Sickle Cell Disease

A Closer Look at Sickle Cell Disease

The different forms of sickle cell disease are determined by the genes inherited from the person's parents.

Someone who inherits a sickle cell gene from each parent has hemoglobin SS disease, also called sickle cell anemia.

A person can also inherit a sickle cell gene from one parent and a different kind of abnormal gene from the other and end up with a different form of sickle cell disease, such as hemoglobin SC disease or hemoglobin S beta thalassemia.

Someone who inherits only one sickle cell gene and a normal gene from the other parent will have the sickle cell trait, but not the disease. A blood test can determine whether someone has a form of sickle cell disease or carries the sickle cell trait.

People with sickle cell trait don't have sickle cell disease and usually don't exhibit signs of the disorder, but they can pass the gene for the disease to their children. Many people don't know they have sickle cell trait. When both parents have the sickle cell trait, there's a 25% chance that a child will have sickle cell disease. But when one parent is carrying the trait and the other actually has the disease, the odds increase to 50% that their child will inherit the disease.

Who Is Affected?

In the United States, hemoglobin SS disease (sickle cell anemia) affects mostly African Americans. However, forms of sickle cell disease may occur in people with different ethnic backgrounds, such as those whose ancestors came from Mediterranean countries (including Turkey, Greece, and Italy), East India, or Middle Eastern countries.

Causes of Sickle Cell Disease

Hemoglobin allows red blood cells to carry oxygen. It is made up of alpha chains and beta chains. A child with sickle cell disease has inherited two defective genes for the beta chain of hemoglobin.

The hemoglobin can take on an abnormal shape, distorting the shape of RBCs. The cells change from a normal round, doughnut shape to the elongated shape of a sickle, or the shape of the letter "C."

Unlike normal RBCs, which move easily through small blood vessels, sickle cells are stiff and pointed. They have a tendency to get stuck in narrow blood vessels and block the flow of blood. This can cause episodes of pain and can also lead to organ damage because the tissues aren't getting enough oxygen.

Sickle cells have a shorter-than-normal life span, which leads to anemia (low RBC count). A normal red blood cell lives for about 120 days in circulation, whereas a sickle cell lives for only 10 to 20 days.

Diagnosis

Sickle cell disease usually is diagnosed at birth with a blood test during routine newborn screening tests. If a child tests positive on the screening test, a second blood test (called a hemoglobin electrophoresis) should be performed to confirm the diagnosis.

Because kids with sickle cell disease are at an increased risk of infection and other health complications, early diagnosis and treatment to prevent problems is important. Currently, more than 40 states require newborn screening programs for sickle cell disease.

Signs and Symptoms

Symptoms of sickle cell disease vary, ranging from mild to severe, and may be less severe or different in kids who have inherited a sickle cell gene from one parent and a different abnormal hemoglobin gene from the other.

Most kids with sickle cell disease have some degree of anemia and might develop one or more of the following conditions and symptoms as part of the disorder:

Acute chest syndrome: Inflammation, infection, and occlusion of small vessels may cause this syndrome. Signs include chest pain, coughing, difficulty breathing, and fever.

Aplastic crisis: This is when the bone marrow temporarily slows its production of RBCs due to infection or another cause, resulting in a serious drop in RBCs and severe anemia. Signs include paleness, fatigue, and rapid pulse.

Hand-foot syndrome (also called dactylitis): This painful swelling of the hands and feet may be the first sign of sickle cell anemia in some infants.

Infection: Kids with sickle cell disease are at increased risk for certain bacterial infections. It's important to watch for fevers of 101ºF (38ºC) or higher, which could signal an infection. Children with sickle cell disease and fever should be seen by a doctor immediately.

Painful crises: These may occur in any part of the body and may be brought on by cold or dehydration. The pain may last a few hours, a few days, or sometimes much longer. Pain may be so severe that a child needs to be hospitalized.

Splenic sequestration crises: The spleen becomes enlarged by trapping (or "sequestering") the abnormal RBCs. This can lead to a serious and rapid drop in the red cell count (severe anemia). Early signs include paleness, weakness or fatigue, an enlarged spleen, and pain in the abdomen.

Stroke: Impaired blood flow in the brain can occur when the sickle-shaped cells block small blood vessels, which may lead to a stroke. Signs can include headache, seizures, weakness of the arms and legs, speech problems, a facial droop, or loss of consciousness.

Other possible complications include leg ulcers, bone or joint damage, gallstones, kidney damage, painful prolonged erections in males (priapism), eye damage, and delayed growth.

Treatment

Bone marrow transplant is the only known cure for sickle cell disease. Transplants are complex and risky procedures and currently are an option only for a carefully selected subset of patients with severe complications.

To be eligible, a child would need bone marrow or stem cells from a "matched" donor with a low risk of rejection. Even then, the procedure has significant risks and there's always the chance of rejection of the transplanted marrow.

But even without a cure, kids with sickle cell disease can lead relatively normal lives. Medicines are available to help manage the pain, and immunizations and daily doses of penicillin (an antibiotic) can help prevent infection.

Infection used to cause many deaths in infants and young children with sickle cell disease, but thanks to penicillin (or a similar antibiotic, amoxicilin) and appropriate immunizations, kids are much more likely to live longer, healthier lives. Although penicillin isn't a cure, it can help prevent life-threatening infections due to bacteria that cause serious infections in the blood, meningitis, and pneumonia.

Most kids will require two daily doses of penicillin, as prescribed by their doctors, until they're at least 5 years old (and often older). They also should be fully immunized with the regular childhood vaccinations, as well as the pneumococcal vaccine and influenza and meningococcal vaccines. Folic acid supplements can help them continue to produce new RBCs.

Sometimes, kids who develop serious complications (such as recurrent acute chest syndrome, especially severe anemia, or stroke) may receive regular transfusions of red blood cells to prevent or treat these complications.

In 1998 the U.S. Food and Drug Administration (FDA) approved the drug hydroxyurea for use in adults with sickle cell disease; while it still has not been officially approved for use in children, it is now commonly used by pediatric specialists in certain circumstances.

Hydroxyurea increases the amount of fetal hemoglobin in blood cells, which interferes with the sickling process and makes RBCs less sticky. This helps decrease the frequency and intensity of painful episodes and other complications such as acute chest syndrome. Hydroxyurea has been proved to decrease pain and other complications in kids and adults. Research is continuing to determine the drug's long-term effects and safety.

When to Call the Doctor

Seek emergency medical attention immediately if your child develops any of the following:

• fever of 101ºF (38ºC) or higher
• pain that isn't relieved by oral medication
• chest pain
• shortness of breath or trouble breathing
• extreme fatigue
• severe headaches or dizziness
• severe stomach pain or swelling
• jaundice or extreme paleness
• painful erection in males
• sudden change in vision
• seizures
• weakness or inability to move any part of the body
• slurring of speech
• loss of consciousness
• numbness or tingling

Caring for Your Child

Your child should receive regular care from your primary care doctor as well as a hematologist (a blood specialist) or a sickle cell specialty clinic. It's important to share your concerns and discuss any new symptoms or complications with your child's health care team.

Your child also should drink lots of fluids, get plenty of rest, and avoid extreme temperatures.

Most people with sickle cell disease now live into middle age and often well beyond. A critical time is the first few years of life, which is why early diagnosis and treatment are so important.

Reviewed by: Robin E. Miller, MD
Date reviewed: July 2009