Chapter 31: The Burden of the Sickle Cell Gene in India

Overview

The burden of sickle cell disease (SCD) in India is high. SCD is widespread not only among the indigenous populations but also among the scheduled castes and other backward classes. The sickle gene is linked to the Asian haplotype with high fetal hemoglobin (HbF) levels, but SCD patients have an extremely diverse clinical presentation in different regions of the country. The frequency of associated α thalassemia is variable in different populations, and this also modulates the severity of the disease. The main causes of morbidity are acute or chronic painful events, infections, and anemia. The spectrum of bacterial infections in Indian SCD patients is different from African cohorts; Staphylococcus aureus, Salmonella, Klebsiella, and Escherichia coli are more commonly seen. Fixed low-dose hydroxyurea therapy has been effective in Indian patients; however, compliance, availability of the drug, and accessibility are some of the constraints. The Gujarat SCD control program has served as a model for community screening using solubility test and high-performance liquid chromatography (HPLC) analysis followed by counseling and prenatal diagnosis in different states. Some challenges include limited awareness and late registration in antenatal clinics. Newborn screening programs have been introduced relatively recently in a few states, and follow-up of birth cohorts will help to understand the natural history of SCD in India. Curative options such as hematopoietic stem cell transplantation are not easily available to these economically disadvantaged populations due to the high cost and lack of suitable donors. Different government initiatives are also supporting care and control programs, and these should lead to a national registry of SCD patients in India.

Introduction

In India, the sickle cell gene was first reported among the hill tribes of northern Tamil Nadu in 1952.¹ There followed a debate as to whether there had been a single origin of the sickle cell mutation with subsequent migration into Equatorial Africa, Saudi Arabia, and India or whether there had been several independent occurrences of the sickle cell gene. Analyzing polymorphisms on the β-globin gene cluster surrounding the sickle hemoglobin (HbS) gene locus has discerned patterns believed to represent ancestral DNA structures upon which the HbS mutation has occurred relatively recently. These patterns are referred to as β-globin haplotypes, and there are at least 3 African haplotypes named after the areas where they were first described—the Benin, Senegal, and Bantu (or Central African Republic) haplotypes.² The β-globin gene flanking the HbS locus in eastern Saudi Arabia and in India has a different structure not seen in African populations and is believed to represent a fourth independent occurrence of the HbS mutation, the Arab-Indian or Asian haplotype.³ However, the most recent evidence using whole-genome sequencing data points to a single origin of the sickle allele approximately 7300 years ago during the Holocene Wet Phase or Green Sahara.⁴ The Asian haplotype associated with higher fetal hemoglobin levels and variable disease severity is now recognized ...