OTHER DISORDER

Disorder Name: Sickle Cell Disease
Acronym: SCD
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• What is Sickle cell disease (SCD)?
• What causes SCD?
• What are the symptoms of SCD?
• What is the treatment for SCD?
• What happens when SCD is treated?
• What causes the red blood cells to be sickle-shaped?
• How is SCD inherited?
• Is genetic testing available?
• What other testing is available?
• Can you test during a future pregnancy?
• Can other members of the family have SCD or be carriers?
• Can other family members be tested?
• How many people have SCD?
• Does SCD happen more often in a certain ethnic group?
• Does SCD go by any other names?
• Where can I find more information?

This fact sheet has general information about sickle cell disease (SCD). Every child is different and some of this information may not apply to your child specifically. Certain treatments may be recommended for some children but not others. If you have specific questions about SCD and available treatments, you should contact your doctor.

The management recommendations in this factsheet pertain to sickle cell disease caused by having hemoglobinHemoglobin is the protein in red blood cells that carries oxygen from the lungs throughout the body. In each red blood cell, there are hundreds of hemoglobin molecules. Hemoglobin molecules are made of two subunits, alpha and beta. Both the alpha and beta subunits are needed for hemoglobin to function correctly. When there is a change in the way hemoglobin is made, the red blood cells cannot deliver oxygen as efficiently. SS, which is the most common type of SCD. If your child has a different type of sickle cell disease such as hemoglobin SC or hemoglobin beta-thalassemia, ask your doctor for more specific information about that specific condition.

WHAT IS SICKLE CELL DISEASE (SCD)?

SCD is an inherited blood disorder that results in chronic health problems. People with SCD have abnormal hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen from the lungs to the rest of the body. Abnormal, or sickle-shaped, hemoglobin cannot deliver enough oxygen to the rest of the body. This causes individuals with SCD to experience episodes of pain. Over time, lack of oxygen damages the organs, especially the spleenThis is an organ located behind the stomach. It gets rid of old blood cells and helps fight infection. The spleen can enlarge in people with cirrhosis or with certain metabolic disorders., brain, lungs, and kidneys. SCD also causes anemiaThis is a condition in which the blood has too few red blood cells or too little hemoglobin, the oxygen carrying molecule in the blood. People with anemia are often pale, tired, weak, dizzy and short of breath., or a low number of red blood cellsRed blood cells are the major component in blood that delivers oxygen from the lungs to the body tissues..

There are several types of SCD, including hemoglobin SS, hemoglobin SC, and hemoglobin S-beta thalassemia. The most common type of SCD is hemoglobin SS. The different types of SCD have some symptoms in common and some symptoms that are unique to each different type of SCD. It is important to find out which type of SCD your child has and talk with your doctor about signs, symptoms, and treatment specific to that condition.

WHAT CAUSES SCD?

SCD is an inheritedAcquiring a trait from one’s parents. Most traits, such as eye color or hair color, are inherited from a parent through genes. condition that occurs when the body makes abnormally shaped hemoglobin. Normally, hemoglobin is shaped like a disk or doughnut so that it can move through the blood vessels easily. In people with SCD, hemoglobin is long and narrow, or “sickle-shaped.” Red blood cellsThe smallest living unit. Cells make up all organs and tissues in multi-cellular organisms, like humans. They can also live independently, as in bacteria and other microorganisms. At a minimum, a cell is surrounded by a membrane, contains DNA at some stage in its life, and is able to replicate itself into two equal parts. with sickled hemoglobin are stiff and fragile. They can get caught up with each other to form clumps within the blood vessels, so oxygen is not delivered effectively. Therefore, the body tissues and organs lack oxygen. When there is not enough oxygen in the body tissues, anemia, pain, and organ damage can occur.

Sickle cells also die more quickly than normal red blood cells. The bone marrow cannot make enough new cells to replenish the blood supply. Having too few red blood cells causes anemia.

SCD is not contagious. You cannot get SCD from living with, touching, or spending time with a person with SCD.

WHAT ARE THE SYMPTOMS OF SCD?

SCD causes minimal effects in some people and more serious problems in others. While SCD can cause many symptoms, most people with SCD do not develop all of the symptoms. Symptoms can be chronicAny condition that lasts for a long period of time or occurs frequently. For example, diabetes and hemochromatosis are both chronic conditions. (on-going or long-term) or acute (immediate or short-term). It is important to be educated about the symptoms so that they can be properly managed.

The symptoms of SCD are related to anemia, pain, or the effects of SCD on specific body parts.

Most infants do not show signs of SCD until they are a few months old. Often, the first sign of SCD is pain or swelling in the child’s hands or feet when small blood vessels become blocked. This causes some children to develop a fever.

Signs of anemia include:

• Fatigue (feeling tired or weak)
• Shortness of breath
• Dizziness
• Headaches
• Cold hands or feet
• Pale skin
• Chest pain

Pain episodes

Most people with SCD experience pain at some point in their life. An episode of pain that occurs because tissues do not have enough oxygen is called a sickle cell crisisA sickle cell crisis is an episode of pain that occurs in people with sickle cell disease when they do not have enough oxygen in their tissues.. Some people with SCD have one or fewer pain episodes each year, while others can have more than fifteen episodes. Sickle cell crises can affect any part of the body, but most often affect the bones, lungs, abdomen, and joints. Crises can be acute, lasting hours or days, or chronic, lasting weeks to months. They can be mild or severe. Many times, the exact cause of a sickle cell crisis is unknown, but it is likely that many factors contribute. Dehydration and infection are known to increase the chance of having a crisis. In children with SCD, sickle cell crises are the leading cause of hospitalizations and missed days of school.

Symptoms caused by blocked blood vessels

StrokeThis is when the blood or oxygen supply to part of the brain is stopped. It can be caused either by a blood clot or a leak in a blood vessel. A stroke may cause loss of speech and language and the ability to move certain body parts. If severe, it can cause death. and silent cerebral infarcts – A stroke or silent cerebral infarct can occur if sickle cells block blood vessels to the brain. Some strokes have physical signs such as paralysis on one side of the body or loss of speech, and others are only seen on MRIThis test uses magnetic waves to make pictures of the body. It can sometimes be used instead of x-rays to look at areas inside the body. It is often used to look at the brain or other inner organs.. Silent cerebral infarcts are only seen on MRI. Strokes and silent cerebral infarcts can cause permanent brain damage.

Spleen problems – The spleen is an organ that removes damaged red blood cells and fights infection. Sickle cells can clog the spleen. This not only weakens the spleen’s ability to fight infections but can cause pain on the left side of the abdomen.

Lung problems – Blocked blood vessels in the lungs cause symptoms such as wheezing, difficulty breathing, chest pain, and fever. This is called acute chest syndromeA group of symptoms and clinical findings that, when found together, make up a particular condition or disease.. Children with these symptoms often require hospitalization.

Vision problems – Blocked blood vessels in the eye can lead to blindness over time by damaging the retina.

Priapism – When blood vessels leading out of the penis are blocked, some boys with SCD experience painful erections.

Other symptoms

Increased risk for infection – Infants and young children with SCD are at an increased risk to develop infections, including those that are life-threatening. Taking penicillin daily and receiving immunizations can prevent infection.

Anemia – Individuals with SCD have anemia due to the sickled red blood cells dying faster than normal.

GallstonesGallstones are hardened balls of digestive fluid that form in the gallbladder. The gallbladder is the organ that releases digestive fluid during digestion. Gallstones can be as small as a grain of sand or as large as a golf ball. They cause no symptoms in some people and many complications in others. Signs of gallstones include yellowing of the eyes and pain in the upper right abdomen. – Small hardened deposits of bile form in the gallbladder causing yellow eyes and pain in right side of abdomen.

Slow growth – Children with SCD tend to grow more slowly and begin puberty later than their peers.

Ulcers – Wounds that don’t heal well may develop on your child’s lower leg.

SCD does not affect intelligence or the ability to learn. People with SCD are able to attend regular school when they are healthy. Many people with SCD reach their educational goals and have full-time jobs.

While there are many complications in SCD, the effects can be lessened when parents know what to do when complications arise.

WHAT IS THE TREATMENT FOR SCD?

Children with SCD are cared for by a team of specialists, including a hematologistA hematologist is a doctor who specializes in treating patients with blood disorders. Children with inherited blood conditions may have frequent check-ups with a hematologist., a doctor who specializes in treating blood disorders. The main goal of treatment is to prevent complications and lessen them when they do occur. Your child’s individual treatment plan may depend on the symptoms that s/he is experiencing. Parents’ awareness of signs of complications is crucial to providing rapid treatment.

Prevent infection
Infection is the leading cause of death in children with SCD. It is very important that children with SCD take penicillinPenicillin is a prescription medication that works to prevent infections. Children with sickle cell disease take penicillin daily. Talk with your doctor about the risks and benefits of taking penicillin. daily to prevent infection.

Have your child receive all of the usual childhood vaccinations according to the regular schedule. In addition, children with SCD should receive:

• Meningococcal vaccine to prevent meningitis (infection of the lining of the brain)
• Pneumococcal vaccine to protect against other serious bacterial infections
• Yearly flu shot

Teach your child good hand washing techniques.

Pain Management
Mild sickle cell crises can be treated with over-the-counter pain medications (such as acetaminophen and ibuprofen) or heating pads. More severe pain may be managed with prescription drugs or hospitalization.

Medications
Some adults with severe SCD take a drug called hydroxyurea to prevent crises. The long-term effects of using this drug during childhood are unknown. Glutamine is an FDA-approved drug for individuals over the age of 5 with SCD and may decrease the frequency of sickle cell pain-related episodes.  Other medications (Crizanlizumab, Voxelotor and others) may be used depending on your child’s age and the complications they may be experiencing.

Blood transfusion
A blood transfusion may be used to treat a sickle cell crisis or prevent a stroke. Some children with SCD receive blood transfusions on a regular basis. However, frequent blood transfusions can cause the body to have a dangerously high level of ironIron is a natural element that is needed for the body to function properly. Iron can be found in many foods. Having a high amount of iron can cause damage to organs. Talk with your doctor about the risks and benefits if your child takes iron supplements or has blood transfusions.. Talk with your doctor about the risks and benefits of blood transfusions.

Testing
Frequent testing of blood and urine samples can determine how a person’s red blood cells are working and check for infection and organ damage.

Some doctors recommend brain imaging studies to check for blood clots in the brain and X-rays to check for lung infection and bone damage.

Eye Check-ups
Routine eye check-ups are important to prevent vision problems or blindness from damaged blood vessels in the eye. Children who have difficulty seeing may have trouble in school.

Activities
Children with SCD should avoid activities which expose them to extreme temperatures (swimming in cold water) or high altitudes (backpacking, hiking, and skiing). If participating in these activities, children should plan for temperature differences (i.e., use of gloves, warm clothes) and approach activities with caution and prevention of symptoms in mind. Children with SCD can participate in other normal activities, but should make sure to stay hydrated and rest when tired.

Nutrition
To prevent pain crises, children with SCD need to drink plenty of water, especially when the child is sick, active, or in hot weather. Most children with SCD have bedwetting episodes, for which there are strategies such as limiting drinks before bedtime and waking the child during sleep to urinate.

Children older than one year of age may take folic acid daily to stimulate red blood cell production.

Since some children with SCD, especially those receiving blood transfusions, accumulate iron in their blood, they should not be given iron supplements.

Call your doctor at the start of any illness
Sometimes, minor illnesses can be signs of more severe complications of SCD. In order to prevent problems, call your doctor right away if your child has any of the following:

• Fever of 101 degrees or higher
• Signs of infection (chills, lethargyAbnormal drowsiness., irritability, poor feeding, vomiting)
• Severe headache or dizziness
• Chest pain or trouble breathing
• Severe stomach pain or swelling
• Sudden pale coloring or jaundiceThis is a yellow color to the skin and whites of the eyes. It is often a sign of liver damage.
• Painful erection
• Sudden change in behavior – seizuresThese are also called "convulsions" or "fits." During a seizure, a person loses consciousness and control of his or her muscles. It may also cause involuntary movements. Seizures can happen for many reasons. Some causes are metabolic disorders, a metabolic crisis, brain injury, and infection., paralysis, can’t wake up
• Painful swelling of hands and feet

Parents’ awareness of warning signs of complications is crucial to treatment.

Bone MarrowBone marrow is the tissue that is located around the hollow center of bones. Bone marrow produces new red blood cells. (Stem Cell) Transplant
Bone marrow transplantation is a potential cure for SCD. Stem cells are a type of cell found in bone marrow. Bone marrow produces red blood cells. A person with sickle cell disease has bone marrow that produces red blood cells sickled hemoglobin. By replacing that bone marrow with healthy bone marrow, a person’s body may start to produce normal hemoglobin. In order to have a bone marrow transplantWhen a person does not have enough working red blood cells, they may have a bone marrow transplant. In this surgical procedure, bone marrow is removed from another person (donor) and implanted into the patient. The patient and bone marrow donor must be a genetic match. There are many risks associated with bone marrow transplants., a geneticRelating to (or due to) genes and heredity or the field of studying genes and heredity. match must be found. There are risks associated with the transplant and this option should be discussed with your medical team.

Gene TherapyGene therapy – a type of treatment that transplants normal working genes into cells to replace non-working genes in order to treat genetic disorders. There are many ways that gene therapy can be done. Sometimes, a gene with a disease-causing variant can be replaced with a healthy gene. Sometimes, a gene with a disease-causing mutation can be inactivated or “silenced.” And sometimes, a new gene can be put into the body to help fight a disease. Some gene therapies are still experimental.
You may read information about the potential for gene therapy to treat or cure SCD.  Researchers are currently working on different types of gene therapies for SCD. Gene therapy is only available as part of a research study and is not FDA-approved yet. Currently, the only way to receive treatment with gene therapy is to participate in a clinical trialClinical trials test the effectiveness of new drugs or treatments. These studies determine how well the treatments work, what risks are associated with them, and whether they work better than the current treatment..  People with SCD must meet strict eligibility criteria and be informed about the potential risks and benefits of being part of a clinical trial. Your medical team can talk to you more about gene therapy.

WHAT HAPPENS WHEN SCD IS TREATED?

The goal of treatment is to lessen the health problems that occur with SCD. However, even when a child receives proper medical care and prevention, symptoms can still occur.

You may be advised to see a hematologist, a doctor who specializes in caring for children with blood disorders. These doctors can work with your regular pediatrician to ensure up-to-date treatment for your child. Some centers have multidisciplinary sickle cell clinics that provide all of the child’s needs in one place.

WHAT CAUSES THE RED BLOOD CELLS TO BE SICKLE-SHAPED?

Genes tell the body how to make proteins. SCD is caused by changes called variantsA variant is a change or alteration in a person’s DNA sequence. Variants can happen in genes and affect how the gene functions. There are different types of variants – they can be non-problem causing (benign), disease-causing (pathogenic) or of unknown significance. The term variants is now used in place of the term mutation. in the HBB gene. An error in the DNADeoxyribonucleic acid (DNA) is a molecule found in the chromosomes that carries genetic information. DNA is composed of four units (called bases) that are designated A, T, G, and C. The sequence of the bases spell out instructions for making all of the proteins needed by an organism. A gene is a section of DNA that holds the instructions for a specific protein. A change in one or more of the DNA bases making up a gene is called a mutation. Some mutations change the protein instructions and can lead to particular health problems or disorders. Each parent passes half of their chromosomes, and thus half of their DNA instructions, onto their children. It is these instructions that cause certain traits, such as eye or hair color, to be inherited. spelling of the gene for hemoglobin, called a variant, causes the hemoglobin proteinA molecule that makes up many parts of every cell in the body. Examples of proteins include hormones, enzymes, hair, and antibodies. Proteins are made up of 20 different types of individual units called amino acids. It is the order of these amino acids in a protein that determines what form and function a protein has. Each gene holds the instructions for making a single protein. to be shaped abnormally. People with SCD have a variant in both copies of the HBB gene. Everyone with SCD has the same variant that causes hemoglobin to be sickle-shaped.

Different variants in the HBB gene cause the different types of SCD. People with hemoglobin SS have the sickle cell gene variant in both copies. People with hemoglobin SC have a gene variant that makes another type of abnormal hemoglobin (type C). People with hemoglobin S-beta thalassemia have a different gene variant that causes abnormal hemoglobin.

HOW IS SCD INHERITED?

SCD is inherited in an autosomal recessive manner, meaning that a child must have changes in both copies of their HBB gene to have SCD. Since each parent gave their child one copy of the HBB gene, we know that both parents of a child with SCD have a change in one of their hemoglobin genesA segment of DNA that contains the instructions to make a specific protein (or part of a protein). Genes are contained on chromosomes. Chromosomes, and the genes on those chromosomes, are passed on from parent to child. Errors in the DNA that make up a gene are called variants and can lead to diseases..

Parents of children with SCD do not necessarily have SCD. A parent can have a single gene for abnormal hemoglobin, but the other HBB gene is working correctly. In this case, a parent is called a carrier or said to have sickle cell traitPeople with sickle cell trait have one working copy of the sickle cell gene and one non-working copy. Having sickle cell trait does not cause a person to be sick. A person with sickle cell trait can pass it on to his/her children and may be at risk to have a child with sickle cell disease. About 1/12 African Americans has sickle cell trait. Talk with your doctor about testing for sickle cell trait.. CarriersA person who has one copy of a gene mutation for a particular autosomal recessive disorder (remember genes come in pairs). Carriers are not affected by the disorder. However, they can pass on the gene variant to their children. Children who inherit two such gene variants will be affected by the disorder. The term variants is now used in place of the term mutation. do not have SCD because the other HBB gene is working correctly.

When both parents are carriers, there is a 25% chance in each pregnancy for the child to have SCD. There is a 50% chance for the child to be a carrier, just like the parents. Finally, there is a 25% chance for the child to have two working genes.

Parents may have different variants in the hemoglobin genes that could cause the different types of SCD.

Genetic counseling is available to families who have children with SCD. Genetic counselors can answer your questions about how SCD is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a genetic counselorThese are health care providers who have special training in genetic conditions. They help families understand genetic disorders and how they are passed down. Genetic counselors offer information and support to people who have genetic conditions in their families or are concerned that they may have a child with an inherited disorder..

IS GENETIC TESTING AVAILABLE?

Genetic testing for SCD can be done on a blood sample. Genetic testing, also called DNA testing, looks for genetic variants in HBB genes that cause SCD. If you have questions about genetic testing, talk with your genetic counselor or hematologist. For most children, genetic testing is not necessary for diagnosis. However, it can be helpful for carrier testing or prenatal diagnosis, discussed below.

WHAT OTHER TESTING IS AVAILABLE?

Newborn ScreeningA screening test that looks for different disorders using a small sample of blood taken from a newborn’s heel. A positive or abnormal newborn screening result means that there are slight differences that were found in the baby’s blood, and further testing is needed to figure out if the baby has a metabolic disorder.
Newborn screening for SCD is now done in all states. A blood spot from a prick on a baby’s heel is used to screen for a number of different genetic conditions. The initial newborn screeningThe process of testing for disease in a person who does not show signs of having the disease (nonsymptomatic or asymptomatic person). The goal of screening is to catch the disease in its early stages. test determines the amount of normal hemoglobin in the blood spot. If too little normal hemoglobin is found on the initial newborn screening, another test is performed. If the second test is also abnormal, the parents are notified and the child is referred to a specialist for an evaluation.

Confirmatory Testing
When your child is around six weeks old, s/he will need to have a confirmatory test performed on a second blood sample. If test results are still unclear, genetic testing may need to be performed on another blood sample.

It is important to complete blood tests at the different points in time recommended by your doctor because the body produces different types of hemoglobin in infancy and adulthood. In the first few months of life, all babies still have some fetal hemoglobin. Therefore, the levels of the different types of hemoglobin need to be compared at different time points in order to establish a definitive diagnosis.

CAN YOU TEST DURING A FUTURE PREGNANCY?

If both gene changes have been found in your child with SCD, DNA testing can be done in future pregnancies. The sample needed for this test is obtained by either CVS or amniocentesisThis is a test done during pregnancy. A needle is used to remove a small sample of fluid from the sac around the fetus. The sample can be used to test for certain genetic disorders in the fetus. Amniocentesis to test for genetic conditions is usually done between 13 and 20 weeks of pregnancy.. Parents may either choose to have testing during pregnancy or wait until birth to have the baby tested. Parents may also choose to use assisted reproductive techniques to decrease the chance that their future children would have SCD. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.

CAN OTHER MEMBERS OF THE FAMILY HAVE SCD OR BE CARRIERS?

Having SCD
The brothers and sisters of a baby with SCD also have a chance of being affected, even if a parent has not noticed any symptoms. Finding out whether other children in the family have SCD is important because early treatment may prevent health problems. Talk to your doctor or genetic counselor about testing your other children for SCD.

SCD Carriers
SCD carriers are not anemic and will generally not have symptoms of SCD. This is because carriers have a working HBB gene to make up for the abnormal one.

Brothers and sisters who do not have SCD still have a chance to be carriers. Except in special cases, carrier testing should only be done on people over 18 years of age.

If you are a parent of a child with SCD, your brothers and sisters have a 50% chance to also be a SCD carrier. It is important to talk to other family members about their risk of being carriers. There is a small chance they are also at risk to have children with SCD.

When both parents are known to be carriers, newborn screening results are not sufficient to rule out SCD in a newborn baby. In this case, further testing should be done in addition to newborn screening.

CAN OTHER FAMILY MEMBERS BE TESTED?

Diagnostic testing
If both genetic variants have been found in your child with SCD, brothers and sisters can be tested for SCD using DNA testing on a blood sample or a cheek swabThis is a cotton covered stick that is used to painlessly collect cells from the inside of the mouth. The cotton tip is swirled on the inside of the cheek and then placed in a sterile tube. The cells collected are used for specific genetic tests.. Other special tests may also be suggested.

Carrier Testing
If both gene changes have been found in your child with SCD, other family members can have DNA testing on a blood sample or cheek swab to see if they are carriers.

HOW MANY PEOPLE HAVE SCD?

Each year, around 2,000 babies are born with SCD in the United States. About one in every 250-600 African- American babies in the United States is born with SCD. SCD is less common in children of other ethnic backgrounds.

DOES SCD HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?

SCD occurs most often in people with African ancestry. About 1 in every 12 African Americans is a carrier for SCD. People of Mediterranean, Middle Eastern, Indian, Caribbean, South American, and Central American descent are also at an increased risk of being a carrier. However, SCD can affect people of any ethnic background.

DOES SCD GO BY ANY OTHER NAMES?

Hemoglobin SS, the most common type of SCD, may also be called:

• Sickle cell anemia
• Hemoglobin S Disease

WHERE CAN I FIND MORE INFORMATION?

Sickle Cell Disease Association of America
http://www.sicklecelldisease.org

Sickle Cell Information Center
http://www.scinfo.org

MedlinePlus
https://medlineplus.gov/genetics/condition/sickle-cell-disease/

DOCUMENT INFO:

Created by:	www.newbornscreening.info
Reviewed by:	HI, CA, OR, and WA metabolic specialists
Review date:	November 30, 2012 June 3, 2020 March 15, 2023
Update on:	March 15, 2023

 

DISCLAIMER:

THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content (“Content”), including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET. This project is supported by a grant from the MaternalHaving to do with the mother. and Child Health Bureau, Health Resources and Service Administration, Genetic Services Branch, MCH Project #:UH7MC30774-01-00 http://mchb.hrsa.gov