin (direct:Bil-D and total:Bil-T), aspartate transaminase (AST), lactate dehydrogenase (LDH), and plasma Hcy levels between mild and severe VOC. Between moderate VOC and severe VOC, there was a significant difference (p < 0.05) in HbF%, Bil-D, AST, Hcy. Pearson correlation revealed that plasma Hcy had a significantly (p < 0.05) positive correlation with AST, serum bilirubin (indirect and total), LDH, jaundice, stroke, VOC per year, and hospitalization per year whereas it was inversely correlated with HbF percentage, Hb level, and FA treatment. In the study population, increased plasma Hcy level, hemolysis, and platelet activation were found to influence VOC in SCA.

Erythrocyte cAMP in Determining Frequency of Acute Pain Episodes in Sickle Cell Disease Patients from Odisha State, India.

Vaso-occlusive crisis (VOC) occurs more frequently during stress in sickle cell disease patients. Epinephrine released during stress increases adhesion of sickled red blood cells (RBCs) to endothelium and to leukocytes, a process mediated through erythrocyte cyclic adenosine monophosphate (cAMP). Increased adhesion of sickled RBCs retards blood flow through the capillaries and promotes vaso-occlusion. Therefore, we examined the association of RBC-cAMP levels with frequency of acute pain episodes in sickle cell disease subjects. Using a case control study design, we measured RBC-cAMP levels, fetal hemoglobin (Hb F), α-thalassemia (α-thal) and other hematological parameters at baseline (sham treated) and after stimulation with epinephrine. The cases consisted of sickle cell disease subjects with three or more acute pain episodes in the last 12 months, and those without a single acute pain episode in the last 12 months were considered as controls. Significantly higher cAMP values were found in cases than the controls, in both sham treated (p < 0.001) and epinephrine treated RBCs (p < 0.001) by Wilcoxon Rank Sum test. However, significant association of cAMP values was observed both on univariate [odds ratio (OR): 4.8, 95% confidence interval (95% CI): 1.51-15.19, p < 0.008) and multivariate logistic regression analyses only in epinephrine treated (OR: 5.07, 95% CI: 1.53-16.82, p < 0.008) but not in sham-treated RBCs. In the covariates, Hb F consistently showed protective effects in univariate as well as in multivariate analyses. Frequent acute pain episodes are associated with higher cAMP levels than those with less frequent pain episodes, only after stimulation with epinephrine but not with baseline level.

Compound Heterozygote of Hb S (HBB: c.20A>T)/Hb Westdale (HBB: c.380_396delTGCAGGCTGCCTATCAG): Report of Four Cases from Odisha State, India.

We report four cases of compound heterozygotes for Hb S (HBB: c.20A>T) and a rare ß0-thalassemia (ß0-thal) mutation, Hb Westdale (HBB: c.380_396delTGCAGGCTGCCTATCAG), characterized by a 17 bp deletion between codons 126 to 131 in exon 3 of the ß-globin gene of human hemoglobin (Hb) confirmed by direct ß-globin gene sequencing. All four cases were from four unrelated families belonging to the Agharia caste, an endogamous ethnic community of the Sundargarh and Jharsuguda districts of Odisha State, India. Detailed observations indicated that all four cases of Hb S/Hb Westdale were clinically severe. On family screening, six family members were found to be heterozygous for Hb Westdale and were asymptomatic. Deletional α-thalassemia (α-thal) and XmnI polymorphism were studied for all the Hb Westdale cases. The Hb S/Hb Westdale cases had an early median age at onset of symptoms and presentation, more requirement of blood transfusions, splenomegaly and hepatomegaly and were found to be clinically more severe when compared with the Hb S-ß-thal with IVS-I-5 (G>C) (HBB: c.92 + 5G>C) cases. Overall, the findings indicate that this rare and hitherto unreported compound heterozygosity of Hb S/Hb Westdale is a clinically significant hemoglobinopathy and its finding in a large endogamous community of Odisha State, India will have important implication in the epidemiology and understanding of the clinical spectrum of sickle cell disease in Indian context and prenatal diagnosis.

Association of fetal hemoglobin level with frequency of acute pain episodes in sickle cell disease (HbS-only phenotype) patients.

BACKGROUND: Sickle cell disease (SCD) is a Mendelian single gene disorder with highly variable phenotypic expression. In the present study, we analyzed the influence of HbF, alpha thalassemia and other hematological indices to determine their association with acute pain episodes. METHOD: This case control study consisted of SCD subjects with HbS phenotype experiencing three or more acute pain episodes in last twelve months (cases) and without any episode of acute pain during last twelve months (controls). Hematological parameters, HbF, and presence of alpha thalassemia were assessed in all subjects. RESULTS: A statistically significant difference between HbF levels (P < 0.025, χ2 test) and alpha thalassemia (P < 0.008, χ2 test) was observed between controls and cases group. Univariate analysis indicated that increased HbF levels > 25% (OR: 0.37, 95% CI: 0.18-0.77, P < 0.008) and presence of alpha thalassemia (OR: 0.53, 95% CI: 0.33-0.85, P < 0.009) provided protection, while multivariate analysis revealed significant protection was attributable only by higher HbF levels (OR: 0.39, 95% CI: 0.17-0.88, P < 0.025). Significantly higher HbF levels were observed only in the 11-20 age group of cases in comparison to controls (Student's t-test, P < 0.001). CONCLUSION: Higher concentrations of HbF are associated with protection against frequent episodes of acute pain crisis in SCD patients.

Effect of Assorted Globin Haplotypes and α-Thalassemia on the Clinical Heterogeneity of Hb S-ß-Thalassemia.

Hemoglobinopathies and thalassemias are the most commonly encountered monogenic disorders of blood in humans, posing a major genetic and public health problem round the globe. Hb S (HBB: c.20A>T)-ß-thalassemia (ß-thal) is a compound aberrant heterozygosity with inconsistent phenotypic expression, which are poorly described and clinically mapped. Comprehensive genetic characterization of such a population is highly warranted for complete understanding of the clinical heterogeneity, disease prognosis and therapeutic management. In this study, Hb S-ß-thal (n = 60) patients, strictly defined by varying degrees of clinical presentations, were selected to evaluate their genotype-phenotype agreement. Furthermore, ß-globin (n = 120) and α-globin gene clusters (n = 60) were genetically characterized and statistically correlated with clinical terminologies to explain the clinical heterogeneity. Our results revealed the association of the Arab-Indian haplotypes with nine different frameworks of ß-thal together with the modulating role of α-thalassemia (α-thal). The study subjects, including carriers of ß-thal haplotype III [- - - - - - -] (8.0%), presented with varying severe patterns of clinical symptoms such as painful crisis, multiple infections and splenomegaly, as an outcome of significantly less Hb F and higher Hb S levels (p < 0.5). The study findings indicated that together with α-thal, ß-thal haplotypes and Hb F levels, may possibly provide a close justification to support the clinical heterogeneity in the study population.

Comparative study of clinical presentation and hematological indices in hospitalized sickle cell patients with severe Plasmodium falciparum malaria.

BACKGROUND: Sickle-cell-gene has a high frequency in malaria endemic regions. In India, though the prevalence of both sickle-cell-gene and malaria are high, no study has been carried out. This study aims to find out the possible differences in hematological and clinical parameters in severe falciparum malaria with respect to sickle cell genotypes. METHODS: Five hundred fourteen adults with severe falciparum malaria hospitalized in Department of Medicine, Veer Surendra Sai Institute of Medical Sciences and Research, Burla, between August, 2010 to December, 2014 were included and categorized on the basis of sickle cell genotypes. The hematological parameters were compared by one-way-analysis-of-variance and incidence of sub-phenotypes of severe malaria was compared by χ2 test across the groups. RESULTS: Patients with sickle cell anemia (HbSS) and severe falciparum malaria had lower hemoglobin level compared to patients with normal ß-globin genotype (HbAA) and sickle cell trait (HbAS). Most of the hematological parameters were homogeneous in patients with HbAA and HbAS and different from patients with HbSS. Incidence of acute renal failure was low (χ2, 9.91; p, 0.002) and jaundice was high (χ2, 5.20; p, 0.022) in patients with HbSS. No clinical difference was observed in patients with HbAA and HbAS. The mortality was low (χ2, 4.33; p, 0.037) and high (χ2, 10.48; p, 0.001) in patients with HbAS and HbSS respectively compared to patients with HbAA. CONCLUSION: Though sickle-cell-gene protects against falciparum infections, the hematological parameters and sub-phenotypes of severe malaria remain unchanged when the infection progresses to a severe form in patients with HbAA and HbAS. Presence of hemolytic anemia in patients with HbSS shows diverse hematological and clinical phenotypes as compared to others. High mortality in patients with HbSS emphasizes the need for a better preventive approach to save valuable lives.

Study of Seminal Fluid Parameters and Fertility of Male Sickle Cell Disease Patients and Potential Impact of Hydroxyurea Treatment.

INTRODUCTION: Male Sickle cell disease (SCD) patients often have moderate to severe hypogonadism resulting in abnormal seminal fluid parameters due to testicular dysfunction. Hydroxyurea (HU), the only drug found to be effective in preventing morbidity and mortality in sickle cell disease patients has been found to further aggravate the testicular dysfunction. MATERIAL AND METHODS: This was a prospective study done at a tertiary care hospital over 26 months between September 2011 to October 2013. 100 male sickle cell disease patients of age group 15 to 45 years were recruited in the study. We evaluated seminal fluid indices in all patients and the effect of hydroxyurea on seminal fluid parameters. Hydroxyurea was given at low dose of 10mg/kg/day orally to patients with frequent vaso-occlusive crisis and frequent need of blood transfusion. Seminal fluid analysis was done according to WHO criteria before starting hydroxyurea and every 3 months after initiation of hydroxyurea. Patients with abnormal seminal parameters before hydroxyurea therapy were not given hydroxyurea therapy. Patients with abnormal sperm parameters were subjected for FNAC of testis. In sickle cell disease patients with hydroxyurea therapy, who developed abnormal seminal fluid parameters, hydroxyurea was stopped for 3 months and seminal fluid parameters were re-evaluated. Patients who had recovery of seminal indices after hydroxyurea cessation were restarted with hydroxyurea therapy at low dose. RESULTS: Among Sickle cell disease patients without hydroxyurea therapy, 18% of patients developed oligospermia and 4% developed azoospermia. Among sickle cell disease patients with hydroxyurea therapy, 20% of patients developed oligospermia and 10% developed azoospermia. Seminal fluid parameters reverted back to normal after stoppage of hydroxyurea for 3 months in 73% of patients. CONCLUSIONS: Alteration of sperm parameters is seen in a significant number of sickle cell disease patients. Also, alterations of seminal fluid parameters are exacerbated by hydroxyurea treatment even with low dose. Therefore, treatment with hydroxyurea in adolescent and adult male sickle cell disease patients should be preceded by routine assessment of seminal fluid parameters and followed up regularly every 3 months for any change in seminal fluid parameters for evidence of hydroxyurea toxicity.

Association of CD40L gene polymorphism with severe Plasmodium falciparum malaria in Indian population.

BACKGROUND & OBJECTIVES: Many host genetic factors are associated with the disease severity and fatal outcome of falciparum malaria. CD40L gene has been found to be one of the most important factors associated with malaria in African countries. This study was aimed to investigate the possible association of CD40L gene polymorphism in severe falciparum malaria in Indian adults. METHODS: One hundred fifteen adult cases with severe falciparum malaria were included in the study. Two single- nucleotide polymorphisms (SNPs) of CD40L gene, CD40L-726(C/T) and CD40L+220(C/T) were investigated, and the possible association with different clinical sub-phenotypes of severe falciparum malaria were analyzed. RESULTS: Statistically no significant difference was observed in the incidence of CD40L-726C between the patients and control group. The incidence of CD40L+220C allele was found to be significantly higher (OR, 2.25; p = 0.03) in male patients compared to controls but no significant difference was observed in females. Haplotype data showed the susceptibility of -726T/+220C haplotype to severe malaria whereas -726C/+220T was associated with protection against severe malaria. CD40L+220C allele was associated with severe malarial anaemia in males (χ2 = 6.60; p = 0.01). INTERPRETATION & CONCLUSION: CD40L gene polymorphism was found to be associated with severe falciparum malaria in Indian population especially in severe malarial anaemia. CD40L may be considered as a factor of immunity in understanding the pathophysiology of falciparum malaria.

Hb Tianshui (HBB: C.119A > G) in Compound Heterozygosity with Hb S (HBB: C.20A > T) from Odisha, India.

We describe here a rare ß-globin gene variant, Hb Tianshui [ß39(C5)Glu→Arg; HBB: c.119A > G], detected during routine screening in Odisha, India. This is the second report of Hb Tianshui and the first to describe the cation exchange high performance liquid chromatography (HPLC) and DNA studies of two cases of this variant. Both cases had coinherited Hb S (HBB: c.20A > T) but none presented with typical symptoms of sickle cell disease. One of the cases was heterozygous for a common α-thalassemia (α-thal) allele (-α(3.7)) (rightward) (NG_000006.1: g.34164_37967del3804) and marginally raised Hb F percentage, while the other Hb S/Hb Tianshui case was completely benign and healthy. An atypical Asian Indian haplotype [+ - + - +] could be assigned to the Hb Tianshui variant. Hb Tianshui seems to mimic a few other Hb variants in cation exchange HPLC. However, we report two specific patterns in the chromatograms that are characteristic to Hb Tianshui. Combining an alkaline electrophoresis result with cation exchange HPLC at screening would be preferred to detect this rare variant, especially in regions with considerable frequency of Hb E [ß26(B8)Glu→Lys; HBB: c.79G > A] or Hb S.

First Report of Hb Limassol [ß8(A5)Lys→Asn; HBB: c.27G>C] from Odisha, India.

In this short report, we describe the clinical presentation of a rare hemoglobin (Hb) variant, Hb Limassol [ß8(A5)Lys→Asn; HBB: c.27G>C] with a faster electrophoretic mobility than Hb A and that elutes in the P3 window on cation exchange high performance liquid chromatography (HPLC). This sequence variation at codon 8 (AAG>AAC) of the HBB gene was found in the four heterozygous cases, all of whom were clinically asymptomatic.

Inheritance of Hereditary Persistence of Fetal Haemoglobin (HPFH) in a Family of Western Odisha, India.

Hereditary persistence of foetal haemoglobin (HPFH) is a rare inherited haemoglobin disorders in India. We encountered five cases of HPFH-3 in heterozygous condition in a single family of western Odisha, India. All the cases had raised % HbF (26.1±3.23%) with pancellular distribution of HbF in erythrocytes. There were no abnormalities found in the red cell indices. All the cases were asymptomatic till date with normal growth and development. Molecular confirmation of this haemoglobin disorders is important for control and prevention of haemoglobinopathies in this region.