Glu6Val

Glu6Val refers to a specific missense mutation in the beta-globin chain of hemoglobin, in which the sixth amino acid, glutamic acid (Glu), is replaced by valine (Val). The change is encoded by a single nucleotide substitution in the HBB gene at codon 6 (GAG to GTG), giving rise to the abnormal hemoglobin variant known as hemoglobin S (HbS).

The Glu6Val substitution alters the properties of hemoglobin. Under low-oxygen conditions, HbS tends to polymerize, causing red blood cells to become rigid and sickle-shaped. These deformed cells are prone to hemolysis and can obstruct small blood vessels, leading to anemia, pain crises, tissue ischemia, and various organ complications.

Clinical presentation depends on zygosity. Individuals with two HbS alleles (homozygous HbSS) have sickle cell disease, characterized by recurrent pain episodes, chronic hemolytic anemia, and risk of organ damage. Individuals with one HbS allele (sickle cell trait, HbAS) usually have no or mild symptoms, but under extreme physiological stress they may experience complications and can pass the mutation to offspring.

The Glu6Val mutation is most common among populations with ancestry from malaria-endemic regions, where the heterozygote state offers some protection against Plasmodium falciparum. The allele is present at lower frequencies in parts of the Middle East, India, and the Mediterranean.

Diagnosis typically involves newborn screening, followed by confirmatory testing such as hemoglobin electrophoresis, high-performance liquid chromatography, or DNA analysis. Management ranges from supportive care and pain management to disease-modifying therapies (for example, hydroxyurea to increase fetal hemoglobin) and, in some cases, transfusion, stem cell transplantation, or gene therapy.