What Is ThalassemiaWhat Is Thalassemia??

Thalassemia is a group of inherited disorders of hemoglobin synthesis characterized by a reduced or absent output of one or more of the globin chains of adult hemoglobin .

The name is derived from the Greek words Thalasso = Sea" and "Hemia = Blood" in reference to anemia of the sea.

Reduction of α or β chain synthesis causes α or β-thalassaemia respectively.

What Is ThalassemiaWhat Is Thalassemia?? It is an inherited atuosomal recesive blood It is an inherited atuosomal recesive blood

disorder that causes mild or severe disorder that causes mild or severe anemia . . The anemia is due to reduced hemoglobin The anemia is due to reduced hemoglobin

and fewer red blood cells than normal. and fewer red blood cells than normal. Hemoglobin is the protein in red blood cells Hemoglobin is the protein in red blood cells

that carries oxygen to all parts of the body.that carries oxygen to all parts of the body.

In people with thalassemia, the In people with thalassemia, the genes that code for hemoglobin are genes that code for hemoglobin are missing or variant (different than the missing or variant (different than the normal genes). Severe forms of normal genes). Severe forms of thalassemia are usually diagnosed in thalassemia are usually diagnosed in early childhood and are lifelong early childhood and are lifelong conditions. conditions.

The two main types of thalassemiaThe two main types of thalassemia There are two types;There are two types; Alpha, Alpha, chain of Hgb I saffected, and chain of Hgb I saffected, and beta, beta, chain is affected (more common). chain is affected (more common). The genes for each type of thalassemia are passed The genes for each type of thalassemia are passed

from parents to their children. from parents to their children. Alpha and beta thalassemias can be classified into:Alpha and beta thalassemias can be classified into: Mild (minor/trait),Mild (minor/trait), Moderate (intermediate)Moderate (intermediate) and severe (major forms. and severe (major forms.

Alpha thalassemiaAlpha thalassemia occurs when one or more of the four genes occurs when one or more of the four genes

needed for making the alpha globin chain of needed for making the alpha globin chain of hemoglobin are variant or missing. Moderate hemoglobin are variant or missing. Moderate to severe anemia results when more than two to severe anemia results when more than two genes are affected. The most severe form of genes are affected. The most severe form of alpha thalassemia is known as alpha alpha thalassemia is known as alpha thalassemia major (incompatible with life). It thalassemia major (incompatible with life). It can result in miscarriage.can result in miscarriage.

Alpha ThalassemiasAlpha Thalassemias Alpha thalassemia Alpha thalassemia ““silent carriersilent carrier”” Mild alpha thalassemia, also called alpha Mild alpha thalassemia, also called alpha

thalassemia minor or alpha thalassemia trait thalassemia minor or alpha thalassemia trait Hemoglobin H disease Hemoglobin H disease Hydrops fetalis, or alpha thalassemia major Hydrops fetalis, or alpha thalassemia major

Beta thalassemia Beta thalassemia occurs when one or both of the two genes occurs when one or both of the two genes

needed for making the beta globin chain of needed for making the beta globin chain of hemoglobin are variant. hemoglobin are variant.

The severity of illness depends on whether one The severity of illness depends on whether one or both genes are affected and the nature of the or both genes are affected and the nature of the abnormality. If both genes are affected, anemia abnormality. If both genes are affected, anemia can range from moderate to severe. The severe can range from moderate to severe. The severe form of beta thalassemia is also known as form of beta thalassemia is also known as CooleyCooley’’s anemia. s anemia. Cooley’s anemia is the most is the most common severe form of thalassemia common severe form of thalassemia

Transmission of ß thalassemia

If a carrier (thalassemia minor) marries a non-carrier, on average half of their children will be carriers, but none will develop thalassemia major.

abdullah ali alqarni abdullah ali alqarni

Transmission ß of thalassemia- Cont

However if two carriers marry, in each pregnancy there is a 25% chance of a non-carrier child, a 50% chance of a carrier child (thalassemia minor), and a 25% chance of a child with thalassemia major.

abdullah ali alqarni abdullah ali alqarni

An example of inheritance:An example of inheritance:a carrier married to a normal persona carrier married to a normal person

Source :Emirates Thalassemia Societyabdullah ali alqarni abdullah ali alqarni

abdullah ali alqarni abdullah ali alqarni

An example of inheritanceAn example of inheritance- Cont:- Cont:marriage between two carriersmarriage between two carriers

Source: Emirates Thalassemia Societyabdullah ali alqarni abdullah ali alqarni

abdullah ali alqarni abdullah ali alqarni

abdullah ali alqarni abdullah ali alqarni

Thalassemia IntermediaThalassemia Intermedia.. Caused by the reduced availability of Caused by the reduced availability of

beta chains in hemoglobin andbeta chains in hemoglobin and

Types of Types of ßß thalassemia- Contthalassemia- Cont

abdullah ali alqarni abdullah ali alqarni

Beta ThalassemiasBeta Thalassemias Beta thalassemia minor, also called Beta thalassemia minor, also called

thalassemia minor or thalassemia trait. thalassemia minor or thalassemia trait. Such people usually practice normal life, but Such people usually practice normal life, but

may suffer from a mild form of anemia. may suffer from a mild form of anemia. Beta thalassemia intermedia, also called Beta thalassemia intermedia, also called

thalassemia intermedia or mild Cooleythalassemia intermedia or mild Cooley ’’s s anemia . Can lead to moderate to severe anemia . Can lead to moderate to severe anemia and an array of complications anemia and an array of complications including bone deformities and splenomegaly.including bone deformities and splenomegaly.

Beta thalassemia major, also called thalassemia Beta thalassemia major, also called thalassemia major or Cooleymajor or Cooley’’s anemia s anemia

Mediterranean anemia Mediterranean anemia Cooley’s anemia is another name for the severe is another name for the severe

form of beta thalassemia. form of beta thalassemia. The name is sometimes used to refer to any type The name is sometimes used to refer to any type

of thalassemia that requires treatment with regular of thalassemia that requires treatment with regular blood transfusions.leading to iron-overload which blood transfusions.leading to iron-overload which is treated with chelation therapy to prevent death is treated with chelation therapy to prevent death from organ failure.from organ failure.

If one gene is affected, a person is a carrier and If one gene is affected, a person is a carrier and has mild anemia. This condition is called beta has mild anemia. This condition is called beta thalassemia trait, or beta thalassemia minor. thalassemia trait, or beta thalassemia minor.

If both genes are variant, a person may have If both genes are variant, a person may have moderate anemia (beta thalassemia intermedia, or moderate anemia (beta thalassemia intermedia, or mild Cooleymild Cooley’’s anemia) or severe anemia (beta s anemia) or severe anemia (beta thalassemia major, or Cooleythalassemia major, or Cooley’’s anemia). s anemia).

CooleyCooley’’s anemia, or beta thalassemia major, is a s anemia, or beta thalassemia major, is a rare condition. A survey in 1993 found 518 rare condition. A survey in 1993 found 518 CooleyCooley’’s anemia patients in the United States. s anemia patients in the United States. Most of these persons had the severe form of the Most of these persons had the severe form of the illness, but there may be more who are not illness, but there may be more who are not diagnosed. diagnosed.

If two people with beta thalassemia trait (carriers) have a If two people with beta thalassemia trait (carriers) have a

baby, one of three things can happenbaby, one of three things can happen::

The baby could receive two normal genes (one from The baby could receive two normal genes (one from each parent) and have normal blood (1 in 4 chance, or each parent) and have normal blood (1 in 4 chance, or 25 percent). 25 percent).

The baby could receive one normal gene from one The baby could receive one normal gene from one parent and one variant gene from the other parent and parent and one variant gene from the other parent and have thalassemia trait (2 in 4 chance, or 50 percent). have thalassemia trait (2 in 4 chance, or 50 percent).

The baby could receive two thalassemia genes (one The baby could receive two thalassemia genes (one from each parent) and have a moderate to severe form from each parent) and have a moderate to severe form of the disease (1 in 4 chance, or 25 percent). of the disease (1 in 4 chance, or 25 percent).

What Are the Signs and Symptoms of What Are the Signs and Symptoms of ThalassemiaThalassemia??

The symptoms of thalassemia depend on the The symptoms of thalassemia depend on the type and severity of the disease. Symptoms type and severity of the disease. Symptoms occur when not enough oxygen gets to various occur when not enough oxygen gets to various parts of the body due to low hemoglobin and a parts of the body due to low hemoglobin and a shortage of red blood cells in the blood shortage of red blood cells in the blood (anemia). (anemia).

““Silent carriersSilent carriers”” and persons with alpha and persons with alpha thalassemia trait or beta thalassemia trait thalassemia trait or beta thalassemia trait (also called carriers) usually have no (also called carriers) usually have no symptoms. Those with alpha or beta symptoms. Those with alpha or beta thalassemia trait often have mild anemia thalassemia trait often have mild anemia that may be found by a blood test. that may be found by a blood test.

In In more severe types of thalassemia, such as Cooleymore severe types of thalassemia, such as Cooley’’s anemia, s anemia, signs of the severe anemia are seen in early childhood and signs of the severe anemia are seen in early childhood and

may includemay include:: 1.1. Fatigue (feeling tired) and weakness Fatigue (feeling tired) and weakness 2.2. Pale skin or jaundice (yellowing of the skin) Pale skin or jaundice (yellowing of the skin) 3.3. Protruding abdomen, with enlarged spleen Protruding abdomen, with enlarged spleen

and liver and liver 4.4. Dark urine Dark urine 5.5. Abnormal facial bones and poor growth Abnormal facial bones and poor growth

Babies with all four genes affected (a condition Babies with all four genes affected (a condition called alpha thalassemia major, or hydrops fetalis) called alpha thalassemia major, or hydrops fetalis) usually die before or shortly after birthusually die before or shortly after birth

How Is Thalassemia DiagnosedHow Is Thalassemia Diagnosed??

1.1. Thalassemia is diagnosed using blood tests, including a Thalassemia is diagnosed using blood tests, including a complete blood count (CBC) and special hemoglobin complete blood count (CBC) and special hemoglobin studies.studies.

2.2. A CBC provides information about the amount of A CBC provides information about the amount of hemoglobin and the different kinds of blood cells, such as hemoglobin and the different kinds of blood cells, such as red blood cells, in a sample of blood. People with red blood cells, in a sample of blood. People with thalassemia have fewer red blood cells than normal and thalassemia have fewer red blood cells than normal and less hemoglobin than normal in their blood. Carriers of less hemoglobin than normal in their blood. Carriers of the trait may have slightly small red blood cells as their the trait may have slightly small red blood cells as their only sign. only sign.

3.3. Hemoglobin studies measure the types of hemoglobin in a Hemoglobin studies measure the types of hemoglobin in a blood sample. blood sample.

CooleyCooley’’s anemias anemia

is usually diagnosed in early childhood because of is usually diagnosed in early childhood because of signs and symptoms, including severe anemia. signs and symptoms, including severe anemia. Some people with milder forms of thalassemia may Some people with milder forms of thalassemia may be diagnosed after a routine blood test shows that be diagnosed after a routine blood test shows that they have anemia. Doctors suspect thalassemia if a they have anemia. Doctors suspect thalassemia if a child has anemia and is a member of an ethnic child has anemia and is a member of an ethnic group that is at risk for thalassemia. group that is at risk for thalassemia.

To distinguish anemia caused by iron deficiency To distinguish anemia caused by iron deficiency from anemia caused by thalassemia, tests of the from anemia caused by thalassemia, tests of the amount of iron in the blood may be done. Iron-amount of iron in the blood may be done. Iron-deficiency anemia occurs because the body doesndeficiency anemia occurs because the body doesn ’’t t have enough iron for making hemoglobin. The have enough iron for making hemoglobin. The anemia in thalassemia occurs not because of a lack anemia in thalassemia occurs not because of a lack of iron, but because of a problem with either the of iron, but because of a problem with either the alpha globin chain or the beta globin chain of alpha globin chain or the beta globin chain of hemoglobin. Iron supplements do nothing to hemoglobin. Iron supplements do nothing to improve the anemia of thalassemia, because improve the anemia of thalassemia, because missing iron is not the problem. missing iron is not the problem.

Family genetic studies are also helpful in Family genetic studies are also helpful in diagnosing thalassemia. This involves diagnosing thalassemia. This involves taking a family history and doing blood taking a family history and doing blood tests on family members. tests on family members.

Prenatal testing can determine if an unborn Prenatal testing can determine if an unborn baby has thalassemia and how severe it is baby has thalassemia and how severe it is likely to be.likely to be.

How Is Thalassemia TreatedHow Is Thalassemia Treated??

Treatment for thalassemia depends on the type and severity Treatment for thalassemia depends on the type and severity of the disease. of the disease.

People who are carriers (they have thalassemia trait) People who are carriers (they have thalassemia trait) usually have no symptoms and need no treatment. usually have no symptoms and need no treatment.

Those with moderate forms of thalassemia (for example, Those with moderate forms of thalassemia (for example, thalassemia intermedia) may need blood transfusions thalassemia intermedia) may need blood transfusions occasionally, such as when they are experiencing stress occasionally, such as when they are experiencing stress due to an infection. If a person with thalassemia due to an infection. If a person with thalassemia intermedia worsens and needs regular transfusions, he or intermedia worsens and needs regular transfusions, he or she is no longer considered to have thalassemia she is no longer considered to have thalassemia intermedia; instead, the person is said to have thalassemia intermedia; instead, the person is said to have thalassemia major, or Cooleymajor, or Cooley’’s anemia. s anemia.

2-2-Iron Chelation TherapyIron Chelation Therapy Iron chelation therapy uses medicine to Iron chelation therapy uses medicine to

remove the excess iron that builds up in the remove the excess iron that builds up in the body when a person has frequent blood body when a person has frequent blood transfusions. If the iron is not removed, it transfusions. If the iron is not removed, it damages body organs, such as the heart and damages body organs, such as the heart and liver. liver.

The medicine, deferoxamine (deh-fer-ROX-uh-The medicine, deferoxamine (deh-fer-ROX-uh-meen), works best when given slowly under the meen), works best when given slowly under the skin, usually with a small portable pump skin, usually with a small portable pump overnight. This therapy is demanding and overnight. This therapy is demanding and sometimes is mildly painful, so some people sometimes is mildly painful, so some people stop chelation therapy. A pill form of iron stop chelation therapy. A pill form of iron chelation therapy, deferasirox, was approved in chelation therapy, deferasirox, was approved in November 2005 for use in the United States. November 2005 for use in the United States.

People who have iron overload should not take People who have iron overload should not take vitamins or other supplements that contain iron. vitamins or other supplements that contain iron.

33--SurgerySurgery Surgery may be needed if body organs, such as Surgery may be needed if body organs, such as

the spleen or gall bladder, are affected. For the spleen or gall bladder, are affected. For example, if the spleen becomes inflamed and example, if the spleen becomes inflamed and enlarged, it may be removed. If gallstones enlarged, it may be removed. If gallstones develop, the gall bladder may be removed. develop, the gall bladder may be removed.

A-A-Bone Marrow or Stem Cell Bone Marrow or Stem Cell TransplantsTransplants

Bone marrow or stem cell transplants have Bone marrow or stem cell transplants have been used successfully in some children with been used successfully in some children with severe thalassemia. This is a risky procedure, severe thalassemia. This is a risky procedure, but it offers a cure for those children who but it offers a cure for those children who qualify. qualify.

44--Other TreatmentsOther Treatments People with severe thalassemia are more likely People with severe thalassemia are more likely

to get infections that can worsen their anemia. to get infections that can worsen their anemia. They should get an annual flu shot and the They should get an annual flu shot and the pneumonia vaccine to help prevent infections. pneumonia vaccine to help prevent infections.

Folic acid is a B vitamin that helps build red Folic acid is a B vitamin that helps build red blood cells. People with thalassemia should blood cells. People with thalassemia should take folic acid supplements. take folic acid supplements.

Researchers are also studying other treatments, Researchers are also studying other treatments, such as gene therapy and fetal hemoglobin. such as gene therapy and fetal hemoglobin.

55--Gene therapyGene therapy

Someday, it may be possible to cure Someday, it may be possible to cure thalassemia in an unborn child by inserting a thalassemia in an unborn child by inserting a normal gene into the childnormal gene into the child’’s stem cells.s stem cells.

66--Fetal hemoglobinFetal hemoglobin Researchers are studying ways to enhance Researchers are studying ways to enhance

production of fetal hemoglobin in people with production of fetal hemoglobin in people with thalassemia. Fetal hemoglobin is the type of thalassemia. Fetal hemoglobin is the type of hemoglobin made by the body before birth. After hemoglobin made by the body before birth. After birth, the body usually switches from making fetal birth, the body usually switches from making fetal hemoglobin to the adult form of hemoglobin. Some hemoglobin to the adult form of hemoglobin. Some children have a gene variant that prevents the children have a gene variant that prevents the switch, and their continuing production of fetal switch, and their continuing production of fetal hemoglobin lessens the severity of their illness. hemoglobin lessens the severity of their illness. Researchers are testing ways to enhance fetal Researchers are testing ways to enhance fetal hemoglobin production after birth.hemoglobin production after birth.

How Can Thalassemia Be Prevented?How Can Thalassemia Be Prevented?

Although thalassemia cannot be prevented, Although thalassemia cannot be prevented, it can be identified before birth by prenatal it can be identified before birth by prenatal diagnosis. diagnosis.

People who have or believe that they may People who have or believe that they may carry the thalassemia genes can receive carry the thalassemia genes can receive genetic counseling to avoid passing the genetic counseling to avoid passing the disorder to their children.disorder to their children.

Living With ThalassemiaLiving With Thalassemia

1.1. The CooleyThe Cooley’’s Anemia Foundation offers s Anemia Foundation offers support to people with various types of support to people with various types of thalassemia through its Thalassemia Action thalassemia through its Thalassemia Action Group. Group.

2.2. If you have moderate or severe thalassemia, If you have moderate or severe thalassemia, you need to take care of your overall health. you need to take care of your overall health.

Follow your treatment plan. See your doctor regularly Follow your treatment plan. See your doctor regularly for checkups and treatment. for checkups and treatment.

If you must have regular blood transfusions and iron If you must have regular blood transfusions and iron chelation therapy, it is important to continue with chelation therapy, it is important to continue with treatment as recommended. treatment as recommended.

If you have regular blood transfusions, you should If you have regular blood transfusions, you should avoid taking vitamins or other supplements containing avoid taking vitamins or other supplements containing iron. iron.

Maintain a healthy diet. Your doctor may also give you Maintain a healthy diet. Your doctor may also give you a supplement of folic acid (a B vitamin) every day to a supplement of folic acid (a B vitamin) every day to help your body make new red blood cells. help your body make new red blood cells.

Get a flu shot every year and the pneumococcal vaccine Get a flu shot every year and the pneumococcal vaccine to prevent infectto prevent infect

Key PointsKey Points Thalassemia is an inherited blood disorder that Thalassemia is an inherited blood disorder that

can cause mild to severe anemia. can cause mild to severe anemia. Thalassemia involves problems with the Thalassemia involves problems with the

production of hemoglobin in red blood cells. production of hemoglobin in red blood cells. As a result, a person with thalassemia doesnAs a result, a person with thalassemia doesn ’’t t have enough hemoglobin or red blood cells to have enough hemoglobin or red blood cells to carry oxygen throughout the body (anemia). carry oxygen throughout the body (anemia).

Two main types of thalassemia are alpha and Two main types of thalassemia are alpha and beta thalassemia. Alpha thalassemia occurs beta thalassemia. Alpha thalassemia occurs when there is a problem with the alpha globin when there is a problem with the alpha globin chain that is part of hemoglobin. Beta chain that is part of hemoglobin. Beta thalassemia occurs when there is a problem with thalassemia occurs when there is a problem with the beta globin chain. the beta globin chain.

Mild, moderate, and severe forms of Mild, moderate, and severe forms of thalassemia occur. Severe beta thalassemia is thalassemia occur. Severe beta thalassemia is often called Cooleyoften called Cooley’’s anemia. s anemia.

The most common severe form of thalassemia The most common severe form of thalassemia seen in the United States is beta thalassemia seen in the United States is beta thalassemia major, or Cooleymajor, or Cooley’’s anemia. It mainly affects s anemia. It mainly affects people from Mediterranean countries and Asia. people from Mediterranean countries and Asia.

Some people are Some people are ““silent carrierssilent carriers”” with no with no symptoms. Other carriers have mild anemia but symptoms. Other carriers have mild anemia but usually need no treatment. Carriers can pass usually need no treatment. Carriers can pass thalassemia genes on to their children. thalassemia genes on to their children.

Severe thalassemia is treated with frequent Severe thalassemia is treated with frequent blood transfusions and iron chelation blood transfusions and iron chelation therapy to remove excess iron that builds up therapy to remove excess iron that builds up in the body from the transfusions. in the body from the transfusions.

Bone marrow or stem cell transplants have Bone marrow or stem cell transplants have cured thalassemia in some children, but this cured thalassemia in some children, but this treatment is not available for most people treatment is not available for most people with thalassemia. with thalassemia.

Researchers are studying new treatments, Researchers are studying new treatments, including ways to cure thalassemia through including ways to cure thalassemia through stem cell and gene therapies. stem cell and gene therapies.

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