From Genetics Home Reference

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.

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.

What genes are related to sickle cell disease?

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.

Read more about the HBB gene.

How do people inherit sickle cell disease?

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.

Where can I find information about diagnosis or management of sickle cell disease?

These resources address the diagnosis or management of sickle cell disease and may include treatment providers.

Gene Review: Sickle Cell DiseaseThis link leads to a site outside Genetics Home Reference.

Genetic Testing Registry: Hb SS diseaseThis link leads to a site outside Genetics Home Reference.

MedlinePlus Encyclopedia: Sickle Cell AnemiaThis link leads to a site outside Genetics Home Reference.

MedlinePlus Encyclopedia: Sickle Cell TestThis link leads to a site outside Genetics Home Reference.

You might also find information on the diagnosis or management of sickle cell disease in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about sickle cell disease?

You may find the following resources about sickle cell disease helpful. These materials are written for the general public.

MedlinePlus – Health information (4 links)

Genetic and Rare Diseases Information CenterThis link leads to a site outside Genetics Home Reference. – Information about genetic conditions and rare diseases

Additional NIH Resources – National Institutes of Health (4 links)

Educational resources – Information pages (18 links)

Patient support – For patients and families (8 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene ReviewsThis link leads to a site outside Genetics Home Reference. – Clinical summary

Genetic Testing Registry – Repository of genetic test information (1 link)

ACT Sheets – Newborn screening follow up (3 links)

ClinicalTrials.govThis link leads to a site outside Genetics Home Reference. – Linking patients to medical research

PubMedThis link leads to a site outside Genetics Home Reference. – Recent literature

OMIMThis link leads to a site outside Genetics Home Reference. – Genetic disorder catalog

What other names do people use for sickle cell disease?

HbS disease

Hemoglobin S Disease

SCD

Sickle cell disorders

Sickling disorder due to hemoglobin S

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about sickle cell disease?

Ask the Genetic and Rare Diseases Information CenterThis link leads to a site outside Genetics Home Reference..

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

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?

If a genetic disorder runs in my family, what are the chances that my children will have the condition?

Why are some genetic conditions more common in particular ethnic groups?

These links provide additional genetics resources that may be useful.

Genetics and health

Resources for Patients and Families

Resources for Health Professionals

What glossary definitions help with understanding sickle cell disease?

anemia ; atypical ; autosomal ; autosomal recessive ; cell ; complication ; FAE ; FAS ; gene ; heart failure ; hemoglobin ; hypertension ; jaundice ; molecule ; mutation ; newborn screening ; oxygen ; protein ; pulmonary ; recessive ; screening ; subunit ; thalassemia

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References (8 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional.

For more on this story go to:

http://ghr.nlm.nih.gov/condition/sickle-cell-disease

Also see iNews notice from GIS published today (12) at: http://www.ieyenews.com/2013/06/sickle-cell-support-group-meeting-3/