INTRODUCTION

Sickle Cell Disease is a group of blood disorders that causes red blood cells (RBCs) to become sickle-shaped, misshapen and break down. The oxygen-carrying capacity of such misshapen RBCs reduce significantly. Sickle cell anemia is an inherited red blood cell disorder in which there aren't enough healthy red blood cells to carry oxygen throughout your body. It is a genetically transferred disease. Red Blood Cells contain a protein called hemoglobin. This is the protein that binds oxygen and carry it to all the parts of the body.

A gene on chromosome 11 is responsible for producing hemoglobin protein. This gene sometimes becomes abnormal due to mutation. If a person inherits two abnormal copies of this gene, one from each parent, then that person will develop sickle cell disease. The sickle cell gene is passed from generation to generation in a pattern of inheritance called autosomal recessive inheritance. This means that both the mother and the father must pass on the defective form of the gene for a child to be affected. There's no cure for most people with sickle cell anemia. But treatments can relieve pain and help prevent complications associated with the disease.

TYPES OF SCD

Following are the most common types of SCD:

HbSS

People who have this form of SCD inherit two sickle cell genes (S), one from each parent. This is commonly called sickle cell anemia and is usually the most severe form of the disease.

HbSC

People who have this form of SCD inherit a sickle cell gene (S) from one parent and from the other parent a gene for an abnormal hemoglobin called C. Hemoglobin is a protein that allows red blood cells to carry oxygen to all parts of the body. This is usually a milder form of SCD.

HbS beta thalassemia

People who have this form of SCD inherit one sickle cell gene (S) from one parent and one gene for beta thalassemia, another type of anemia, from the other parent. There are two types of beta thalassemia: 0 and +. Those with HbS beta 0-thalassemia usually have a severe form of SCD. People with HbS beta +-thalassemia tend to have a milder form of SCD.

There also are a few rare types of SCD:

HbSD, HbSE, and HbSO

People who have these forms of SCD inherit one sickle cell gene (S) and one gene from an abnormal type of hemoglobin (D, E, or O). Hemoglobin is a protein that allows red blood cells to carry oxygen to all parts of the body. The severity of these rarer types of SCD varies.

SICKLE CELL TRAIT (SCT)

HbAS

People who have SCT inherit one sickle cell gene (S) from one parent and one normal gene (A) from the other parent. This is called sickle cell trait (SCT). People with SCT usually do not have any of the signs of the disease and live a normal life, but they can pass the trait on to their children. Additionally, there are a few, uncommon health problems that may potentially be related to sickle cell trait.

SYMPTOMS

Signs and symptoms of sickle cell anemia usually appear around 5 months of age. They vary from person to person and change over time. Signs and symptoms can include:

         Anemia. Sickle cells break apart easily and die, leaving you with too few red blood cells. Red blood cells usually live for about 120 days before they need to be replaced. But sickle cells usually die in 10 to 20 days, leaving a shortage of red blood cells (anemia).

Without enough red blood cells, your body can't get enough oxygen, causing fatigue.

         Episodes of pain. Periodic episodes of pain, called pain crises, are a major symptom of sickle cell anemia. Pain develops when sickle-shaped red blood cells block blood flow through tiny blood vessels to your chest, abdomen and joints. Pain can also occur in your bones.

The pain varies in intensity and can last for a few hours to a few weeks. Some people have only a few pain crises a year. Others have a dozen or more pain crises a year. A severe pain crisis requires a hospital stay.

Some adolescents and adults with sickle cell anemia also have chronic pain, which can result from bone and joint damage, ulcers, and other causes.

         Swelling of hands and feet. The swelling is caused by sickle-shaped red blood cells blocking blood flow to the hands and feet.

         Frequent infections. Sickle cells can damage your spleen, leaving you more vulnerable to infections. Doctors commonly give infants and children with sickle cell anemia vaccinations and antibiotics to prevent potentially life-threatening infections, such as pneumonia.

         Delayed growth or puberty. Red blood cells provide your body with the oxygen and nutrients needed for growth. A shortage of healthy red blood cells can slow growth in infants and children and delay puberty in teenagers.

         Vision problems. Tiny blood vessels that supply your eyes can become plugged with sickle cells. This can damage the retina the portion of the eye that processes visual images and lead to vision problems.

CAUSES

Mutations in the HBB gene cause sickle cell disease.

Hemoglobin consists of four protein subunits, typically, two subunits called alpha-globin and two subunits called beta-globin. The HBB gene provides instructions for making beta-globin. Various versions of beta-globin result from different mutations in the HBB gene. One particular HBB gene mutation produces an abnormal version of beta-globin known as hemoglobin S (HbS). Other mutations in the HBB gene lead to additional abnormal versions of beta-globin such as hemoglobin C (HbC) and hemoglobin E (HbE). HBB gene mutations can also result in an unusually low level of beta-globin; this abnormality is called beta thalassemia.

In people with sickle cell disease, at least one of the beta-globin subunits in hemoglobin is replaced with hemoglobin S. In sickle cell anemia, which is a common form of sickle cell disease, hemoglobin S replaces both beta-globin subunits in hemoglobin. In other types of sickle cell disease, just one beta-globin subunit in hemoglobin is replaced with hemoglobin S. The other beta-globin subunit is replaced with a different abnormal variant, such as hemoglobin C. For example, people with sickle-hemoglobin C (HbSC) disease have hemoglobin molecules with hemoglobin S and hemoglobin C instead of beta-globin. If mutations that produce hemoglobin S and beta thalassemia occur together, individuals have hemoglobin S-beta thalassemia (HbSBetaThal) disease.

Abnormal versions of beta-globin can distort red blood cells into a sickle shape. The sickle-shaped red blood cells die prematurely, which can lead to anemia. Sometimes the inflexible, sickle-shaped cells get stuck in small blood vessels and can cause serious medical complications.

DIAGNOSIS

SCD is diagnosed with a simple blood test. It most often is found at birth during routine newborn screening tests at the hospital. In addition, SCD can be diagnosed before birth.

Because children with SCD are at an increased risk of infection and other health problems, early diagnosis and treatment are important.

You can call your local sickle cell organization to find out how to get tested.

TREATMENT

Management of sickle cell anemia is usually aimed at avoiding pain episodes, relieving symptoms and preventing complications. Treatments might include medications and blood transfusions. For some children and teenagers, a stem cell transplant might cure the disease.

Medications

         Hydroxyurea (Droxia, Hydrea, Siklos). Daily hydroxyurea reduces the frequency of painful crises and might reduce the need for blood transfusions and hospitalizations. It can also increase your risk of infections. Don't take the drug if you're pregnant.

         L-glutamine oral powder (Endari). The FDA recently approved this drug for treatment of sickle cell anemia. It helps in reducing the frequency of pain crises.

         Crizanlizumab (Adakveo). The FDA recently approved this drug for treatment of sickle cell anemia. Given through a vein, it helps reduce the frequency of pain crises. Side effects can include nausea, joint pain, back pain and fever.

         Pain-relieving medications. Your doctor might prescribe narcotics to help relieve pain during sickle cell pain crises.

         Voxelotor (Oxbryta). The Food and Drug Administration (FDA) recently approved this oral drug to improve anemia in people with sickle cell disease. Side effects can include headache, nausea, diarrhea, fatigue, rash and fever.

Surgical and other procedures

         Blood transfusions. In a red blood cell transfusion, red blood cells are removed from a supply of donated blood, then given through a vein to a person with sickle cell anemia. This increases the number of normal red blood cells, which helps reduce symptoms and complications.

Risks include an immune response to the donor blood, which can make it hard to find future donors; infection; and excess iron buildup in your body. Because excess iron can damage your heart, liver and other organs, if you undergo regular transfusions, you might need treatment to reduce iron levels.

         Stem cell transplant. Also known as bone marrow transplant, this procedure involves replacing bone marrow affected by sickle cell anemia with healthy bone marrow from a donor. The procedure usually uses a matched donor, such as a sibling, who doesn't have sickle cell anemia.

Because of the risks associated with a bone marrow transplant, the procedure is recommended only for people, usually children, who have significant symptoms and complications of sickle cell anemia.

The procedure requires a long hospital stay. After the transplant, you'll receive drugs to help prevent rejection of the donated stem cells. Even so, your body might reject the transplant, leading to life-threatening complications.