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Thalassemia describes a group of inherited disorders characterized by reduced or absent amounts of hemoglobin, the oxygen-carrying protein inside the red blood cells. There are two basic groups of thalassemia disorders: alpha thalassemia and beta thalassemia. These conditions cause varying degrees of anemia, which can range from insignificant to life threatening.
All types of thalassemias are considered quantitative diseases of hemoglobin, because the quantity of hemoglobin produced is reduced or absent. Usual adult hemoglobin is made up of three components: alpha globin, beta globin, and heme. Thalassemias are classified according to the globin that is affected, hence the names alpha and beta thalassemia. Although both classes of thalassemia affect the same protein, the alpha and beta thalassemias are distinct diseases that affect the body in different ways.
Beta thalassemia may be the most best-known type of thalassemia and is also called Cooley's anemia. It is caused by a change in the gene for the beta globin component of hemoglobin. Beta thalassemia causes variable anemia that can range from moderate to severe, depending in part on the exact genetic change underlying the disease. Beta thalassemia can be classified based on clinical symptoms. Beta thalassemia major usually causes severe anemia that can occur within months after birth. If left untreated, severe anemia can result in insufficient growth and development, as well as other common physical complications that can lead to a dramatically decreased life-expectancy. Fortunately, in developed countries beta thalassemia is usually identified by screening in the newborn period, before symptoms have developed. Children who are identified early can be started on ongoing blood transfusion therapy as needed. Although transfusion therapy prevents many of the complications of severe anemia, the body is unable to eliminate the excess iron contained in the transfused blood. Over time, the excess iron deposits in tissues and organs, resulting in damage and organ failure. Another medication must be administered to help the body eliminate the excess iron and prevent iron-over-load complications. Beta thalassemia intermedia describes the disease in individuals who have moderate anemia that only requires blood transfusions intermittently, if at all.
Alpha thalassemia is the result of changes in the genes for the alpha globin component of hemoglobin. There are two main types of alpha thalassemia disease: hemoglobin H disease and alpha thalassemia major. The two diseases are quite different from beta thalassemia as well as from one another. Individuals with hemoglobin H disease can experience events of hemolytic anemia—anemia caused by the rapid breakdown of the red blood cells. These events are thought to be triggered by various environmental causes, such as infection and/or exposure to certain chemicals. Hemoglobin H disease is in most cases milder than beta thalassemia. It does not generally require transfusion therapy. Alpha thalassemia major is a very serious disease that results in severe anemia that begins even before birth. Most affected babies do not survive to be born or die shortly after birth.
The thalassemias are among the most common genetic diseases worldwide. Both alpha and beta thalassemia have been described in individuals of almost every ancestry, but the conditions are more common among certain ethnic groups. Unaffected carriers of all types of thalassemia traits do not experience health problems. In fact, the thalassemia trait is protective against malaria, a disease caused by blood-borne parasites transmitted through mosquito bites. According to a widely accepted theory, most genetic changes—mutations—that cause thalassemia occurred multiple generations ago. Coincidentally, these mutations increased the likelihood that carriers would survive malaria infection. Survivors passed the mutation onto their offspring, and the trait became established throughout areas where malaria is common. As populations migrated, so did the thalassemia traits.
Beta thalassemia trait is seen most commonly in people with the following ancestry: Mediterranean (including North African, and particularly Italian and Greek), Middle Eastern, Indian, African, Chinese, and Southeast Asian (including Vietnamese, Laotian, Thai, Singaporean, Filipino, Cambodian, Malaysian, Burmese, and Indonesian). Alpha-thalassemia trait is seen with increased frequency in the same ethnic groups. However, there are different types of alpha thalassemia traits within these populations. The frequency of hemoglobin H disease and alpha thalassemia major depends on the type of alpha thalassemia trait. The populations in which alpha thalassemia diseases are most common include Southeast Asians and Chinese (particularly Southern Chinese).
It is difficult to obtain accurate prevalence figures for various types of thalassemia within different populations. This difficulty arises due to testing limitations in determining exact genetic diagnoses, as well as the fact that many studies have focused on small, biased hospital populations.
Two studies reflect prevalence figures that can be helpful counseling families and determining who to screen for beta thalassemia. Between the years of 1990 and 1996, the State of California screened more than 3.1 million infants born in the state for beta thalassemia. Approximately 1 in 114,000 infants had beta thalassemia major, with prevalence rates being highest among Asian Indians (about one in 4,000), Southeast Asians (about one in 10,000), and Middle Easterners (about one in 7,000). Another type of beta thalassemia disease, E/beta thalassemia, was represented in approximately one in 110,000 births, all of which occurred in families of Southeast Asian ancestry. Among Southeast Asians, the prevalence of E/beta thalassemia was approximately one in 2,600 births. This is in keeping with the observation that hemoglobin E trait carrier rates are relatively high within the Southeast Asian population: 16% in a study of 768 immigrants to California, and up to 25% in some specific Southeast Asian populations such as Cambodians. While these California studies address some of the limitations of earlier population studies, the pattern observed in California is expected to be different in other areas of the United States and the world. For example, Italians are underrepresented in this population when compared to the population of the East Coast of the United States.
Determining prevalence figures for alpha thalassemia is even more difficult due to increased limitations in diagnostic testing. All types of alpha thalassemia disease are most common among people of Southeast Asian and Chinese descent, for reasons that become clearer with an understanding of the underlying genetics of alpha thalassemia. One study of 500 pregnant women in Northern Thailand estimated a frequency of one in 500 pregnancies affected by alpha thalassemia major, for example. Prevalence of alpha thalassemia disease is significantly lower in the United States primarily because of immigration patterns; although at least one state, California, has observed growing hemoglobin H disease incidence rates that are high enough to justify universal newborn screening for the condition.
Humans normally make several types of the oxygen-carrying protein hemoglobin. An individual's stage in development determines whether he or she makes primarily embryonic, fetal, or adult hemoglobins. All types of hemoglobin are made of three components: heme, alpha (or alpha-like) globin, and beta (or beta-like) globin. All types of thalassemia are caused by changes in either the alpha- or beta-globin gene. These changes cause little or no globin to be produced. The thalassemias are, therefore, considered quantitative hemoglobin diseases. All types of thalassemias are recessively inherited, meaning that a genetic change must be inherited from both the mother and the father. The severity of the disease is influenced by the exact thalassemia mutations inherited, as well as other genetic and environmental factors. There are rare exceptions, notably with beta thalassemia, where globin gene mutations exhibit a dominant pattern of inheritance in which only one gene needs to be altered in order to see disease expression. Scientists continue to study the causes. For instance, a new mutation for alpha-thalassemia was discovered for the first time among Iranian patients in 2004.
BETA-THALASSEMIA. Most individuals have two normal copies of the beta globin gene, which is located on chromosome 11 and makes the beta globin component of normal adult hemoglobin, hemoglobin A. There are approximately 100 genetic mutations that have been described that cause beta thalassemia, designated as either beta0 or beta + mutations. No beta globin is produced with a beta0 mutation, and only a small fraction of the normal amount of beta globin is produced with a beta + mutation.
When an individual has one normal beta globin gene and one with a beta thalassemia mutation, he or she is said to carry the beta thalassemia trait. Beta thalassemia trait, like other hemoglobin traits, is protective against malaria infection. Trait status is generally thought not to cause health problems, although some women with beta thalassemia trait may have an increased tendency toward anemia during pregnancy.
When two members of a couple carry the beta thalassemia trait, there is a 25% chance that each of their children will inherit beta thalassemia disease by inheriting two beta thalassemia mutations, one from each parent. The clinical severity of the beta thalassemia disease—whether an individual has beta thalassemia intermedia or beta thalassemia major—will depend largely on whether the mutations inherited are beta0 thalassemia or beta + thalassemia mutations. Two beta0 mutations generally lead to beta thalassemia major, and two beta+ thalassemia mutations generally lead to beta thalassemia intermedia. Inheritance of one beta0 and one beta + thalassemia mutation tends to be less predictable.
Although relatively uncommon, there are other thalassemia-like mutations that can affect the beta globin gene. Hemoglobin E is the result of a substitution of a single nucleotide. This change results in a structurally altered hemoglobin that is produced in decreased amounts. Therefore, hemoglobin E is unique in that it is both a quantitative (i.e. thalassemia-like) and qualitative trait. When co-inherited with a beta thalassemia trait, it causes a disease that is almost indistinguishable from beta thalassemia disease. Large deletions around and including the beta globin gene can lead to delta/beta thalassemia or hereditary persistence of fetal hemoglobin (HPFH). Interestingly, delta/beta thalassemia trait behaves very similarly to beta thalassemia trait in its clinical manifestations. However, HPFH trait does not tend to cause hemoglobin disease when co-inherited with a second thalassemia or other beta globin mutation.
ALPHA-THALASSEMIA. Most individuals have four normal copies of the alpha globin gene, two copies on each chromosome 16. These genes make the alpha globin component of normal adult hemoglobin, which is called hemoglobin A. Alpha globin is also a component of fetal hemoglobin and the other major adult hemoglobin called hemoglobin A2. Mutations of the alpha globin genes are usually deletions of the gene, resulting in absent production of alpha globin. Since there are four genes (instead of the usual two) to consider when looking at alpha globin gene inheritance, there are several alpha globin types that are possible.
Absence of one alpha globin gene leads to a condition known as silent alpha thalassemia trait. This condition causes no health problems and can be detected only by special genetic testing. Alpha thalassemia trait occurs when two alpha globin genes are missing. This can occur in two ways. The genes may be deleted from the same chromosome, causing the 'cis' type of alpha thalassemia trait. Alternately, they may be deleted from different chromosomes, causing the 'trans' type of alpha thalassemia trait. In both instances, there are no associated health problems, although the trait status may be detected by more routine blood screening.
Hemoglobin H disease results from the deletion of three alpha globin genes, such that there is only one functioning gene. Typically, this can occur when one parent carries the silent alpha thalassemia trait, and the other parent carries the 'cis' type of the alpha thalassemia trait. In this situation, there is a 25% chance for hemoglobin H disease in each of such a couple's children.
Hemoglobin H disease-like symptoms can also be a part of a unique condition called alpha thalassemia mental retardation syndrome. Alpha thalassemia mental retardation syndrome can be caused by a deletion of a significant amount of chromosome 16, affecting the alpha globin genes. This is usually not inherited, but rather occurs sporadically in the affected individual. Affected individuals have mild hemoglobin H disease, mild-to-moderate mental retardation, and characteristic facial features. This syndrome can also occur as a sex-linked form in which a mutation is inherited in a particular gene on the X-chromosome. This gene influences alpha globin production, as well as various other developmental processes. Individuals affected with this form of the syndrome tend to have more severe mental retardation, delayed development, nearly absent speech, characteristic facial features, and genital-urinary abnormalities. The remaining discussion will focus only on aspects of hemoglobin H disease.
Alpha thalassemia major results from the deletion of all four alpha globin genes, such that there are no functioning alpha globin genes. This can occur when both parents carry the 'cis' type of the alpha thalassemia trait. In this situation, there is a 25% chance for alpha thalassemia major in each of such a couple's children.
Beta thalassemia major is characterized by severe anemia that can begin months after birth. In the United States and other developed countries beta thalassemia is identified and treated early and effectively. Therefore, the following discussion of symptoms applies primarily to affected individuals in the past and unfortunately in some underdeveloped countries now. If untreated, beta thalassemia major can lead to severe lethargy, paleness, and delays in growth and development. The body attempts to compensate by producing more blood, which is made inside the bones in the marrow. However, this is ineffective without the needed genetic instructions to make enough functioning hemoglobin. Instead, obvious bone expansion and changes occur that cause characteristic facial and other changes in appearance, as well as increased risk of fractures. Severe anemia taxes other organs in the body—such as the heart, spleen, and liver—which must work harder than usual. This can lead to heart failure, as well as enlargement and other problems of the liver and spleen. When untreated, beta thalassemia major generally results in childhood death, usually due to heart failure. In 2004, the first known heart attack associated with beta thalassemia major was reported. Fortunately, in developed countries diagnosis is usually made early, often before symptoms have begun. This allows for treatment with blood transfusion therapy, which can prevent most of the complications of the severe anemia caused by beta thalassemia major. Individuals with beta thalassemia intermedia have a more moderate anemia that may only require treatment with transfusion intermittently, such as when infections occur and stress the body. As a person with beta thalassemia intermedia gets older, however, the need for blood transfusions may increase to the point that they are required on a regular basis. When this occurs their disease becomes more similar to beta thalassemia major. Other genetic and environmental factors can influence the course of the disease as well. For example, co-inheritance of one or two alpha thalassemia mutations can tend to ameliorate some of the symptoms of beta thalassemia disease, which result in part from an imbalance in the amount of alpha- and beta-globin present in the red blood cells.
Hemoglobin h disease
Absence of three alpha globin genes causes an imbalance of alpha and beta globin proteins in the red blood cells. The excess beta globin proteins tend to come together to form hemoglobin H, which is unable to release oxygen to the tissues. In addition, hemoglobin H tends to precipitate out in the cells, causing damage to the red blood cell membrane. When affected individuals are exposed to certain drugs and chemicals known to make the membrane more fragile, the cells are thought to become vulnerable to breakdown in large numbers, a complication called hemolytic anemia. Fever and infection are also considered to be triggers of hemolytic anemia in hemoglobin H disease. This can result in fatigue, paleness, and a yellow discoloration of the skin and whites of eyes called jaundice. Usually, the anemia is mild enough not to require treatment. Severe anemia events may require blood transfusion, however, and are usually accompanied by such other symptoms as dark feces or urine and abdominal or back pain. These events are uncommon in hemoglobin H disease, although they occur more frequently in a more serious type of hemoglobin H disease called hemoglobin H/Constant Spring disease. Individuals effected with this type of hemoglobin H disease are also more likely to have enlargement of and other problems with the spleen.
Alpha thalassemia major
Because alpha globin is a necessary component of all major hemoglobins and some minor hemoglobins, absence of all functioning alpha globin genes leads to serious medical consequences that begin even before birth. Affected fetuses develop severe anemia as early as the first trimester of pregnancy. The placenta, heart, liver, spleen, and adrenal glands may all become enlarged. Fluid can begin collecting throughout the body as early as the start of the second trimester, causing damage to developing tissues and organs. Growth retardation is also common. Affected fetuses usually miscarry or die shortly after birth. In addition, women carrying affected fetuses are at increased risk of developing complications of pregnancy and delivery. Up to 80% of such women develop toxemia, a disturbance of metabolism that can potentially lead to convulsions and coma. Other maternal complications include premature delivery and increased rates of delivery by cesarean section, as well as hemorrhage after delivery.
Thalassemia may be suspected if an individual shows signs that are suggestive of the disease. In all cases, however, laboratory diagnosis is essential to confirm the exact diagnosis and to allow for the provision of accurate genetic counseling about recurrence risks and testing options for parents and affected individuals. Screening is likewise recommended to determine trait status for individuals of high-risk ethnic groups.
The following tests are used to screen for thalassemia disease and/or trait:
- complete blood count
- hemoglobin electrophoresis with quantitative hemoglobin A2 and hemoglobin F
- free erythrocyte-protoporphyrin (or ferritin or other studies of serum iron levels)
A complete blood count will identify low levels of hemoglobin, small red blood cells, and other red blood cell abnormalities that are characteristic of a thalassemia diagnosis. Since thalassemia trait can sometimes be difficult to distinguish from iron deficiency, tests to evaluate iron levels are important. A hemoglobin electrophoresis is a test that can help identify the types and quantities of hemoglobin made by an individual. This test uses an electric field applied across a slab of gel-like material. Hemoglobins migrate through this gel at various rates and to specific locations, depending on their size, shape, and electrical charge. Isoelectric focusing and high-performance liquid chromatography (HPLC) use similar principles to separate hemoglobins and can be used instead of or in various combinations with hemoglobin electrophoresis to determine the types and quantities of hemoglobin present. Hemoglobin electrophoresis results are usually within the normal range for all types of alpha thalassemia. However, hemoglobin A2 levels and sometimes hemoglobin F levels are elevated when beta thalassemia disease or trait is present. Hemoglobin electrophoresis can also detect structurally abnormal hemoglobins that may be co-inherited with a thalassemia trait to cause thalassemia disease (i.e., hemoglobin E) or other types of hemoglobin disease (i.e., sickle hemoglobin). Sometimes DNA testing is needed in addition to the above screening tests. This can be performed to help confirm the diagnosis and establish the exact genetic type of thalassemia.
Diagnosis of thalassemia can occur under various circumstances and at various ages. Several states offer thalassemia screening as part of the usual battery of blood tests done for newborns. This allows for early identification and treatment. Thalassemia can be identified before birth through the use of prenatal diagnosis. Chorionic villus sampling (CVS) can be offered as early as 10 weeks of pregnancy and involves removing a sample of the placenta made by the baby and testing the cells. CVS carries a risk of causing a miscarriage that is between 0.5%-1%. Amniocentesis is generally offered between 15 and 22 weeks of pregnancy, but can sometimes be offered earlier. Two to three tablespoons of the fluid surrounding the baby is removed. This fluid contains fetal cells that can be tested. The risk of miscarriage associated with amniocentesis ranges from 0.33-0.5%. Pregnant woman and couples may choose prenatal testing in order to prepare for the birth of a baby that may have thalassemia. Alternately, knowing the diagnosis during pregnancy allows for the option of pregnancy termination. Preimplantation genetic diagnosis (PGD) is a relatively new technique that involves in-vitro fertilization followed by genetic testing of one cell from each developing embryo. Only the embryos unaffected by sickle cell disease are transferred back into the uterus. PGD is currently available on a research basis only and is relatively expensive.
Individuals with beta thalassemia major receive regular blood transfusions, usually on a monthly basis. This helps prevent severe anemia and allows for more normal growth and development. Transfusion therapy does have limitations, however. Individuals can develop reactions to certain proteins in the blood—called a transfusion reaction. This can make locating appropriately matched donor blood more difficult. Although blood supplies in the United States are very safe, particularly relative to the past and to other areas of the world, there remains an increased risk of exposure to such blood-borne infections as hepatitis. Additionally, the body is not able to get rid of the excess iron that accompanies each transfusion. An additional medication called desferoxamine is administered, usually five nights per week over a period of several hours, using an automatic pump that can be used during sleep or taken anywhere the person goes. This medication is able to bind to the excess iron, which can then be eliminated through urine. If desferoxamine is not used regularly or is unavailable, iron overload can develop and cause tissue damage and organ damage and failure. The heart, liver, and endocrine organs are particularly vulnerable. Desferoxamine itself may rarely produce allergic or toxic side effects, including hearing damage. Signs of desferoxamine toxicity are screened for and generally develop in individuals who overuse the medication when body iron levels are sufficiently low. Overall, however, transfusion and desferoxamine therapy have increased the life expectancy of individuals with the most severe types of beta thalassemia major to the 4th or 5th decade. This can be expected to improve with time and increased developments in treatment, as well as for those with more mild forms of the disease.
New treatments offer additional options for some individuals with beta thalassemia major. There are various medications that target the production of red blood cells (i.e. erythropoeitin) or fetal hemoglobin (i.e. hydroxyurea and butyrate). Their effectiveness in ameliorating the severity of beta thalassemia is currently being investigated. Another promising new treatment is bone marrow transplantation, in which the bone marrow of an affected individual is replaced with the bone marrow of an unaffected donor. If successful, this treatment can provide a cure. However, there is an approximately 10-15% chance the procedure could be unsuccessful (i.e. the thalassemia returns); result in complications (i.e. graft-versus-host disease); or result in death. The risk for specific individuals depends on current health status, age, and other factors. Because of the risks involved and the fact that beta thalassemia is a treatable condition, transplant physicians require a brother or sister donor who has an identically matched tissue type, called HLA type. HLA type refers to the unique set of proteins present on each individual's cells, which allows the immune system to recognize "self" from "foreign." HLA type is genetically determined, so there is a 25% chance for two siblings to be a match. Transplant physicians and researchers are also investigating ways to improve the safety and effectiveness of bone marrow transplantation. Using newborn sibling umbilical cord blood—the blood from the placenta that is otherwise discarded after birth but contains cells that can go on to make bone marrow—seems to provide a safer and perhaps more effective source of donor cells. Donors and recipients may not have to be perfect HLA matches for a successful transplant using cord blood cells. Trials are also underway to determine the effectiveness of "partial transplants," in which a safer transplant procedure is used to replace only a percentage of the affected individual's bone marrow. Other possible treatments on the horizon may include gene therapy techniques aimed at increasing the amount of normal hemoglobin the body is able to make.
Hemoglobin h disease
Hemoglobin H disease is a relatively mild form of thalassemia that may go unrecognized. It is not generally considered a condition that will reduce one's life expectancy. Education is an important part of managing the health of an individual with hemoglobin H disease. It is important to be able to recognize the signs of severe anemia that require medical attention. It is also important to be aware of the medications, chemicals, and other exposures to avoid due to the theoretical risk they pose of causing a severe anemia event. When severe anemia occurs, it is treated with blood transfusion therapy. For individuals with hemoglobin H disease, this is rarely required. For those with the hemoglobin H/Constant Spring form of the disease, the need for transfusions may be intermittent or ongoing, perhaps on a monthly basis and requiring desferoxamine treatment. Individuals with this more severe form of the disease may also have an increased chance of requiring removal of an enlarged and/or overactive spleen.
Anemia — A blood condition in which the level of hemoglobin or the number of red blood cells falls below normal values. Common symptoms include paleness, fatigue, and shortness of breath.
Bilirubin — A yellow pigment that is the end result of hemoglobin breakdown. This pigment is metabolized in the liver and excreted from the body through the bile. Bloodstream levels are normally low; however, extensive red cell destruction leads to excessive bilirubin formation and jaundice.
Bone marrow — A spongy tissue located in the hollow centers of certain bones, such as the skull and hip bones. Bone marrow is the site of blood cell generation.
Bone marrow transplantation — A medical procedure used to treat some diseases that arise from defective blood cell formation in the bone marrow. Healthy bone marrow is extracted from a donor to replace the marrow in an ailing individual. Proteins on the surface of bone marrow cells must be identical or very closely matched between a donor and the recipient.
Desferoxamine — The primary drug used in iron chelation therapy. It aids in counteracting the life-threatening buildup of iron in the body associated with long-term blood transfusions.
Globin — One of the component protein molecules found in hemoglobin. Normal adult hemoglobin has a pair each of alpha-globin and beta-globin molecules.
Heme — The iron-containing molecule in hemoglobin that serves as the site for oxygen binding.
Hemoglobin — Protein-iron compound in the blood that carries oxygen to the cells and carries carbon dioxide away from the cells.
Hemoglobin A — Normal adult hemoglobin that contains a heme molecule, two alpha-globin molecules, and two beta-globin molecules.
Hemoglobin electrophoresis — A laboratory test that separates molecules based on their size, shape, or electrical charge.
Hepatomegaly — An abnormally large liver.
HLA type — Refers to the unique set of proteins called human leukocyte antigens. These proteins are present on each individual's cell and allow the immune system to recognize 'self' from 'foreign'. HLA type is particularly important in organ and tissue transplantation.
Hydroxyurea — A drug that has been shown to induce production of fetal hemoglobin. Fetal hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of adult hemoglobin. Higher-than-normal levels of fetal hemoglobin can ameliorate some of the symptoms of thalassemia.
Iron overload — A side effect of frequent blood transfusions in which the body accumulates abnormally high levels of iron. Iron deposits can form in organs, particularly the heart, and cause life-threatening damage.
Jaundice — Yellowing of the skin or eyes due to excess of bilirubin in the blood.
Mutation — A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease, and can be transmitted to offspring.
Placenta — The organ responsible for oxygen and nutrition exchange between a pregnant mother and her developing baby.
Red blood cell — Hemoglobin-containing blood cells that transport oxygen from the lungs to tissues. In the tissues, the red blood cells exchange their oxygen for carbon dioxide, which is brought back to the lungs to be exhaled.
Screening — Process through which carriers of a trait may be identified within a population.
Splenomegaly — Enlargement of the spleen.
Alpha thalassemia major
Because alpha thalassemia major is most often a condition that is fatal in the prenatal or newborn period, treatment has previously been focused on identifying affected pregnancies in order to provide appropriate management to reduce potential maternal complications. Pregnancy termination provides one form of management. Increased prenatal surveillance and early treatment of maternal complications is an approach that is appropriate for mothers who wish to continue their pregnancy with the knowledge that the baby will most likely not survive. In recent years, there have been a handful of infants with this condition who have survived long-term. Most of these infants received experimental treatment including transfusions before birth, early delivery, and even bone marrow transplantation before birth, although the latter procedure has not yet been successful. For those infants that survive to delivery, there seems to be an increased risk of developmental problems and physical effects, particularly heart and genital malformations. Otherwise, their medical outlook is similar to a child with beta thalassemia major, with the important exception that ongoing, life-long blood transfusions begin right at birth.
As discussed above, the prognosis for individuals with the most serious types of thalassemia has improved drastically in the last several years following recent medical advances in transfusion, chemo-, and transplantation therapy. Advances continue and promise to improve the life expectancy and quality of life further for affected individuals.
"First Known Heart Attack Associated With Beta-thalassemia Major Reported." Heart Disease Weekly February 22, 2004: 10.
"Novel Alpha-thalassemia Mutations Identified." Hematology Week January 26, 2004: 19.
Children's Blood Foundation. 333 East 38th St., Room 830, New York, NY 10016-2745. (212) 297-4336. firstname.lastname@example.org.
Cooley's Anemia Foundation, Inc. 129-09 26th Ave. #203, Flushing, NY 11354. (800) 522-7222 or (718) 321-2873. http://www.thalassemia.org.
March of Dimes Birth Defects Foundation. 1275 Mamaroneck Ave., White Plains, NY 10605. (888) 663-4637. email@example.com. http://www.modimes.org.
National Heart, Lung, and Blood Institute. PO Box 30105, Bethseda, MD 20824-0105. (301) 592-8573. firstname.lastname@example.org. http://www.nhlbi.nih.gov.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. http://www.rarediseases.org.
Bojanowski J. "Alpha Thalassemia Major: The Possibility of Long-Term Survival." Pamphlet from the Northern California Comprehensive Thalassemia Center. (1999).
Children's Hospital Oakland, Northern California Comprehensive Thalassemia Center website. http://www.thalassemia.com.
Cooley's Anemia Foundation, Inc. website. http://www.thalassemia.org/gohome.html.
Joint Center for Sickle Cell and Thalassemic Disorders website. http://cancer.mgh.harvard.edu/medOnc/sickle.htm.
Gale Encyclopedia of Medicine. Copyright 2008 The Gale Group, Inc. All rights reserved.
a heterogeneous group of hereditary hemolytic anemias marked by a decreased rate of synthesis of one or more hemoglobin polypeptide chains, classified according to the chain involved (α, β, δ); the two major categories are α- and β-thalassemia.
α-thalassemia (alpha-thalassemia) that caused by diminished synthesis of alpha chains of hemoglobin. The homozygous form is incompatible with life, the stillborn infant displaying severe hydrops fetalis. The heterozygous form may be asymptomatic or marked by mild anemia.
β-thalassemia (beta-thalassemia) that caused by diminished synthesis of beta chains of hemoglobin. The homozygous form is called t. major and the heterozygous form is called t. minor.
thalassemia ma´jor the homozygous form of β-thalassemia, in which hemoglobin A is completely absent; it appears in the newborn period and is marked by hemolytic, hypochromic, microcytic anemia; hepatosplenomegaly; skeletal deformation; mongoloid facies; and cardiac enlargement.
thalassemia mi´nor the heterozygous form of β-thalassemia; it is usually asymptomatic, but there may be mild anemia.
sickle cell–thalassemia a hereditary anemia involving simultaneous heterozygosity for hemoglobin S and thalassemia.
Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved.
thal·as·se·mi·a, thalassanemia (thal'ă-sē'mē-ă, thă-las-ă-nē'mē-ă),
Any of a group of inherited disorders of hemoglobin metabolism in which there is impaired synthesis of one or more of the polypeptide chains of globin; several genetic types exist, and the corresponding clinical picture may vary from barely detectable hematologic abnormality to severe and fatal anemia.
[G. thalassa, the sea, + haima, blood]
Farlex Partner Medical Dictionary © Farlex 2012
An inherited form of anemia occurring chiefly among people of Mediterranean descent, caused by faulty synthesis of part of the hemoglobin molecule. Also called Mediterranean anemia.
The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved.
thalassemiaBeta thalassemia, clinical thalassemia, Cooley's anemia, Mediterranean anemia, thalassemia major Hematology A group of genetic diseases by underproduction of hemoglobin due to mutations in the beta globin gene, which is more common in Mediterraneans Heredity Parents are carriers–heterozygotes; one in 4 children is homozygous for the mutation and thus has full-blown disease Clinical See Anemia. Cf Sickle cell anemia.
α-thalassemiaHemoglobin Barts Hematology An inherited condition caused by a defect in the synthesis of the Hb α chain; Hb Barts hemoglobinopathy is characterized by the presence of 4 gamma chains; it is more common in southeast Asians; the most severe form of alpha thalassemia causes stillbirth due to hydrops fetalis Heredity Parents are carriers–heterozygotes; one in 4 children is homozygous for the mutation and thus has full-blown disease Clinical Pallor, fatiguability, FTT, fever, infections, diarrhea Management Transfusions
β-thalassemiaThalassemia major Hematology A hemoglobinopathy caused by a defect in the synthesis of Hb β chain Clinical Pallor, fatigability, FTT, fever due to infections, diarrhea, bone deformities, hepatosplenomegaly Management Transfusions, but iron overload can damage the heart, liver, and endocrine systems, ergo iron chelation–early use of deferiprone, deferoxamine ↓ transfusion-related iron overload and may protect against DM, cardiac disease, early death
δ-thalassemiaHematology A condition characterized by a defect of Hb A2–α2δ2; because Hb A2 comprises only 3% of the circulating Hb, even its complete absence; δ-thalassemia has little clinical or hematologic impact
γ-thalassemiaHematology A condition characterized by a defect of gamma–γ Hb chains found in Hb F–α2γ2; because Hb F is present primarily in the fetus and newborns, it is rarely seen outside of the neonatal period, but may cause transient neonatal hemolytic anemia.
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.
thal·as·se·mi·a, thalassanemia (thal'ă-sē'mē-ă, -ă-să-nē'mē-ă)
Any of a group of inherited disorders of hemoglobin metabolism in which there is impaired synthesis of one or more of the polypeptide chains of globin; several genetic types exist, and the corresponding clinical picture may vary from barely detectable hematologic abnormality to severe and fatal anemia. People of Mediterranean, extraction are more often affected than others by this type of anemia.
Synonym(s): thalassaemia, thalassanaemia.
Synonym(s): thalassaemia, thalassanaemia.
[G. thalassa, the sea, + haima, blood]
Medical Dictionary for the Health Professions and Nursing © Farlex 2012
thal·as·se·mi·a, thalassanemia (thal'ă-sē'mē-ă, -ă-să-nē'mē-ă)
Any of a group of inherited disorders of hemoglobin metabolism with impaired synthesis of one or more polypeptide chains of globin; several genetic types exist.
Synonym(s): thalassaemia, thalassanaemia.
Synonym(s): thalassaemia, thalassanaemia.
[G. thalassa, the sea, + haima, blood]
Medical Dictionary for the Dental Professions © Farlex 2012