HbS

HbS, or hemoglobin S, is a variant of adult hemoglobin caused by a single amino acid substitution in the beta-globin chain of hemoglobin. The mutation replaces glutamic acid with valine at position 6 (Glu6Val) in the beta-globin gene (HBB). Under deoxygenated conditions, HbS tends to polymerize, causing red blood cells to assume a crescent shape, become less deformable, and rupture more easily. This sickling can obstruct microvasculature and lead to various complications.

Genetics and inheritance follow an autosomal recessive pattern. Individuals with two HbS alleles (HbSS) have sickle cell disease, while those with one HbS allele and one normal allele (HbAS) have sickle cell trait. Carriers have some protection against severe malaria in endemic regions.

Pathophysiology involves polymerization of deoxygenated HbS, leading to vaso-occlusion, ischemia, and chronic hemolysis. Recurrent vaso-occlusive events cause pain and organ injury; hemolysis contributes to anemia and vascular dysfunction. Splenic sequestration and eventual autosplenectomy increase susceptibility to infections from encapsulated bacteria.

Clinical features commonly include painful vaso-occlusive crises, acute chest syndrome, stroke risk, splenic complications, as well as growth and organ function impacts. Infections, particularly in children, are a major concern due to functional asplenia and immune dysfunction.

Diagnosis relies on newborn screening and hemoglobin typing by electrophoresis or high-performance liquid chromatography, which identifies HbS and quantifies its proportion. Management emphasizes pain control, hydration, vaccination, and infection prevention. Disease-modifying therapies include hydroxyurea to increase fetal hemoglobin, chronic transfusion for selected complications, and, in suitable cases, hematopoietic stem cell transplantation. Preventive care and lifestyle measures are essential, with supportive care remaining central to long-term outcomes.

Historically, sickle cell disease was described in the early 20th century, with the molecular basis clarified in the mid-20th century, revealing the Glu6Val substitution as the cause of HbS. The condition remains most prevalent in populations with a history of malaria exposure.