Haemoglobinopathies in tribal populations of India.

Haemoglobinopathies particularly haemoglobin S and E (HbS, HbE) and β-thalassaemia are important challenges for tribal populations in India. The HbS, HbE and β-thalassaemia genes are variably distributed across various tribal populations of India. HbE is mainly restricted in tribals of North-East, West Bengal, Odisha and those in Andaman and Nicobar islands. HbS has more extensive distribution in the country (10-40% trait frequency) and the homozygotes and double heterozygotes present with a wide array of morbidities. the morbidity varies greatly in different areas of the country due to differential co-inheritance of α-thalassaemia gene and interaction of various epistatic and environmental factors. Though substantial data on prevalence of these disorders exist, there is an urgent need to develop integrated hierarchical core facilities to manage the disease. Such centres will generate more data and will also explore areas of management which need more local attention. Newborn screening, genetic counselling, carrier detection, prenatal diagnosis along with management of cases should form the basic infrastructure of haemoglobinopathy management. Research in this areas should continue focusing on various challenges in care delivery, prevention and basic sciences on interaction of haemoglobinopathies with various other infections.

HbA2 levels in normal, B-thalassaemia and haemoglobin E carriers by capillary electrophoresis

Objective: The capillary electrophoresis (CE) is a new system that utilizes the principle of electrokinetic separation of molecules in eight electrolyte buffer-fi lled silica capillaries. In this study, we established the normal ranges of haemoglobin A2 (HbA2) and haemoglobin F (HbF) levels for normal individuals using this system and also the HbA2 level in β thalassaemia and haemoglobin E (HbE) individuals. Materials and Methods: 154 samples from normal individuals, 218 samples from β thalassaemia heterozygotes and 91 samples from HbE heterozygotes were subjected to high performance liquid chromatography (HPLC) and CE analysis. Results: The normal ranges for HbA2 and HbF by CE were 2.75% (SD 0.26%) and 0.03% (SD 0.24%) respectively, which were signifi cantly lower than that of HPLC 2.88% (SD 0.25%) and 0.58% (SD 0.61%) (p <0.001). The HbA2 level for HbE heterozygotes was 3.58% (SD 0.44%), which was signifi cantly higher than normal (p <0.001) but lower than that of β-thalassaemia heterozygotes (p<0.001) and the true HbE level was 24.28% (SD 3.38%). Conclusion: The CE system provided a fully automated and high throughput system for haemoglobin analysis. We established the normal ranges for HbA2 and HbF levels by CE. We also determined the ranges for HbA2 in beta thalassaemia and HbE heterozygotes using this system.

Hb E/beta-thalassaemia: a common & clinically diverse disorder.

Haemoglobin E-beta thalassaemia (Hb E/β-thalassaemia) is the genotype responsible for approximately one-half of all severe beta-thalassaemia worldwide. The disorder is characterized by marked clinical variability, ranging from a mild and asymptomatic anaemia to a life-threatening disorder requiring transfusions from infancy. The phenotypic variability of Hb E/β-thalassaemia and the paucity of long-term clinical data, present challenges in providing definitive recommendations for the optimal management of patients. Genetic factors influencing the severity of this disorder include the type of beta-thalassaemia mutation, the co-inheritance of alpha-thalassaemia, and polymorphisms associated with increased production of foetal haemoglobin. Other factors, including a variable increase in serum erythropoietin in response to anaemia, previous or ongoing infection with malaria, previous splenectomy and other environmental influences, may be involved. The remarkable variation, and the instability, of the clinical phenotype of Hb E beta-thalassaemia suggests that careful tailoring of treatment is required for each patient, and that therapeutic approaches should be re-assessed over-time.

Salmonella Typhi and Plasmodium falciparum Co-infection in a 12-year Old Girl with Haemoglobin E Trait from a Non-malarious Area in Bangladesh.

A 12-year old girl from Uttar Badda, Dhaka, Bangladesh, was admitted to the Dhaka Hospital of ICDDR,B, with a 23-day history of fever and diarrhoea. After admission, she was treated for culture-proven Salmonella Typhi-associated infection and was discovered to be heterozygous for haemoglobin E. Despite treatment with appropriate antibiotics, the patient’s condition did not improve, prompting further investigation, which revealed malaria due to Plasmodium falciparum. Dhaka is considered a malaria-free zone, and the patient denied recent travel outside Dhaka. Subsequently, the patient recovered fully on antimalarial therapy.

Expression of Hb b-T and Hb b-E genes in Eastern India—Family studies.

The distribution patterns of different haemoglobins were observed amongst the family members of β-thalassaemia homozygous and HbE-β-thalassaemia patients with the aid of gel electrophoretic and alkali denaturation techniques. Of the 18 families studied, four belonged to β-thalassaemia homozygous and 14 to HbE-β-thalassaemia patients. Interaction of HbE and β-thalassaemia genes resulted in major clinical abnormalities with increase in the percentages of haemoglobins F and E. The percentages of HbA2 in homozygous β- thalassaemia were within the normal range. Although in Southeast Asia the β° type of HbEthalassaemia is more prevalent, only one individual with this type of thalassaemia was observed during this survey. In the rest of the patients examined the percentages of adult haemoglobin ranged from 5.2 to 42.5 indicating the presence of a b+ type gene.