Sickle cell nephropathy in children

Abstract

Sickle cell disease (SCD) is one of the most common genetic disorders in the United States, affecting 100,000 Americans and millions of people worldwide, primarily of African or Mediterranean descent [1]. SCD is inherited in an autosomal recessive fashion and is a group of hemoglobinopathies associated with chronic hemolytic anemia and vaso-occlusive complications. It is likely that sickle hemoglobin (HgbS) and other hemoglobin variants arose out of genetic selection due to the fact that being a carrier (heterozygote) for HgbS confers some resistance to malarial infection with a resultant survival advantage [2]. All forms of SCD are the result of mutations in the two β-globin genes. β-globin is a major component of adult hemoglobin and is part of a group of genes involved in oxygen transport. The most common form of SCD is homozygous SS disease. Other variants of SCD are the result of compound heterozygotes for HgbS and other β-globin variants, including SC as well as Sβ+ thalassemia and Sβ0 thalassemia. All individuals who are homozygous or compound heterozygous for HgbS exhibit clinical manifestations of SCD. However, there is significant variability in clinical severity, which is related to genotype. Patients with SS disease generally have the most severe phenotype followed by individuals with Sβ0 thalassemia. Individuals with SC and Sβ+ thalassemia tend to have milder clinical phenotypes.