Genetic Studies by Sanger

Beta-thalassemia and Sickle Cell Anemia (HBB) (Code 20052)

Sickle Cell Anemia (SCA), a severe variant of Sickle Cell Disease (SCD), is a genetic disorder that results in severe anemia, an increased risk of bacterial infections, and blockages in the blood vessels. This condition affects red blood cells, causing problems in their shape and flexibility, an this is what leads to blockages in the blood vessels.

This form of SCD, caused by a homozygous mutation in the hemoglobin B gene (HBB) (rs334) that produces sickle hemoglobin (HbS), manifests after 3 months of life (before that, there are elevated levels of fetal hemoglobin) and can lead to complications such as severe anemia, infections, and painful blood vessel blockages in areas such as the abdomen, chest, or skeleton. Over time, these vaso-occlusive events can affect the function of organs and tissues.

Under conditions of hypoxia, HbS polymerizes, altering the shape and function of red blood cells, triggering a cascade of events resulting in hemolysis and vascular occlusion, reduced availability of nitric oxide, and endothelial damage. There are also other forms of SCA that result from compound heterozygosity of the HbS gene with other variants of hemoglobin B.

Diagnosis is based on specific hemoglobin tests, molecular genetic analysis, and genetic screening for prevention. The inheritance of this condition follows an autosomal recessive pattern, meaning that carrier couples have a 25% chance of having an affected child in each pregnancy.

Care from birth involves infection prevention, pain management, and multidisciplinary support in specialized centers. Treatments such as hydroxyurea, transfusions, and, in severe cases, bone marrow transplantation are available options. Other therapies, including L-glutamine, crizanlizumab, and voxelotor, are being evaluated in clinical trials.

The prognosis is variable and difficult to predict, with risks of acute infections and other serious complications (splenic sequestration, severe vaso-occlusive events, vital organ failure) that can be fatal.