cia confidentiality integrity availability

Skip to main content

U.S. National Library of Medicine

  • Email This Page
  • Share on Facebook
  • Share on Twitter

Genetics Home Reference, Your Guide to Understanding Genetic Conditions

  1. Home
  2. Health Conditions
  3. Sickle cell disease

Sickle cell disease

Printable PDF Open All Close All

Description

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.

Signs and symptoms of sickle cell disease usually begin in early childhood. 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. 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. 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.

Normal blood cells (left) and blood cells in Sickle cell disease, which do not flow through the circulatory system smoothly.

    • Enlarge

    Frequency

    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.

    Related Information

    • What information about a genetic condition can statistics provide?
    • Why are some genetic conditions more common in particular ethnic groups?

    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.

    Learn more about the gene associated with sickle cell disease

    • HBB

    Related Information

    • What is a gene?
    • What is a gene mutation and how do mutations occur?
    • How can gene mutations affect health and development?
    • More about Mutations and Health

    Inheritance Pattern

    This condition is inherited in an autosomal recessive pattern , which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

    Related Information

    • What does it mean if a disorder seems to run in my family?
    • What are the different ways in which a genetic condition can be inherited?
    • More about Inheriting Genetic Conditions

    Diagnosis & Management Links

    Formal Diagnostic Criteria (3 links)

    • ACT Sheet: FS (PDF)
    • ACT Sheet: FSA (PDF)
    • ACT Sheet: FSC (PDF)

    Genetic Testing Information (2 links)

    • What is genetic testing?
    • Genetic Testing Registry: Hb SS disease

    Research Studies from ClinicalTrials.gov (1 link)

    • ClinicalTrials.gov

    Other Diagnosis and Management Resources (8 links)

    • Baby’s First Test: S, Beta-Thalassemia
    • Baby’s First Test: S, C Disease
    • Baby’s First Test: Sickle Cell Anemia
    • GeneReview: Sickle Cell Disease
    • Genomics Education Programme (UK)
    • Howard University Hospital Center for Sickle Cell Disease
    • MedlinePlus Encyclopedia: Sickle Cell Anemia
    • MedlinePlus Encyclopedia: Sickle Cell Test

    Related Information

    • How we cover diagnosis and management of health conditions
    • How are genetic conditions diagnosed?
    • How are genetic conditions treated or managed?
    • How can I find a genetics professional in my area?

    Other Names for This Condition

    • HbS disease
    • Hemoglobin S Disease
    • SCD
    • Sickle cell disorders
    • Sickling disorder due to hemoglobin S

    Related Information

    • How are genetic conditions and genes named?

    Additional Information & Resources

    Health Information from MedlinePlus (4 links)

    • Encyclopedia: Sickle Cell Anemia
    • Encyclopedia: Sickle Cell Test
    • Health Topic: Newborn Screening
    • Health Topic: Sickle Cell Disease

    Genetic and Rare Diseases Information Center (1 link)

    • Sickle cell anemia

    Additional NIH Resources (4 links)

    • GeneEd
    • National Heart, Lung, and Blood Institute
    • National Human Genome Research Institute
    • National Library of Medicine: Changing the Face of Medicine

    Educational Resources (18 links)

    • About Sickle Cell Disease
    • Action Medical Research for Children (UK)
    • American Sickle Cell Anemia Association: Changing Faces, Changing Shapes (video)
    • DNA Learning Center from Cold Spring Harbor Laboratory: Sickle Cell Anemia, 3D Animation with Narration
    • Genetic Science Learning Center, University of Utah
    • Illinois Department of Public Health
    • Information Center for Sickle Cell and Thalassemic Disorders
    • MalaCards: sickle cell disease
    • Merck Manual of Medical Information, Second Home Edition
    • Michigan Department of Community Health (PDF)
    • Nemours Foundation
    • Orphanet: Sickle cell anemia
    • Swedish National Board of Health and Welfare
    • University of Rochester Medical Center
    • Virginia Department of Health (PDF)
    • Washington State Department of Health: Hemoglobin S Fact Sheet (PDF)
    • Your Genes Your Health from Cold Spring Harbor Laboratory
    • Your Genome from Wellcome Genome Campus

    Patient Support and Advocacy Resources (5 links)

    • American Sickle Cell Anemia Association
    • March of Dimes
    • National Organization for Rare Disorders (NORD)
    • Sickle Cell Disease Association of America
    • The Sickle Cell Information Center

    Clinical Information from GeneReviews (1 link)

    • Sickle Cell Disease

    Scientific Articles on PubMed (1 link)

    • PubMed

    Catalog of Genes and Diseases from OMIM (1 link)

    • SICKLE CELL ANEMIA

    Sources for This Page

    • Ashley-Koch A, Yang Q, Olney RS. Sickle hemoglobin (HbS) allele and sickle cell disease: a HuGE review. Am J Epidemiol. 2000 May 1;151(9):839-45. Review.
      Citation on PubMed
    • Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004 Feb 26;350(9):886-95.
      Citation on PubMed
    • Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C. Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore). 2005 Nov;84(6):363-76.
      Citation on PubMed
    • Schnog JB, Duits AJ, Muskiet FA, ten Cate H, Rojer RA, Brandjes DP. Sickle cell disease; a general overview. Neth J Med. 2004 Nov;62(10):364-74. Review.
      Citation on PubMed
    • Serjeant GR. The emerging understanding of sickle cell disease. Br J Haematol. 2001 Jan;112(1):3-18. Review.
      Citation on PubMed
    • Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004 Oct 9-15;364(9442):1343-60. Review.
      Citation on PubMed
    • Vichinsky E. New therapies in sickle cell disease. Lancet. 2002 Aug 24;360(9333):629-31. Review.
      Citation on PubMed
    • Vichinsky EP. Pulmonary hypertension in sickle cell disease. N Engl J Med. 2004 Feb 26;350(9):857-9.
      Citation on PubMed

    More from Genetics Home Reference

    Recently Added Pages

    • Asparagine synthetase deficiency
    • Carpal tunnel syndrome
    • Congenital anomalies of kidney and urinary tract
    • All Recently Added Pages

    Noteworthy

    • Celebrating National Family Health History Day
    • Crick, Watson, and Wilkins Awarded Nobel Prize 56 Years Ago

    You Might Also Like

    • What is direct-to-consumer genetic testing?
    • What are genome editing and CRISPR-Cas9?
    • What is precision medicine?
    • What is newborn screening?

    Reviewed : August 2012

    Published : December 4, 2018

    The resources on this site should not be used as a substitute for professional medical care or advice. Users with questions about a personal health condition should consult with a qualified healthcare professional .

    How Is Sickle Cell Anemia Inherited?

    Medically reviewed by Karen Gill, MD on October 1, 2018 — Written by Jill Seladi-Schulman, PhD

    What is sickle cell anemia?

    Sickle cell anemia is a genetic condition that’s present from birth. Many genetic conditions are caused by altered or mutated genes from your mother, father, or both parents.

    People with sickle cell anemia have red blood cells that are shaped like a crescent or sickle. This unusual shape is due to a mutation in the hemoglobin gene. Hemoglobin is the molecule on red blood cells that allows them to deliver oxygen to tissues throughout your body.

    The sickle-shaped red blood cells can lead to a variety of complications. Due to their irregular shape, they can become stuck within blood vessels, leading to painful symptoms. Additionally, sickle cells die off faster than typical red blood cells, which can lead to anemia .

    Some, but not all, genetic conditions can be inherited from one or both parents. Sickle cell anemia is one of these conditions. Its inheritance pattern is autosomal recessive. What do these terms mean? How exactly is sickle cell anemia passed on from parent to child? Read on to learn more.

    What’s the difference between a dominant and recessive gene?

    Geneticists use the terms dominant and recessive to describe the likelihood of a particular trait being passed on to the next generation.

    You have two copies of each of your genes — one from your mother and another from your father. Each copy of a gene is called an allele. You may receive a dominant allele from each parent, a recessive allele from each parent, or one of each.

    Dominant alleles usually override recessive alleles, hence their name. For example, if you inherit a recessive allele from your father and a dominant one from your mother, you’ll usually display the trait associated with the dominant allele.

    The sickle cell anemia trait is found on a recessive allele of the hemoglobin gene. This means that you must have two copies of the recessive allele — one from your mother and one from your father — to have the condition.

    People who have one dominant and one recessive copy of the allele won’t have sickle cell anemia.

    Is sickle cell anemia autosomal or sex-linked?

    Autosomal and sex-linked refer to the chromosome that the allele is present on.

    Each cell of your body typically contains 23 pairs of chromosomes. Out of each pair, one chromosome is inherited from your mother and the other from your father.

    The first 22 pairs of chromosomes are referred to as autosomes and are the same between males and females.

    The last pair of chromosomes are called sex chromosomes. These chromosomes differ between the sexes. If you’re female, you’ve received an X chromosome from your mother and an X chromosome from your father. If you’re male, you’ve received an X chromosome from your mother and a Y chromosome from your father.

    Some genetic conditions are sex-linked, meaning that the allele is present on the X or Y sex chromosome. Others are autosomal, meaning that the allele is present on one of the autosomes.

    The sickle cell anemia allele is autosomal, meaning it can be found on one of the other 22 pairs of chromosomes, but not on the X or Y chromosome.

    How can I tell if I’ll pass on the gene to my child?

    In order to have sickle cell anemia, you must have two copies of the recessive sickle cell allele. But what about those with only one copy? These people are known as carriers. They’re said to have sickle cell trait , but not sickle cell anemia.

    Carriers have one dominant allele and once recessive allele. Remember, the dominant allele usually overrides the recessive one, so carriers generally don’t have any symptoms of the condition. But they can still pass the recessive allele on to their children.

    Here are a few example scenarios to illustrate how this might happen:

    • Scenario 1. Neither parent has the recessive sickle cell allele. None of their children will have sickle cell anemia or be carriers of the recessive allele.
    • Scenario 2. One parent is a carrier while the other isn’t. None of their children will have sickle cell anemia. But there’s a 50 percent chance that children will be carriers.
    • Scenario 3. Both parents are carriers. There’s a 25 percent chance that their children will receive two recessive alleles, causing sickle cell anemia. There’s also a 50 percent chance that they will be a carrier. Lastly, there’s also a 25 percent chance that their children won’t carry the allele at all.
    • Scenario 4. One parent isn’t a carrier, but the other has sickle cell anemia. None of their children will have sickle cell anemia, but they’ll all be carriers.
    • Scenario 5. One parent is a carrier and the other has sickle cell anemia. There’s a 50 percent chance that children will have sickle cell anemia and a 50 percent chance they’ll be carriers.
    • Scenario 6. Both parents have sickle cell anemia. All of their children will have sickle cell anemia.

    How do I know if I’m a carrier?

    If you have a family history of sickle cell anemia, but you don’t have it yourself, you may be a carrier. If you know others in your family have it, or you’re not sure about your family history, a simple test can help to determine whether you carry the sickle cell allele.

    A doctor will take a small blood sample, usually from a fingertip, and send it off to a laboratory for analysis. Once the results are ready, a genetic counselor will go over them with you to help you understand your risk of passing the allele on to your children.

    If you do carry the recessive allele, it’s a good idea to have your partner take the test as well. Using the results of both of your tests, a genetic counselor can help you both understand how sickle cell anemia may or may not affect any future children you have together.

    The bottom line

    Sickle cell anemia is a genetic condition that has an autosomal recessive inheritance pattern. This means that the condition isn’t linked to the sex chromosomes. Someone must receive two copies of a recessive allele in order to have the condition. People that have one dominant and one recessive allele are referred to as carriers.

    There are many different inheritance scenarios for sickle cell anemia, depending on the genetics of both of the parents. If you’re concerned that you or your partner could pass the allele or condition on to your children, a simple genetic test can help you navigate all the potential scenarios.