Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Sickle Cell Anemia (SA) [D57.0], [D57.3]

OMIM numbers: 603903, 141900 (HBB)

Dipl.-Biol. Birgit Busse, Dipl.-Biol. Wolfgang Rupprecht

Scientific Background

Sickle cell anemia, which is the most frequent hemoglobinopathy besides α-thalassemia, is especially prevalent in Western and Eastern Africa, Saudi Arabia, Iran, Central India and Northern Malaysia. Similar to the thalassemias, the geographic distribution of the disease is largely congruent with the endemic areas of malaria. The prevalent HbS (hemoglobin S) forms aggregates after release of oxygen, deficiency of oxygen or acidosis and causes the erythrocytes to lose plasticity and to acquire a sickle shape. HbS erythrocytes are to a large extent resistant to malaria plasmodia, which explains the selective advantage and the large number of heterozygous carriers within the affected countries. Sickle cells may clot in the smaller blood vessels and thus cause infarction of different organs, accompanied by intense pain. Splenic infarction is common and over a longer period of time may lead to fibrosis and shrinking. The non-functioning of the spleen increases the patients’ risk of infections significantly. In addition, sickle cells are increasingly removed and degraded by the liver and spleen. This results in chronic hemolytic anemia.

The first signs and symptoms already arise at the age of a few months when HbF is supposed to be increasingly substituted by HbA0. Instead, it is substituted by HbS in affected patients. Persistence of HbF or a consistently high HbF level (above 10%) has a protective effect. This is also used therapeutically by medication which increases the HbF levels in the blood. Furthermore, transfusions are administered. Currently, a causal therapy is only possible in the form of bone marrow transplantation. Sickle cell anemia follows an autosomal recessive inheritance pattern, which is why signs and symptoms only occur in the case of homozygosity for the HbS (homozygous sickle-cell disease, HbSS) or in the case of compound heterozygosity of HbS with β-thalassemia or other variants of the β-globin. The molecular genetic cause of sickle-cell anemia is a mutation in the β-globin gene (HBB), which causes the amino acid glutamine acid in position 6 of the protein to be substituted for valine.