Sickle cell disease is a group of disorders that affects hemoglobin,
the molecule in red blood cells that delivers oxygen to cells throughout
the body. People with this disorder have atypical hemoglobin molecules
called hemoglobin S, which can distort red blood cells into a sickle,
or crescent, shape.
Symptoms
Signs and symptoms of sickle cell disease usually begin in early childhood. The presence of fetal hemoglobin means that the disease doesn't manifest until after 3 months.
Characteristic features of this disorder include a low number of red blood cells (anemia), repeated infections, and periodic episodes of pain.
The severity of symptoms varies from person to person. Some people have mild symptoms, while others are frequently hospitalized for more serious complications.
The signs and symptoms of sickle cell disease are caused by the sickling of red blood cells. When red blood cells sickle, they break down prematurely, which can lead to anemia. Anemia can cause shortness of breath, fatigue, and delayed growth and development in children.
Figure A shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin.
Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood vessel. The inset image shows a cross-section of a sickle cell with abnormal (sickle) hemoglobin forming abnormal strands.
The rapid breakdown of red blood cells may also cause yellowing of the eyes and skin, which are signs of jaundice.
Painful episodes can occur when sickled red blood cells, which are stiff and inflexible, get stuck in small blood vessels. It causes hyperalgic focal ischemia (and sometimes infarction) when it occur in the muscles or skeleton. Over the course of time, VOAs may compromise the integrity of tissues or organs.
These episodes deprive tissues and organs of oxygen-rich blood and can lead to organ damage, especially in the lungs, kidneys, spleen, and brain. A particularly serious complication of sickle cell disease is high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Pulmonary hypertension occurs in about one-third of adults with sickle cell disease and can lead to heart failure.
Symptoms
Signs and symptoms of sickle cell disease usually begin in early childhood. The presence of fetal hemoglobin means that the disease doesn't manifest until after 3 months.
Characteristic features of this disorder include a low number of red blood cells (anemia), repeated infections, and periodic episodes of pain.
The severity of symptoms varies from person to person. Some people have mild symptoms, while others are frequently hospitalized for more serious complications.
The signs and symptoms of sickle cell disease are caused by the sickling of red blood cells. When red blood cells sickle, they break down prematurely, which can lead to anemia. Anemia can cause shortness of breath, fatigue, and delayed growth and development in children.
Figure A shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin.
Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood vessel. The inset image shows a cross-section of a sickle cell with abnormal (sickle) hemoglobin forming abnormal strands.
The rapid breakdown of red blood cells may also cause yellowing of the eyes and skin, which are signs of jaundice.
Painful episodes can occur when sickled red blood cells, which are stiff and inflexible, get stuck in small blood vessels. It causes hyperalgic focal ischemia (and sometimes infarction) when it occur in the muscles or skeleton. Over the course of time, VOAs may compromise the integrity of tissues or organs.
These episodes deprive tissues and organs of oxygen-rich blood and can lead to organ damage, especially in the lungs, kidneys, spleen, and brain. A particularly serious complication of sickle cell disease is high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Pulmonary hypertension occurs in about one-third of adults with sickle cell disease and can lead to heart failure.
How common is sickle cell disease?
Sickle cell disease affects millions of people worldwide. It is most
common among people whose ancestors come from Africa; Mediterranean
countries such as Greece, Turkey, and Italy; the Arabian Peninsula;
India; and Spanish-speaking regions in South America, Central America,
and parts of the Caribbean.
Sickle cell disease is the most common inherited blood disorder in the United States, affecting 70,000 to 80,000 Americans. The disease is estimated to occur in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans.
The frequency of sickle cell carriers in 25 European states is estimated at about 1/150. In central and western Africa (15-25%), in the French West Indies (10-15%) and in Mediterranean areas (1-15%) a high prevalence is observed in areas that are or have been affected by malaria, because the trait offers protection against pernicious malaria.
Sickle cell disease is the most common inherited blood disorder in the United States, affecting 70,000 to 80,000 Americans. The disease is estimated to occur in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans.
The frequency of sickle cell carriers in 25 European states is estimated at about 1/150. In central and western Africa (15-25%), in the French West Indies (10-15%) and in Mediterranean areas (1-15%) a high prevalence is observed in areas that are or have been affected by malaria, because the trait offers protection against pernicious malaria.
What genes are related to sickle cell disease?
Transmission is autosomal recessive.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.
Prenatal diagnosis
Prenatal diagnosis is possible, after genetic counseling, by molecular analysis of a sample of chorionic villi or amniotic fluid.
Management
From birth, management should integrate prevention of infections, pain and eventual complications, with social and psycho-educational support, within multidisciplinary centers that are equipped with intensive care (immediate access to blood transfusion).
An orphan drug based on hydroxycarbamide (hydroxyurea) has obtained European marketing authorization for the severe forms of the disease. Regular or occasional transfusions remain an essential therapeutic method.
Bone marrow transplantation is indicated in cases with cerebral vasculopathy.
Prognosis
The prognosis is difficult to predict. Serious VOA or organ failure can be a cause of death.