Beta thalassemia
Related Terms
Acute chest crisis, Anemia, aplastic crisis, autosomal recessive, beta thalassemia, genetic counseling, genetic testing, genetic screening, HBB gene, HbC, HbE, HbS disease, HbSBetaThal disease, HbSC disease, HbSE disease, hemoglobin C, hemoglobin E, hemoglobin S disease, mutation, newborn screening, pulmonary hypertension, recessive, SS disease, SCA, SCD, sickle cell anemia, sickle cell disease, sickling disorder due to hemoglobin S, sickle-hemoglobin C disease, sickle-hemoglobin E disease, sickle beta-plus-thalassemia, sickle beta-zero-thalassaemia, thalassaemia, thalassemia, vaso-occlusive crisis.
Background
Sickle cell disease (SCD) is a common name for several inherited disorders that affect red blood cells. SCD affects about 80,000 people in the United States, making it the most common blood disorder in the country. SCD occurs more frequently in certain populations, such as African Americans. In this population, about one out of every 400 people has the disorder.
SCD occurs in individuals who have defective forms of hemoglobin, the protein in red blood cells that carries oxygen. The defective hemoglobin causes red blood cells to assume an abnormal sickle (or C-like) shape. These irregular-shaped blood cells die early, causing a shortage of red blood cells.
Because anemia causes decreased oxygen in the blood, symptoms may include shortness of breath and fatigue. Anemia may also increase the risk of infections and may delay growth in children.
Sickle cell anemia (SCA), or SS disease, is the most common form of SCD. The terms "sickle cell anemia" and "sickle cell disease" are often used interchangeably.
The defective hemoglobin in SCA is caused by a mutation in a gene that contains the instructions for making hemoglobin. Individuals who inherit two copies of this mutation (one from each parent) will develop SCD. Individuals who inherit only one copy of the mutation may not have symptoms of SCD, but are known as "carriers" because they can pass on the mutation when they have children.
People with SCD are less likely to become infected with malaria, a common infectious disease caused by parasites of the genus Plasmodium (P. falciparum, P. vivax, P. ovale, and P. malariae). This is because the "sickled" red blood cells are somewhat resistant to infection by the malaria parasite. SCD carriers retain some of this resistance to malaria because some of their red blood cells are abnormal. Therefore, SCD occurs more frequently in areas where malaria is also common, including sub-Saharan Africa and other tropical or sub-tropical regions.
Because SCD may decrease oxygen levels in the blood, organs and tissues may be deprived of oxygen and serious damage may result.
Although SCD is a serious condition and generally considered to be incurable, a variety of treatments are available. With proper care, individuals with SCD can maintain relatively healthy lives. Many SCD patients may have normal or near-normal life expectancies.
Signs and symptoms
The signs and symptoms of sickle cell disease (SCD) are caused by abnormally shaped (sickled) red blood cells. These sickled red blood cells may break down or die prematurely, resulting in a shortage of red blood cells (anemia).
The symptoms of SCD often begin during early childhood. The severity of the symptoms may vary, ranging from mild to serious.
Because anemia causes decreased oxygen in the blood, symptoms may include fatigue and shortness of breath. Anemia may also increase the risk of infections and may delay growth in children.
Individuals with SCD may experience painful episodes when the abnormally shaped red blood cells become occluded (stuck) in small blood vessels. This may result in decreased oxygen in the blood, and serious damage can result when organs and tissues are deprived of oxygen.
SCD may also cause jaundice, indicated by a yellowing of the eyes and skin. In SCD, jaundice is caused by the rapid breakdown of red blood cells.
Diagnosis
High-performance liquid chromatography (HPLC): Tests for sickle cell disease (SCD) are performed routinely on newborns in most states. The most reliable SCD test involves a method called high-performance liquid chromatography (HPLC), which separates different forms of proteins in a column and can detect mutant forms of hemoglobin.
Blood sample: Blood samples may also be examined under a microscope for the characteristic sickle-shaped red blood cells. Abnormal red blood cells may be induced to sickle by adding the chemical sodium metabisulphite.
Sickle solubility test: A sickle solubility test may also be performed to diagnose SCD. In this procedure, hemoglobin is added to a sodium dithionite solution. The solution remains clear when normal hemoglobin is added. Abnormal hemoglobin causes the solution to become cloudy.
Hemoglobin may be isolated from blood and separated using gel electrophoresis. During this procedure, different proteins will migrate at different speeds through a gel when an electric current is applied. This allows different forms of hemoglobin to be identified.
Genetic (DNA) testing: DNA tests may also be performed to confirm the presence of a mutated HBB gene and confirm the results from other test methods. However, genetic tests are rarely used to diagnose SCD because other methods are accurate and widely available.
Amniotic fluid (prenatal) genetic testing: SCD may be diagnosed in a developing fetus using blood samples. Diagnosis of SCD may also be performed on a developing fetus through amniocentesis, during which the amniotic fluid surrounding the fetus is sampled through a needle. Blood cells from the amniotic fluid may indicate SCD. Genetic tests may also be performed on blood or amniotic fluid. Because taking a blood sample may cause harm to a fetus, taking samples of amniotic fluid is generally preferred. It is important to note that any prenatal test carries a risk of miscarriage.
Chorionic villus sampling (CVS): Chorionic villus sampling (CVS) is another type of prenatal diagnostic test that can detect genetic problems in a fetus. Samples are taken from the chorionic villus or placental tissue. As with any prenatal test, this procedure carries a risk of miscarriage.
Pre-implantation genetic diagnosis (PGD): A new procedure called pre-implantation genetic diagnosis (PGD) may be performed on embryos produced by in vitro (artificial) fertilization. This test allows parents to implant and carry only the embryos that do not carry the mutated genes that cause SCD.
Complications
General: Because sickle cell disease (SCD) may decrease oxygen levels in the blood, organs and tissues may be deprived from oxygen and serious damage can result.
Vaso-occlusive crisis: If the abnormally shaped red blood cells cause blockages (called occlusions) in the small blood vessels (capillaries), vaso-occlusive crisis can occur. This can restrict blood flow to an organ, resulting in lack of blood (ischemia), organ damage, and pain. Vaso-occlusive crisis is also known as pain crisis.
Vaso-occlusive crisis often restricts blood to the bones and bone ischemia can result in serious bone weakness.
High blood pressure around the lungs, or pulmonary hypertension, is a serious complication of SCD. Pulmonary hypertension affects about 1/3 of adults with SCD and can result in heart failure.
Blocking of the blood vessels may affect the spleen, which is an important organ of the immune system. Damage to the spleen may require removal of the organ or autosplenectomy.
Asplenia, or lack of the spleen, may significantly increase the risk for infections, particularly with bacterial influenza, pneumonia, or meningitis.
Acute chest crisis: A life-threatening complication of SCD is acute chest crisis or acute chest syndrome. The hallmarks of acute chest crisis include chest pain, shortness of breath, fever, hypoxemia (low oxygen in the blood), and abnormal chest X-rays. A particularly severe complication of acute chest crisis is atelectasis or collapsing of the lung. Vaso-occlusive (pain) crisis or respiratory infection may lead to acute chest syndrome.
Aplastic crisis: In patients with SCD, the bone marrow may temporarily stop producing red blood cells. This aplastic crisis usually occurs as a result of human parvovirus B19 infection. This infection often clears on its own and red blood cell production resumes. However, sometimes the number of red blood cells (hematocrit) falls so low that a blood transfusion is required. There is a high risk of other (secondary) infections during aplastic crisis, so individuals with aplastic crisis should be isolated to avoid secondary infections and the spreading of human parvovirus B19 infection.
Other complications: The rapid breakdown of red blood cells in SCD may lead to complications such as jaundice (yellowing of the eyes and skin) and gallstones.
The sickled red blood cells may block the flow of blood, which may lead to priapism (prolonged erection) and stroke. Improper blood flow may affect the retina, which is found in the back of the eye, and cause retinal disease (retinopathy), retinal detachment, or vision problems.
Organ damage may also result from the lack of blood flow/oxygen to the organ. Damage to the spleen may weaken the immune system and increase the risks of bacterial infections, such as osteomyelitis (bacterial bone infection) and hand-foot syndrome.
Women with SCD who become pregnant have an increased risk for pre-eclampsia (also called gestational hypertension), which is a disease of pregnancy that is marked by high blood pressure. Expectant mothers with SCD have higher rates of spontaneous abortion (miscarriage) and growth of the fetus may be impaired.
Impaired blood flow in the legs may cause leg ulcers to form.
A complication of pain treatments, particularly opioid (narcotic) therapy, is tolerance or addiction to pain medications.
Treatment
General: There is no cure for sickle cell disease (SCD), but treatment may help relieve symptoms. Treatment may include the administration of oxygen, pain-relieving drugs, and oral and intravenous fluids to reduce pain and prevent complications.
Routine eye examinations are advised, as vision problems may result when the vessels in the back of the eye become blocked. Laser surgery may be used to correct eye problems and prevent vision loss.
Blood transfusions: Blood transfusions may greatly reduce the risk of stroke in children with SCD. However, regular transfusions carry major risks, including blood infections and iron buildup in the body. Treatment with blood transfusions is not routine and should only be used after careful consultation with physicians who specialize in blood disorders.
Hydroxyurea (Croxia? or Hydrea?): A cancer drug called hydroxyurea (Droxia? or Hydrea?) is also used to treat sickle cell anemia in adults.
Pain relievers: Pain crises are treated according to symptoms with common pain relievers (called analgesics). These may include acetaminophen (Tylenol?), ibuprofen (Advil? or Motrin?), and aspirin.
Severe pain may require treatment with opioid (narcotic) drugs. Side effects of opiate use include itching, excessive thirst, nausea, fatigue, and opiate withdrawal. Diphenhydramine (Benadryl?) may relieve the itching associated with opioid use.
The most severe pain crises may require hospital stays and in-patient opioid treatment.
Antimicrobials: Infections associated with SCD may be treated with antibiotics. The types of antibiotics given will depend on the infection.
Vaccinations: Patients with SCD, particularly young children and infants, should receive routine vaccinations as well as additional vaccinations. These may include an annual influenza (flu) vaccine beginning at six months of age, a pneumococcal vaccine at ages two and five, and the meningococcal vaccine (which protects against meningitis) at age five.
Bone marrow transplant: In rare instances, a bone marrow transplant may be performed. Bone marrow transplantation is a high-risk procedure that requires bone marrow from a matching donor. This procedure is still considered experimental for treating SCD.
Integrative therapies
Strong scientific evidence:
Zinc: Zinc formulations have been used since ancient Egyptian times to enhance wound healing. There is strong scientific evidence to suggest that zinc may help manage or reduce symptoms of sickle cell anemia. Most of these studies reported increased height, weight, immune system function, and testosterone levels, as well as decreased numbers of crises and sickle cell formation following zinc treatment.
Zinc is regarded as a relatively safe and generally well-tolerated therapy when taken at recommended doses, and few studies report side effects. The recommended daily dose for adult and teenage males is 15 milligrams. The recommended daily dose for adult and teenage females is 12 milligrams. The recommended daily dose for pregnant females is 15 milligrams and 16-19 milligrams is recommended for breastfeeding females. The recommended daily dose for children ages 4-10 is 10 milligrams, and 5-10 milligrams is recommended for children 0-3 years old. Zinc acetate should only be used during pregnancy or breastfeeding if recommended by the patient's healthcare provider.
Unclear or conflicting scientific evidence:
Antineoplastons:Antineoplastons are a group of naturally occurring peptide fractions that have been studied for the treatment of various cancers, though antineoplaston therapy is not approved by the U.S. Food and Drug Administration (FDA). In recent years, antineoplastons have also been suggested as treatment for other conditions such as sickle cell anemia and thalassemia, but there is a lack of sufficient evidence from high-quality studies to support the use of antineoplastons for the treatment of sickle cell disease.
Avoid if allergic or hypersensitive to antineoplastons. Use cautiously with high risk of medical or psychiatric disorders, an active infection due to a possible decrease in white blood cells, high blood pressure, heart conditions, chronic obstructive pulmonary disease, liver disease/damage, or kidney disease/damage. Avoid if pregnant or breastfeeding.
Art therapy: Art therapy involves many forms of art to treat anxiety, depression, and other mental and emotional problems. Art therapy became a mental health profession in the 1930s. Today, it is practiced in hospitals, clinics, and community centers. There is some evidence suggesting that children with SCD may have improved coping ability and reduced healthcare visits following art therapy. More studies are needed to verify this.
Because art therapy may provoke distressing thoughts or feelings, it should be used under the guidance of a qualified art therapist or mental health professional. Related materials, such as turpentine or mineral spirits, should be used in areas with good ventilation because they release potentially toxic fumes.
L-Carnitine: The human body produces L-carnitine in the liver, kidney, and brain. Early evidence suggests the absence of any therapeutic effect of propionyl-L-carnitine for sickle cell disease. Additional studies are required before a firm recommendation can be made.
Avoid if allergic to L-carnitine. Use cautiously with peripheral vascular disease, high blood pressure, alcohol-induced liver cirrhosis, or diabetes. Use cautiously in low birth weight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.
Prayer, distant healing: Prayer can be defined as a "reverent petition," the act of asking for something while aiming to connect with God or another object of worship. Prayer has been studied as a coping mechanism for patients with sickle cell disease, with mixed results.
Prayer is not recommended as the sole treatment approach for potentially serious medical conditions and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Sometimes religious beliefs come into conflict with standard medical approaches and require an open dialog between patients and caregivers.
Vitamin B12: Vitamin B12 is a water-soluble vitamin that is commonly found in many foods, including fish, shellfish, meats, and dairy products. One study suggests that a practical daily combination may include folic acid, vitamin B12, and vitamin B6. This combination may be a simple and relatively inexpensive way to reduce sickle cell anemia patients' inherently high risk of endothelial damage. Further research is needed to confirm these results.
Vitamin B12 is generally considered safe when taken in amounts that do not exceed the Recommended Dietary Allowance (RDA). Avoid vitamin B12 supplements if allergic to cobalamin, cobalt, or any other product ingredients. Avoid with coronary stents or Leber's disease. Use cautiously if undergoing angioplasty.
Strong negative scientific evidence:
Urine therapy: Urine therapy refers to using one's own urine to maintain health, to prevent or cure sickness, to enhance beauty, or to promote meditation and spiritual enlightenment. Urine has been ingested, injected, or applied topically. Some evidence suggests that urea, which is found in urine, may help prevent and treat sickle cell crises in addition to helping eliminate complications. However, there is no definitive evidence from clinical studies to support the use of urine or urea in the treatment of sickle cell anemia. Additional study is needed in this area. Urine therapy should not be used in children or in women who are pregnant or breastfeeding. Side effects of urine therapy may include diarrhea, itch, pain, fatigue, soreness, and fever.
Traditional or theoretical uses which lack sufficient evidence:
Prevention
General: Because sickle cell disease (SCD) is an inherited condition, there is currently no known way to prevent the disease. However, a number of options are available for parents with family histories of SCD.
Genetic testing and counseling: Individuals who have SCD may meet with genetic counselors to discuss the risks of having children with the disease. Individuals from high-risk populations, or those with family histories of SCD, may meet with genetic counselors to determine whether they carry the SCD trait. Carriers can be determined through detailed family histories or genetic testing.
Known carriers of SCD may undergo genetic counseling before they conceive a child. Genetic counselors can explain the options and the associated risks of various tests, including pre-implantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).
Pre-implantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the SCD trait and only the embryos that are free of the SCD mutations may be implanted. SCD may be detected in an unborn baby. Genetic counselors may assist parents with difficult decisions.
Preventing complications of SCD: Individuals with SCD may meet with healthcare providers to discuss ways to prevent complications of SCD, such as routine vaccinations and eye exams.
Routine vaccinations may prevent some infections in patients with SCD, particularly young children and infants. Routine vaccinations are recommended. Additional vaccinations may also be recommended, such as an annual influenza (flu) vaccine beginning at six months of age, a pneumococcal vaccine at ages two and five, and the meningococcal vaccine (which protects against meningitis) at age five.
Routine eye examinations are advised, as vision problems may result when the vessels in the back of the eye become blocked. Laser surgery may be used to correct eye problems and prevent vision loss.
Author information
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
Bibliography
American Sickle Cell Anemia Association. .
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.
Gladwin MT, Sachdev V, Jison ML, et al. 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.
Lab Tests Online. .
Powars DR, Chan LS, Hiti A, et al. Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore). 2005 Nov;84(6):363-76.
Schnog JB, Duits AJ, Muskiet FA, et al. Sickle cell disease; a general overview. Neth J Med. 2004 Nov;62(10):364-74. Review.
Serjeant GR. The emerging understanding of sickle cell disease. Br J Haematol. 2001 Jan;112(1):3-18. Review.
Sickle Cell Disease Association of America. .
Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004 Oct 9;364(9442):1343-60. Review.
Vichinsky E. New therapies in sickle cell disease. Lancet. 2002 Aug 24;360(9333):629-31. Review.
Causes
The disorders collectively referred to as sickle cell disease (SCD) are caused by mutations, or genetic errors, which affect the structure of hemoglobin.
Hemoglobin is a protein in red blood cells that carries oxygen. It is made of four components: two alpha-globin subunits and two beta-globin subunits. The mutations that cause the most common form of SCD, sickle cell anemia (SCA), occur in the HBB gene. This gene contains the genetic instructions for making the beta-globin subunit of hemoglobin.
Normal red blood cells are round, flexible, and able to travel easily though blood vessels. In SCD, two normal alpha-globin subunits associate with two mutated beta-globin subunits and the resulting hemoglobin is defective.
Defects in hemoglobin may cause red blood cells to become stiff and sickle-shaped. These irregularly shaped blood cells do not flow as easily as normal red blood cells and often block blood flow and form blood clots.
In SCA, the HBB mutations produce a defective form of hemoglobin called hemoglobin S (HbS).
Other mutations in the HBB gene can produce different defective forms of hemoglobin, including hemoglobin C (HbC) and hemoglobin E (HbE). Different variations of SCD can result from combinations of mutations that affect hemoglobin.
Other defects in the HBB gene can result in abnormal levels of beta-globin. A type of SCD called beta-thalassemia results from abnormally low levels of beta-globin.
SCD is a recessive genetic condition, meaning that the mutations must be inherited from both parents for the disease to manifest. People who have inherited the mutation from only one parent may not have noticeable symptoms of the disease because only some of their red blood cells are defective. However, these people are called "carriers" of the SCD trait because they may pass the mutation to their children.
Risk factors
Sickle cell disease (SCD) is a group of inherited disorders in which hemoglobin, the protein in red blood cells that carries oxygen, is defective. SCD is caused by mutations (errors) in the HBB gene, which contains the genetic instructions for making beta-globin (a component of hemoglobin). Individuals with a family history of SCD have a higher risk of developing the disorder.
SCD is a recessive genetic disorder. Therefore, a person must inherit two copies of the genetic mutation (one copy from each parent) to develop SCD. People who inherit a mutation from only one parent are called "carriers" of the SCD trait and they may pass the mutation to their children.
If one parent carries the SCD trait, or only has one copy of the mutated gene, then each child has a 50% chance of inheriting one mutated gene and of being a carrier. If both parents are carriers, each child has a 25% chance of inheriting two mutated genes, a 50% chance of inheriting only one mutation, and a 25% chance of inheriting neither of the mutations. Thus, if both parents are carriers, approximately one out of every four children will have SCD.
If one parent has SCD and the other parent does not carry the trait, then all of the children will be carriers. If one parent has SCD and the other parent is a carrier, then each child has a 50% chance of having SCD and a 50% chance of being a carrier. If both parents have SCD, then all of their children will also have SCD.
Certain populations have higher frequencies of SCD carriers. As a result, these populations are also at higher risk of having SCD. Carrier frequency of SCD is especially high among African Americans. About 10% of African Americans carry the SCD trait and about one out of every 400 have the disease. Carrier frequency is lower (about 1%) in Hispanic Americans. Only one out of every 1,000-1,400 Hispanic Americans has SCD.
For carriers of SCD and other inherited genetic disorders, resources such as genetic testing and counseling may help them to evaluate their risks of having children with SCD.
Types of the disease
General: Sickle cell disease (SCD) is a common name for several inherited disorders that affect red blood cells. These disorders are caused by mutations in the HBB gene, which affect the beta-globin component of hemoglobin. Other mutations can lead to variants of hemoglobin such as hemoglobin C (HbC) and hemoglobin E (HbE). In SCD, at least one beta-globin subunit is replaced with HbS. The remaining beta-globin subunits may have mutations that result in other forms of SCD, such as beta thalassemia.
Sickle cell anemia (SCA): Sickle cell anemia (SCA), or SS disease, is the most common form of SCD. In SCA, the defective form of hemoglobin is called hemoglobin S (HbS). Both beta-globin subunits must have the same mutation to form HbS. The terms "sickle cell anemia" and "sickle cell disease" are often used interchangeably.
Other types:
Sickle-hemoglobin C (HbSC): If one HbS subunit is combined with one HbC subunit, the resulting disorder is called sickle-hemoglobin C (HbSC) disease.
Sickle-hemoglobin E (HbSE): If one HbS subunit is combined with one HbE subunit, the resulting disorder is called sickle-hemoglobin E (HbSE) disease.
Beta thalassemia: Mutations that result in abnormally low levels of hemoglobin cause a condition known as beta thalassemia. Mild forms of thalassemia are commonly called beta-plus thalassemia, while severe forms are often referred to as beta-zero-thalassemia.
If one HbS subunit is combined with one beta-globin subunit that contains a mutation that causes beta thalassemia, the resulting disorder is called hemoglobin S-beta thalassemia (HbSBetaThal) disease.