Phenotypic variation in sickle cell disease: the role of beta globin haplotype, alpha thalassaemia and fetal haemoglobin in HbSS

Abstract

Introduction The haematological and clinical feature vary markedly between the different genotypes of sickle cell disease. Even within the single genotype of homozygous sickle cell disease (HbSS), there is marked variability which is presumed to result from interacting genetic and environmental factors. Areas Covered The classification of the different genotypes of sickle cell disease with approximate prevalence at birth in different communities and some of the major clinical and haematological differences. This assessment includes three potential genetic factors influencing haematology and clinical outcome in HbSS, the beta globin haplotype, alpha thalassaemia and persistence of fetal haemoglobin (HbF). Expert Opinion The author is a clinician with experience of sickle cell disease primarily in Jamaica but also in Greece, Uganda, Saudi Arabia and India. It is therefore necessarily an account of clinical data and does not address current debates on molecular mechanisms. Most data derive from Jamaica where efforts have been made to reduce any symptomatic bias by long term follow-up of patients all over the island and further reduced by a cohort study based on newborn screening which has been in operation for over 48 years.