Sickle cell disease, along with α-thalassemia, is the most common hemoglobinopathy in West and East Africa, Saudi Arabia, Iran, central India, and northern Malaysia. Similar to thalassemias, the geographic distribution of the disease largely coincides with the endemic areas of malaria. The predominant HbS (hemoglobin S) forms aggregates upon oxygen depletion (absence of oxygen), or in acidosis, causing the erythrocytes to lose plasticity and develop a sickle-like shape. HbS erythrocytes are largely resistant to malaria plasmodia, which explains a selection advantage and the frequency of heterozygous carriers in affected countries.
Sickle cells can clump together in the smaller blood vessels and thus lead to infarctions of various organs with sometimes severe pain attacks. Splenic infarctions are common, leading to fibrosis and shrinkage over a prolonged course. Due to the loss of function of the spleen, patients are at considerable risk of infection. In addition, the altered cells are increasingly intercepted and degraded in the liver and spleen, leading to chronic hemolytic anemia.
The first symptoms appear at the age of a few months when HbF is increasingly replaced by HbA0, which in affected individuals is replaced by HbS. Persistence of HbF or a high permanent HbF content (above 10%) has a protective effect, which is also used therapeutically by drugs that increase the HbF content of the blood. Transfusions are also administered. So far, causal therapy is only possible by bone marrow transplantation. Sickle cell disease follows an autosomal recessive mode of inheritance; therefore, symptoms occur only in homozygosity for HbS (homozygous sickle cell disease, HbSS) or in compound heterozygosity of HbS with β-thalassemia or other variants of β-globin. The molecular genetic cause of sickle cell disease is a pathogenic variant in the β-globin gene (HBB) that causes the amino acid glutamic acid at position 6 of the protein to be replaced by valine.
Hematological testing to detect sickle cell disease is part of newborn screening. Molecular genetic analysis can confirm the diagnosis in the child and also offers the possibility to determine the analgesic carrier of the parents to determine a (recurrence) risk for further common offspring.
Bender MA. Sickle Cell Disease. 2003 Sep 15 [Updated 2017 Aug 17]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019 / AWMF Leitlinie Sichezellkrankhet Registernummer 025 - 016