Sickle cell disease (SCD) is a term that describes a group of inherited diseases that are an increasing global health concern. It is estimated that each year, 300,000 infants are born with sickle cell anemia and this figure will increase to 400,000 by 2050. Cases of the disease are high in sub-Saharan Africa, the Mediterranean, India and the Middle East. The presence of sickle cell disease overlaps with protection from malaria. SCD is the most common inherited disorder among those of African ancestry, as there is an estimated 100,000 people affected in the United States.
Mechanisms responsible for sickle cell disease
SCD is a group of conditions that impact hemoglobin, which is a molecule in red blood cells responsible for delivering oxygen to cells in the body. Normal red blood cells are disc-shaped and flexible so that they can move through blood vessels. The red blood cells of those affected appear atypically, with a distorted and crescent shape. Therefore, these red blood cells cannot move as easily through the blood vessels and can potentially block blood flow. Sickle cell disease occurs due to a single gene mutation in a gene that encodes a hemoglobin subunit. It is simply a substitution of one DNA base, which has a vast effect. As a result of the mutation, the amino acid coded for is changed, meaning the cell has a non-functional structure and cannot effectively carry out its typical functions.
Clinical presentation of sickle cell disease
Patients with SCD experience symptoms due to the sickling of their red blood cells. Red blood cells which have sickled can break down prematurely and cause anemia. In turn, patients can experience fatigue and shortness of breath, and in children, delayed growth and development can be observed.
The symptoms of sickle cell disease usually begin in early childhood, usually just after 6 months of age. Sickle cell disease is characterized as a lifelong disease that causes organ damage, severe pain, and haemolytic anemia. However, the severity of symptoms varies between patients and life expectancy shows high variability too. A frequent complication of SCD is stroke in adults with the condition. This can lead to physical and cognitive disability and can have a high mortality rate.
The impacts of sickle cell disease are widespread and affect many different systems including the: cardiothoracic system, nervous system, reticuloendothelial system, musculoskeletal system, urogenital system and gastrointestinal system. The impacts on these systems can result in organ failure and in many cases hospitalization and death. The most common cause of hospitalization in patients with sickle cell anemia is acute pain which often affects the extremities, chest and back. Specifically, pain is caused by vaso-occlusive crisis. This occurs when circulation is blocked by sickled red blood cells, which consequently causes damage to the organ being supplied with blood.
Treatment options for patients with sickle cell disease
Treatments have generally improved, and the current methods include hydroxycarbamide, erythrocyte transfusion and hematopoietic stem cell transplantation. The therapies alter the course of sickle cell disease and aim to improve the quality of life for sufferers.
One method of hematopoietic stem cell transplantation involves removing the stem cells in the bone marrow from patients with sickle cell disease and correcting the mutation in the hemoglobin gene. In a laboratory, the corrected stem cells have been shown to produce normal red blood cells without deformities. Whilst this is promising research, more investigation is needed before this can be widely used as a treatment. It is estimated that worldwide, almost 2,000 patients with sickle cell disease have undergone stem cell transplantation and survival exceeds 90%. However, there are risks with hematopoietic stem cell treatment as there are questions over the risk of infertility, infection, and other long-term complications.