Sickle cell disease (SCD) is a group of rare blood disorders that result in sickled erythrocytes (red blood cells). Such cells have shorter lifespans and look like a sickle, which is a crescent-shaped farm tool, as opposed to the round disk shape of healthy red blood cells.
While the disease’s frequency varies by country, the disease has been found to be more common in people of African, Hispanic, Mediterranean, Middle Eastern, and Indian descent1.
Symptoms of sickle cell disease include severe infections, fatigue, jaundice, anemia, and pain in the bone, abdomen, and chest. Painful crises often occur when hard and sticky sickled red blood cells get stuck in small blood vessels, clogging blood flow2.
Sickle cell disease is a monogenic disorder where variants in the HBB (hemoglobin beta) gene cause SCD. The inheritance pattern is autosomal recessive, so both sickle cell genes must be inherited in order to be affected. If only one altered gene is inherited, the individual would be an unaffected carrier.
The HBB gene codes for beta-globin, which make up two of the four parts of hemoglobin. Mutations in the gene lead to abnormal versions of beta-globin, such as hemoglobin S (HbS) and hemoglobin C (HbC), or low levels of beta-globin, resulting in beta thalassemia1.
The most severe form of SCD, sickle cell anemia, is caused by inheriting the sickle hemoglobin (HbS) variant of the HBB gene from both parents. Other often less severe forms of sickle cell disease are caused by compound heterozygous genotypes; for example, sickle beta-zero thalassemia is caused by inheriting HbS, along with the hemoglobin beta zero thalassemia variant of the HBB gene.
Diagnosis is most often made through newborn screening3. If not through a simple blood test at the time of birth or later, other lab tests that measure levels of hemoglobin in the blood or genetic testing for mutations in the HBB gene can be conducted to diagnose SCD.
A study of 503 pediatric sickle cell disease patients published in 2019 showed that whole genome sequencing (WGS) is helpful in not only predicting disease progression but also gaining information on concomitant disease risk and drug metabolism4. In turn, such genomic insight could shape and personalize the treatment plans for patients to prevent or minimize organ damage.
Other methods of treatment are to avoid triggers of pain by staying warm and hydrated and taking deep breaths.
Millions are affected by sickle cell disease worldwide. With the different levels of severity and types of SCD, and the only available potential cure being bone marrow or stem cell transplant, it is important for patients to have access to various treatment options. In addition, as a study funded by Novartis and published in 2018 showed, WGS of 871 African American SCD patients was effective in further examining genetic modifiers of SCD, which is crucial in improving the personalization of SCD treatment7. Hopefully, more genomic research will help pave the way to more effective treatment of sickle cell disease.
- MedlinePlus Genetics. Sickle cell disease
- NORD. Sickle Cell Disease
- CDC. Sickle Cell Disease (SCD)
- Simoneaux, Richard. Whole Genome Sequencing of Pediatric Sickle Cell Disease Patients. Oncology Times 41 (3), 11-12 (2019).
- PubChem. Voxelotor
- Novartis. ADAKVEO
- Rampersaud, E., Palmer, L.E., Hankins, J.S.et al. Precision Medicine for Sickle Cell Disease through Whole Genome Sequencing.Blood 132 (Supplement 1): 3641 (2018).