Clinical heterogeneity of sickle cell disease in Indian subcontinent

Background: Sickle cell gene is common in various population groups in different parts of India. This makes sickle cell disease a common and clinically relevant symptomatic hemoglobinopathy in India. Clinical features of this disease are very variable. The current review with perspective was created by reviewing national and international literature. Materials and Methods: Literature search in PubMed and in Indian literature resources as well as the author’s own experience of this disease biology spanning over more than 35 years was used as the primary database. Sickle cell anemia, sickle cell disease, was used as the stem against the search terminologies such as Clinical heterogeneity, Population distribution in India, Molecular Mechanisms for severity, Mechanisms, and Blood transfusion. Original articles and review articles were given preference over individual case reports. Results: There were many studies on the relative prevalence of the disease in different parts of the country. The disease in general was milder compared to the Afro-Caribbean form of the disease. The disease in Nagpur and adjoining areas was more severe than that in Gujarat and adjoining Maharashtra. The sickle cell disease in the north east tea garden workers was also milder as also the disease seen in the Nilgiri hills of Tamil Nadu and Waynad district of Kerala. The clinical features looked into for severity are painful crisis, chest syndrome, necrosis of femoral heads, and stroke. Little data are available on the perinatal complications of the disease. The frequency and severity of the disease with the above-mentioned clinical presentations were lower in milder forms of disease and presented in relatively older age groups. High fetal hemoglobin and a deletional variety of alpha thal-mutation was associated with milder forms of the disease. Nutritional deficiency, degree of anemia, and coinheritance of beta thalassemia gene tend to minimize the severity. Splenomegaly was very common and often HbS beta thalassemia is misdiagnosed as sickle cell anemia. There are many ways by which the clinical presentation of Sickle cell disease (SCD) is seen but broadly interplay of vaso occlusion and hemolysis in different degrees and in different anatomical locations determines the clinical features and presentation of the condition. High ambient temperature and bad weather conditions also contribute toward differential clinical presentation of the disease and obviously occupation also plays a role. Priapism, pedal ulcers, and ocular manifestations of SCD are rarely reported. Conclusion: There is general consensus that there is clinical heterogeneity in the presentation of sickle cell disease in India both within and across population groups due to genetic and environmental background of the population. However, there are huge gaps in clinical information in this disease in different areas of the country and there are needs to initiate a large-scale population study related to clinical heterogeneity of the disease and correlate these presentations with genetic and environmental as well as nutritional status of the population. Most of the clinical presentation papers are often from hospital data and surely present more severely affected population. Chronic cardiovascular, renal, pulmonary, and hepatic conditions in various groups and in different age groups are poorly recorded.