Sickle cell disease (SCD) is a group of inherited blood disorders that affect hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. The presence of an abnormal hemoglobin, Hemoglobin S (HbS), causes red blood cells to stiffen and form a characteristic crescent or sickle shape under certain conditions. This article specifically focuses on a form known as Sickle Cell Disease Type 2, which is more commonly referred to as Hemoglobin SC disease, or HbSC. This particular genotype is the second most common form of SCD, after the more severe Sickle Cell Anemia (HbSS).
Genetic Definition and Inheritance
HbSC disease is a compound heterozygous condition, meaning an individual has inherited two different abnormal beta-globin genes. A person with HbSC disease inherits one gene that codes for sickle hemoglobin (HbS) and a second gene that codes for Hemoglobin C (HbC). Both are variants of the HBB gene, which provides instructions for making the beta-globin chain of hemoglobin. The HbS gene results from a point mutation causing a change from glutamic acid to valine, while the HbC mutation causes a change from glutamic acid to lysine.
This disease follows an autosomal recessive pattern of inheritance, requiring the child to receive one affected gene from each parent. Typically, one parent is a carrier of the sickle cell trait (HbAS) and the other is a carrier of the Hemoglobin C trait (HbAC). This combination results in a mixture of abnormal hemoglobins in the red blood cells, generally consisting of about 50% HbS and 50% HbC.
The most common and severe form of the disease, Sickle Cell Anemia (HbSS), results from inheriting two copies of the HbS gene. The presence of both HbS and HbC in HbSC patients leads to a different clinical course than the HbSS form. Although the HbC variant is less prone to sickling than HbS, it causes red blood cells to lose water. This dehydration increases the concentration of HbS inside the cell and promotes polymerization and sickling.
Clinical Presentation and Disease Severity
HbSC disease is often described as having moderate severity, usually less intense than HbSS, yet it can still lead to significant health complications. Patients with HbSC typically maintain higher average hemoglobin levels (around 10 to 11 g/dL) compared to HbSS. This difference means that chronic anemia and its resulting physical consequences are generally less pronounced.
Despite this, the disease still causes the hallmark feature of SCD: vaso-occlusive crises (VOCs). These are episodes of intense pain caused by sickled cells blocking blood flow in small vessels. The frequency and severity of these pain crises are highly variable among individuals with HbSC, and the unique composition of HbSC leads to specific risks.
HbSC tends to cause a higher frequency of certain complications, such as proliferative retinopathy (affecting the blood vessels of the eye). Damage to the bones, particularly avascular necrosis of the hip joint (where bone tissue dies due to poor blood supply), is also common. While acute chest syndrome and pulmonary embolism are more frequent in HbSS, they still represent serious, life-threatening complications in HbSC patients. Regular monitoring is necessary, as the disease’s overall impact can be severe, particularly concerning organ damage affecting the spleen and lungs.
Diagnostic Testing and Monitoring
Identification of HbSC disease typically begins with universal newborn screening programs, often performed via a heel stick blood test. Once a potential hemoglobin disorder is detected, confirmatory testing is necessary to determine the exact genotype. Confirmation involves specialized laboratory techniques that separate and identify the different types of hemoglobin present.
These techniques include Hemoglobin Electrophoresis and High-Performance Liquid Chromatography (HPLC), which accurately quantify the percentages of HbS and HbC. The diagnosis is confirmed by the presence of roughly equal amounts of Hemoglobin S and Hemoglobin C, with little or no normal Hemoglobin A. This precise measurement is essential for distinguishing HbSC from other types of sickle cell disease or from sickle cell trait.
Once a diagnosis is established, ongoing monitoring tracks disease progression and prevents complications. This surveillance includes routine blood work, such as a complete blood count (CBC), to monitor anemia and other blood markers. Specialized screening for specific complications, such as annual comprehensive eye exams to detect retinopathy and imaging scans for avascular necrosis, is also standard care.
Current Management Approaches
Management of HbSC disease focuses on preventing complications, reducing the frequency of pain crises, and providing supportive care. Simple preventative measures include ensuring adequate hydration and avoiding triggers like extreme temperatures, high altitudes, and intense physical exertion that can precipitate a crisis. Prompt and effective pain management is crucial when vaso-occlusive crises occur, often involving both over-the-counter and prescription pain relievers.
Specific drug therapies are tailored to the individual’s disease severity and pattern of complications. Hydroxyurea, a medication that increases the production of fetal hemoglobin (HbF), reduces the frequency of pain crises and is used in many cases. Newer medications, such as L-glutamine, voxelotor, and crizanlizumab, offer additional options for reducing complications by targeting different aspects of the sickling process.
Preventing infection is a major focus, as individuals with SCD are at a higher risk due to spleen dysfunction. This requires a strict schedule of routine vaccinations and, for young children, prophylactic antibiotics like penicillin to prevent serious bacterial infections. In severe cases or during certain complications, blood transfusions may be used to temporarily reduce the concentration of sickled cells and improve oxygen-carrying capacity.