Alpha-thalassemia

The severity of the symptoms of alpha-thalassemia varies from person to person. Symptoms usually start within the first year of life. Over time symptoms such as fatigue, anemia, poor growth, poor weight gain and bone changes, such as enlargement of the upper jaw, around the eyes and forehead, may worsen and indicate the need for a blood transfusion. The ages at which these symptoms worsen, if at all, depends on the severity of disease in each individual.

Alpha-thalassemia is caused by deletions or mutations in the HBA1 and/or HBA2 genes, meaning pieces of the gene are missing or changed. Both of these genes tell the body to make a protein called alpha globin, which is a component of hemoglobin. Hemoglobin is the protein in red blood cells responsible for carrying and delivering oxygen to cells throughout the body. We each have two copies, called alleles, of HBA1 and HBA2, for a total of four alleles. When one or more of these alleles has a change, the body cannot produce alpha globin correctly, resulting in a reduced ability of red blood cells to carry oxygen throughout the body. If three or four alleles are changed, the cells produce an abnormal form of hemoglobin called hemoglobin H or hemoglobin Bart, respectively. These types of hemoglobin do not easily release oxygen, preventing cells from receiving the oxygen they need. Hemoglobin H can form abnormal clumps in the cells that can lead to cell death. Because the cells do not receive the oxygen they need, affected individuals experience symptoms from mild to severe, such as anemia, enlarged liver and spleen, yellowing of the eyes and skin, overgrowth of the upper jaw, prominent forehead, and death.

If a child is diagnosed with alpha-thalassemia, the parents can have testing to determine if they are also affected with a mild form of thalassemia. The parents can be offered genetic testing after the affected family member has genetic testing and the exact types of changes their HBA1 and/or HBA2 genes have been determined. Parental testing allows for an accurate assessment of the risk of alpha-thalassemia in siblings or future children. The siblings of an affected child should be tested to determine if they also have the disease. First degree relatives of an affected individual (parents, siblings) should have testing for thalassemia, for their own health and to learn their risks for having an affected child.

Genetics professional, such as a geneticist or genetic counselor, can coordinate testing, interpret results, and provide information about treatment and risk to other family members. Genetic counselors can refer their patients with alpha-thalassemia to the appropriate specialists and for appropriate testing. Hematologists specialize in blood disorders and can watch for blood and organ health. Other specialists may be necessary if complications arise, such as in internal medicine specialist if problems with the spleen, liver or gallbladder occur. A maternal fetal medicine specialist should be consulted for women who are pregnant with an affected fetus and also for affected women who are pregnant due to potential complications. A dietician can help you maintain a healthy diet that provides you with the appropriate nutrients and avoids iron overload, which can occur in people with alpha-thalassemia.

Patients with alpha-thalassemia must be conscious of the foods they eat and the nutrients they consume. People who do not receive blood transfusions are advised to avoid a high iron diet, drink tea with meals which decreases the amount of iron absorbed from food, and take a folate supplement.
Patients who receive transfusions are at risk of iron overload. Iron can accumulate in the heart and other organs, causing damage. These individuals are advised to consume a low iron diet. However, if iron load is well controlled by medication, this may not be as crucial. A dietician can provide tailored guidance as to the amount of iron that should be consumed per day. These individuals may still be anemic and crave foods such as beef. However, cereals and breads are a better choice to receive dietary iron. Foods such as tea, dairy and coffee can decrease the amount of iron absorbed. Juice enhances iron absorption.
Maintaining calcium levels is crucial for strong bones. The best sources of calcium are dairy products such as milk, cheese and yogurt. Alternative sources include calcium fortified orange juice, Tums antacid, broccoli and kale. Iron overload can lead to iron depositing in and damaging organs that are necessary to maintain strong bones. A dietician can provide guidance for adequate calcium intake.
Patients with alpha-thalassemia should avoid alcohol and tobacco.

Alpha-thalassemia does not have an abbreviation. However, the two types of alpha-thalassemia that can cause symptoms, hemoglobin Bart syndrome and hemoglobin H disease are abbreviated Hb Bart syndrome and HbH disease.

Alpha-thalassemia is a fairly common blood disorder that results in reduced amounts of hemoglobin, the protein in red blood cells that carries oxygen to cells in the body. This lowers the amount of oxygen that cells receive, causing various health problems, including anemia.

There are two types of alpha-thalassemia that can cause serious health problems and two types that can cause mild symptoms. The most serious is called hemoglobin Bart. Fetuses (unborn babies) affected with hemoglobin Bart usually do not survive beyond the newborn period. While still in the uterus (womb), they experience health complications, including swelling, fluid buildup around the organs, heart defects and genital abnormalities. The mothers of these fetuses experience health complications including preeclampsia, (extreme high blood pressure), excessive amniotic fluid or reduced amniotic fluid, bleeding in the genital tract, and premature delivery. Due to the lack of effective treatment and severe complications, termination of these pregnancies is sometimes considered. The less severe form of alpha-thalassemia is called hemoglobin H. Symptoms associated with this form include enlarged spleen, anemia, yellowing of the eyes and skin, and bone overgrowth. Symptoms vary from mild to severe. These individuals typically live into adulthood.

Alpha-thalassemia is caused by deletions or mutations in the HBA1and/or HBA2 genes, meaning pieces of the gene are missing or changed. Both of these genes tell the body to make a protein called alpha globin, which is a component of hemoglobin. Hemoglobin is the protein in red blood cells responsible for carrying and delivering oxygen to cells throughout the body. We each have two copies, called alleles, of HBA1 and HBA2, for a total of four alpha globin alleles. When one or more of these alleles has a change, the body cannot produce alpha globin correctly, resulting in a reduced ability of red blood cells to carry oxygen throughout the body. If three or four alleles are changed, the cells produce an abnormal form of hemoglobin called hemoglobin H or hemoglobin Bart, respectively. These types of hemoglobin do not easily release oxygen to the cells. Therefore, cells can not get the oxygen they need. Hemoglobin H can also form abnormal clumps in the cells that can lead to cell death. People with two alleles changed have hemoglobin trait and may have anemia. People with only one allele changed are called silent carriers.

Because two genes are involved, the inheritance of alpha-thalassemia is complex, but usually follows an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means that people who have one changed allele do not have disease (and are called carriers) while, those with two changed alleles have disease. Alpha-thalassemia is more complicated because there are two genes involved. An individual can inherit between 0 and 4 changed copies of genes HBA1 and/or HBA2. In general, people with more changed copies have more health complications as compared to individuals with fewer changed gene copies.

Alpha-thalassemia can be diagnosed by blood analysis. Genetic testing can also be performed to determine the exact changes to the genes involved, HBA1 and HBA2. Blood testing involves analysis of the size, shape, color and number of red blood cells. The hemoglobin is also analyzed to determine how much and which types of hemoglobin are present. Genetic testing can determine the specific changes of the genes involved, HBA1 and HBA2. Understanding the exact changes involved with these genes will enable more accurate prediction of the severity of the disease and also allow the health care provider to provide an accurate risk of future pregnancies being affected. Genetic testing is necessary if parents are concerned their pregnancy is affected and want to test their fetus before delivery.

Treatment for alpha-thalassemia depends on the specific type an individual has. Fetuses with hemoglobin Bart typically do not survive beyond the newborn period. They usually have serious symptoms including birth defects of the heart, limbs and genitals, and delays in development. The mothers of these infants often experience maternal complications including severe anemia, preeclampsia, an abnormal amount of amniotic fluid, and delivery complications. Individuals with hemoglobin H disease benefit from folic acid supplements, and a non-iron containing multivitamin may be recommended. Patients should avoid oxidative compounds and medications, and a high iron diet. Any infections should be treated promptly. There should be ongoing monitoring of growth, bone health, spleen size, inflammation of the gallbladder, leg ulcers and fatigue. Blood transfusions, or removal of the spleen or gallbladder may be indicated. During pregnancy, women with Hemoglobin H disease should be monitored for potential serious complications. People who are carriers of alpha-thalassemia may have mild anemia, which would need monitoring and potentially treatment.

The symptoms of alpha-thalassemia are variable, according to the severity of disease. Alpha-thalassemia is caused by mutations in the HBA1 and/or HBA2 genes. We each have two copies of HBA1 and HBA2, for a total of four copies.

Those who have no working copies of HBA1 or HBA2 have the most severe form, hemoglobin Bart syndrome. Symptoms begin prenatally and death usually occurs in newborns. Doctors should be aware that these pregnancies can be complicated by preeclampia (extreme hypertension), excessive amniotic fluid or reduced amniotic fluid, bleeding in the genital tract, and premature delivery. During pregnancy women with alpha-thalassemia may experience more severe anemia. In the third trimester, increased rate of premature labor, preeclampsia and congestive heart failure have been reported.

The less severe form of alpha-thalassemia is called hemoglobin H disease. These individuals have one working copy of HBA1 or HBA2. Symptoms of this form vary from mild to more severe. Symptoms usually start by age one, but for some symptoms do not begin until adulthood. Doctors should watch for anemia, enlarged spleen, gallstones, slowed growth and decreased bone density. With time, patients may benefit from a blood transfusion. Indications that a blood transfusion may increase quality of life include fatigue, anemia, poor growth, poor weight gain and bone changes, such as enlargement of the upper jaw, around the eyes and forehead.

Those with alpha-thalassemia trait have two working copies of HBA1 or HBA2. They should be watched for mild anemia.

Alpha-thalassemia is caused by deletions or mutations in the HBA1 and/or HBA2 genes, meaning pieces of the gene are missing or changed. Both of these genes tell the body to make a protein called alpha globin, which is a component of hemoglobin. Hemoglobin is the protein in red blood cells responsible for carrying and delivering oxygen to cells throughout the body.

Genetics is a growing field, and scientists and doctors do not know everything there is to know about all conditions, including all possible changes in the genes that cause diseases. Therefore, sometimes when individuals have genetic testing the results can fall into a category called ‘variants’ or ‘variants of uncertain significant’. For HBA1 and HBA2, the genes associated with alpha-thalassemia, almost 100% of these changes are known. However, a ‘variant’ result is still possible.

Our genes, such as HBA1 and HBA2, are stretches of DNA. Our DNA is composed of ‘letters’, four small molecules abbreviated A, T, C, and G. With genetic testing, the HBA1 and HBA2 genes are searched to see if stretches of the ‘letters’ are missing. This is the most common type of change in these genes. The genes are also sequenced, meaning each ‘letter’ of the gene is read to look for ‘misspellings’. Sometimes these changes do not affect how the gene functions and do not cause disease. Sometimes we know that a particular change does cause disease. Other times there is a new or rare change, and scientists have not yet figured out if that particular change causes disease, causes a mild form of the disease, or does not cause disease. Therefore, some changes have ‘uncertain significance’.

As more genetic testing is performed on patients, more information will become available for those with ‘variant’ results. A geneticist or genetic counselor may recommend a return visit in the future to review new information and what it might mean for you. Genetic counselors can be found on the National Society of Genetic Counselors website.

The symptoms of alpha-thalassemia are variable, according to the severity of disease. Alpha-thalassemia is caused by mutations in the HBA1 and/or HBA2 genes. We each have two copies of HBA1 and HBA2, for a total of four copies.

Babies with no working copies of the HBA1 or HBA2 genes have the most severe form, hemoglobin Bart syndrome. Symptoms begin prenatally and include swelling of the body, fluid surrounding the brain, heart and lungs, severe anemia, enlarged liver and spleen, heart defects and defects of the urinary and genital system. Death usually occurs in newborns. These pregnancies can be complicated by preeclampia (extreme hypertension), excessive amniotic fluid or reduced amniotic fluid, bleeding in the genital tract, and premature delivery.

The less severe form of alpha-thalassemia is called hemoglobin H disease. These individuals have one working copy of the HBA1 or HBA2 gene. Symptoms of this form vary from mild to more severe. Symptoms usually start by age one, but for some, symptoms do not begin until adulthood. Those with more severe symptoms can have anemia, enlarged spleen, gallstones, slowed growth and decreased bone density. 24% to 80% of these patients receive blood transfusions, and blood transfusions start between 0 and 3 years of age. Those with less severe symptoms are less like to receive blood transfusions, with 3% to 29% chance. The age at first blood transfusion is older, between 6 and 15 years of age. The anemia, enlarged spleen, gallstones, slowed growth and decreased bone density are more mild. People with hemoglobin H disease may experience bone changes of the face, such as enlargement of the upper jaw, protruding of the forehead and enlargement of the cheekbones. In very severe cases, infants have died prenatally or soon after birth. The cause of this extreme variability is unknown.

People with alpha-thalassemia trait have two working copies of HBA1 or HBA2 genes. They have mild anemia. Silent carriers have three working copies or HBA1 or HBA2 genes and do not experience symptoms.

During pregnancy, women with hemoglobin H may experience more severe anemia. In the third trimester, increased rate of premature labor, preeclampsia and congestive heart failure have been reported.

The transition from childhood to adulthood is difficult for anyone. However, teens who also have a disease to manage can have a particularly difficult transition. Teens can understand the medical aspect of their disease. However, they may have a sense of invincibility from danger and may not be as compliant to treatment as they once were. There are a few things parents can do to help. This includes gradually handing over responsibilities to teens, including relationships and interactions with health care providers and negotiating these responsibilities with teens. Seek help and guidance from parents who have gone through this adjustment, and talk to your doctor about professional help if needed. Helpful information can be found online from the Northern California Comprehensive Thalassemia Center (living with thal transition
The Thalassemia Action Group is a national peer support network of patients that provide information on thalassemia. Teens can join to receive support. Contact info: (800) 935-0024 or (800) 522-7222 (e-mail: ncaf@aol.com). You and your teen could also subscribe to a listserv (thalassemia@listbot.com) or join an online support group.

Treatment of your child will depend on the severity of symptoms. Patients with mild symptoms will visit the doctor about twice per year, but this will vary depending on symptoms and your doctor’s recommendations. Symptoms usually start by age one, but for some, symptoms do not begin until adulthood. At doctor visits, several factors will be monitored. These include growth, development, possible facial bone deformities, dental status, enlarged liver and spleen, and hemoglobin levels. Bone density and liver iron should be monitored beginning in early adolescence.

Some parents try making physician visits happy events by discussing it with their child, bringing special toys to appointments or planning a special outing for after the appointment. With age, children better understand why they are going to the doctor.

Suggestions can be found on the Thalassemia Patients and Friend support group forum: http://www.thalassemiapatientsandfriends.com/index.php/topic,4470.0.html

Alpha-thalassemia is not a condition that is on the Recommended Uniform Screening Panel, a list of recommended diseases to for the newborn screening panel. However, some states do screen for alpha-thalassemia. Also, there are similar conditions that are on the Uniform Screening Panel, and if one of those conditions is detected, doctors may consider the possibility of alpha-thalassemia. The list can be found at this link: HRSA Recommended newborn screening panel
Because of the complexity of the inheritance of alpha-thalassemia, testing and interpretation of test results is best performed by genetic professionals, including genetic counselors. If you would like to speak with a genetic counselor, a genetic counselor can be found on the National Society of Genetic Counselors website.

As of June 2019, there are many studies, completed and ongoing, for blood disorders, including alpha-thalassemia. Please consult Clinicaltrials.gov for a list of the current studies in the United States.

Alpha-thalassemia can be diagnosed by blood analysis. Genetic testing can also be performed to determine the exact changes to the genes involved, HBA1 and HBA2.

Blood testing involves analysis of the size, shape, color and number of red blood cells and is called a complete blood count, or CBC. The hemoglobin is also analyzed to determine how much and which types of hemoglobin are present. The best test for detecting the abnormal hemoglobin of alpha-thalassemia is called hemoglobin electrophoresis. High performance liquid chromotography (HPLC) may also be used to look at a person’s hemoglobin properties.

An analysis of red blood cells will show that all those affected will have blood cells that are unusually shaped, lighter in color, and an increased number of immature blood cells.
Babies with the most severe form, hemoglobin Bart, will have enlarged red blood cells and an increased amount of hemoglobin in cells. Those with less severe alpha-thalassemia have decreased red blood cell size, a decreased amount of hemoglobin in each red blood cell, and inclusion bodies, which are clumps of abnormal hemoglobin, in the red blood cells.

An analysis of hemoglobin will reveal the presence of abnormal hemoglobin, including hemoglobin Bart in babies with hemoglobin Bart syndrome, and hemoglobin H in those with hemoglobin H disease. The presence of a normal level of a type of hemoglobin called hemoglobin A2 would rule out a similar condition, beta-thalassemia, which normally has an increased level of hemoglobin A2. Iron deficiency also must be ruled out since iron deficiency can mimic alpha-thalassemia.

Genetic testing can determine the specific changes of the genes involved, HBA1 and HBA2. Understanding the exact changes involved with these genes can aid in the prediction of the severity of the disease and management of symptoms. DNA testing also allows the health care provider to provide an accurate risk of future pregnancies being affected. Genetic testing is necessary if parents are concerned their pregnancy is affected and want to have prenatal genetic testing. Those who are carriers of alpha-thalassemia may not have symptoms or abnormal blood testing and can only be detectable by genetic testing.

90% of changes to the HBA1 and HBA2 genes are deletions of pieces of the gene. 10% are small changes to just one ‘letter’ of the gene. It is important to keep in mind that a patient can have more than one type of hemoglobin disease and having a diagnosis of alpha-thalassemia does not rule out having other hemoglobin diseases.

Diagnosis can be made during a pregnancy with procedures called chorionic villus sampling (CVS) and/or amniocentesis. Because of the complexity of the inheritance of alpha-thalassemia, testing and interpretation of test results is best performed by genetic professionals, including genetic counselors. Genetic counselors can be found on the National Society of Genetic Counselors website.

Treatment for alpha-thalassemia depends on the specific type an individual has. Hemoglobin Bart is the most severe. Hemoglobin H can range from mild to severe. Carriers may experience mild anemia or no symptoms at all.
Fetuses with hemoglobin Bart typically do not survive beyond the newborn period. A few babies have received transfusions while in the uterus or immediately after delivery and have survived to five years of age. These fetuses are monitored before birth by ultrasonography and, as children, require regular transfusions. They usually have serious symptoms including birth defects of the heart, limbs and genitals, and delays in development. The mothers of these infants often experience maternal complications including severe anemia, preeclampsia, an abnormal amount of amniotic fluid, and delivery complications. Because of these serious complications, prenatal diagnosis and termination of affected pregnancies can be considered.

For individuals with hemoglobin H disease, supplementation of folic acid is generally recommended, especially in children, pregnant women, and women who may become pregnant. Because affected individuals can have low levels of certain vitamins, a non-iron containing multivitamin is usually recommended. Patients should avoid oxidative compounds and medications, and a high iron diet. Any infections should be treated promptly. There should be ongoing monitoring of growth, bone health, spleen size, leg ulcers, fatigue, and inflammation of the gallbladder.

During pregnancy, women with Hemoglobin H disease should be monitored for potential preeclampsia, congestive heart failure, threatened miscarriage and worsening anemia. Children should be monitored for growth and development every 6-12 months.
Usually blood transfusions are not necessary for individuals with hemoglobin H disease. However, over time symptoms such as poor cardiac function, fatigue, anemia, poor growth, poor weight gain and bone changes, such as enlargement of the upper jaw, around the eyes and forehead, may worsen and indicate the need for a blood transfusion. The ages at which these symptoms worsen, if at all, depends on the severity of disease in each individual.

People affected with alpha-thalassemia experience anemia. Patients should be watched for anemia especially if they have an infection, a fever, an enlarged spleen, or are pregnant. Patients can experience a hemolytic crisis, which is a rapid destruction of red blood cells. During a hemolytic crisis, patients require immediate medical treatment, possibly including a blood transfusion. During a hemolytic crisis and transfusion, hydration and fever control is very important. The cause of infection should be identified and treated. Patients who receive blood transfusions, and even those who do not, may develop iron overload, as determined by measurements of liver iron. These patients may require chelation therapy, treatments to rid the body of excess iron. Patients should be monitored for iron overload and hemoglobin levels at least annually.

For those with an enlarged spleen, having the spleen removed may improve symptoms. Risks associated with this include blood infection and blood clots. Aspirin is recommended for those who undergo this surgery to control clotting. For those with persistent gallstones that do not respond to antibiotics or surgical removal of the stones, removal of the gallbladder may be indicated.

Carriers of alpha-thalassemia may have mild anemia, which would need monitoring and potentially treatment.

During pregnancy women with alpha-thalassemia may experience more severe anemia. In the third trimester, increased rates of premature labor, preeclampsia and congestive heart failure have been reported.

Those with alpha-thalassemia will show symptoms. However, the severity of the symptoms will vary from person to person and according to the specific form of the disease. Mutations in the HBA1 and HBA2 genes lead to changes in the hemoglobin protein; however, it is the quantity of the altered genes (mutations) that determine the presence and severity of symptoms of alpha-thalassemia.

Treatment for alpha-thalassemia depends on the specific type an individual has. Hemoglobin Bart is the most severe. Hemoglobin H can range from mild to severe. Carriers may experience mild anemia or no symptoms at all.
Genetics professional, such as a geneticist or genetic counselor, can coordinate testing, interpret results, and provide information about treatment and risk to other family members. Genetic counselors can refer their patients with alpha-thalassemia to the appropriate specialists and for appropriate testing.
Fetuses with hemoglobin Bart typically do not survive beyond the newborn period. A few have received transfusions while in the uterus or immediately after delivery and have survived to five years of age. These fetuses are monitored by ultrasonography and as children require regular transfusions. They usually have serious symptoms including birth defects of the heart, limbs and genitals, and delays in development. The mothers of these infants often experience maternal complications including severe anemia, preeclampsia, an abnormal amount of amniotic fluid, and a difficult delivery. Because of these serious complications, prenatal diagnosis and termination of affected pregnancies may be considered. A genetic counselor can help with this decision. A maternal fetal medicine specialist should follow these pregnancies to manage complications.
For those with hemoglobin H disease, supplementation of folic acid is generally recommended, especially in kids, pregnant women, and women who may become pregnant. Because affected individuals can become low on certain vitamins, a non-iron containing multivitamin is usually recommended. Patients should avoid oxidative compounds and medications, and a high iron diet. Any infections should be treated promptly. There should be ongoing monitoring of growth, bone health, spleen size, inflammation of the gallbladder, leg ulcers and fatigue. Internal medicine specialists should be consulted for any organ damage. A physician can help ensure patients do not take medications they should avoid. A dietician can help with avoiding iron overload and getting proper nutrients.
During pregnancy, women with Hemoglobin H disease should be monitored for potential preeclampsia, congestive heart failure, threatened miscarriage and worsening anemia. These women should consult with a maternal fetal medicine specialist for potential complications. Children should be monitored for growth and development every 6-12 months.

Usually blood transfusions are not necessary. However, over time symptoms such as poor cardiac function, fatigue, anemia, poor growth, poor weight gain and bone changes, such as enlargement of the upper jaw, around the eyes and forehead, may worsen and indicate the need for a blood transfusion. The ages at which these symptoms worsen, if at all, depends on the severity of disease in each individual.

Those affected with alpha-thalassemia experience anemia. Patients should be watched for anemia particularly closely if they have an infection, a fever, an enlarged spleen, or are pregnant. Patients can experience a hemolytic crisis, which is a rapid destruction of red blood cells. During a hemolytic crisis, patients require immediate medical treatment, possibly including a blood transfusion. During a hemolytic crisis and transfusion it is important patients receive adequate hydration and fever is controlled. The cause of infection should be identified and treated. Patients who receive blood transfusions, and even those who do not, may develop iron overload, as determined by measurements of liver iron. These patients may require chelation therapy, treatments to rid the body of excess iron. Patients should be monitored for iron overload and hemoglobin levels at least annually. A hematologist should be consulted to manage blood health.
For those with an enlarged spleen, having a splenectomy may improve symptoms. Risks associated with this include blood infection and blood clots. Aspirin is recommended for those who undergo this surgery to control clotting. For those with persistent gallstones that do not respond to antibiotics or surgical removal of the stones, removal of the gallbladder may be indicated. An internal medicine specialist should be consulted for organ damage.

People who are carriers of alpha-thalassemia may have mild anemia, which would need monitoring and potentially treatment.

Carriers of alpha-thalassemia will not typically have serious complications associated with the disease. However, there is the risk of having children affected with the disease. Carriers have changes in one or two of their HBA1 and/or HBA2 genes, the genes associated with the disease. Individuals with changes in three or four of these genes will typically have serious symptoms. If two carriers of alpha-thalassemia have a child, that child is at risk of inheriting the changed copies of the genes from both parents and having a serious form of the disease. It is important for couples to understand their risk before having children so they can make the decision best for them. Some couples decide they will still have children and want to know the risk so they will know what to expect. Some couples will choose to adopt instead of having biological children. Other couples will choose to have in vitro fertilization (IVF) and pre-implantation genetic diagnosis (PGD), where embryos are grown in a lab and only those not affected with the disease are implanted in the mother’s uterus.

Alpha-thalassemia and low iron can look alike. Most types of alpha-thalassemia cause the red blood cells to be smaller than usual, called microcytosis. Iron deficiency can also cause microcytosis, and is more common than alpha-thalassemia. Therefore, alpha-thalassemia is sometimes misdiagnosed as low iron and patients are prescribed iron supplementation. However, in alpha-thalassemia patients, this can cause iron overload and damage to organs. Consult with your doctor before taking iron. A consultation with a dietician can provide you with a tailored discussion of what foods and supplements you should consume and which to avoid.

The decision to have transfusions depends on signs that the body can no longer tolerate low levels of hemoglobin. These symptoms include heart exams showing increased cardiac effort, fast heart rate, sweating, poor eating and poor growth. Less commonly, the shape of the bones of the face can change or the spleen is enlarged. Deciding to have regular transfusions is a decision to be made between doctor and patient and is based on symptoms, hemoglobin levels and quality of life with and without regular transfusions. Patients can try having regular transfusions on a trial basis to help decide if that is the right decision for them.

You can find out the risk of having a baby with alpha-thalassemia before becoming pregnant. If you have not already been tested for alpha-thalassemia, you can meet with a genetic counselor who can arrange that testing. Your family physician may also order testing. Knowing as much detail about your family member’s alpha-thalassemia will help with the test interpretation. Genetic counselors can be found on the National Society of Genetic Counselors website.
Your current or future partner can also have testing to determine the risk to future pregnancies. If you find that there is a risk, there are a few different options for you. Some couples decide they will still have children and want to know the risk so they will know what to expect. Some couples will choose to adopt instead of having biological children. Other couples may choose to have in vitro fertilization (IVF) and pre-implantation genetic diagnosis (PGD), where embryos are grown in a lab and only those unaffected with the disease are implanted in the mother’s womb.

Patients with hemoglobin H disease frequently have an enlarged spleen. Fewer individuals with hemoglobin H disease are choosing to have their spleen removed because of potential blood clotting complications. Having the spleen removed is considered if the patient has an increased need for blood transfusions and medication can no longer regulate iron levels. Having an enlarged spleen does not necessarily mean it must be removed, but it should be monitored.

School age kids with alpha-thalassemia begin to realize that they are different from their peers because they may need to go to the doctor more often and take medications their friends do not have to. To help children adapt to their emerging self-awareness, they can start making more choices about their own medical treatment, such as where an IV is placed. Children can be encouraged to start asking their doctor questions they may have about their disease.

Allowing opportunities for your child to socialize with other kids with alpha-thalassemia or other similar medical conditions helps them feel like they are not alone but are a part of a community. The Painted Turtle is a summer camp in California for kids with serious medical conditions, including thalassemia. [link url=" http://thepaintedturtle.org” target=”_blank”>The Painted Turtle

Contacting The Painted Turtle may provide information about other camps or groups available to you in your area.

A genetics professional, such as a genetic counselor, can help you understand what your results mean and determine if further testing would be helpful to you. Genetic counselors can be found on the National Society of Genetic Counselors website.

If a person has alpha-thalassemia, that means there is a change to that individual’s DNA, and that change will be present in every cell throughout the body. Once a person has been given an accurate diagnosis of alpha-thalassemia, this will not change throughout the person’s life. Likewise, a person cannot develop alpha-thalassemia later in life. Therefore, it is not necessary to have testing with every pregnancy, unless your health care provider determines the original results need clarification.

However, if you are concerned for thalassemia in your baby, each new pregnancy has a risk. If you and your partner are each alpha thalassemia carriers, then each pregnancy has a risk for the baby having a more severe form of the disease. You can discuss prenatal testing with your obstetrician or a maternal fetal medicine specialist.

Alpha-thalassemia is caused by changes in the HBA1 and/or HBA2 genes. We each have two copies of HBA1 and HBA2, for a total of four copies. Up to 5% of the world’s population has a change in at least one copy of these genes. However, these individuals typically have ancestors from Southeast Asia or the Mediterranean regions of the world.

Alpha-thalassemia is caused by deletions or mutations in the HBA1 and/or HBA2 genes, meaning pieces of the gene are missing or changed. Both of these genes tell the body to make a protein called alpha globin, which is a component of hemoglobin. Hemoglobin is the protein in red blood cells responsible for carrying and delivering oxygen to cells throughout the body. We each have two copies, called alleles, of HBA1 and HBA2, for a total of four alleles. One copy of HBA1 and one copy of HBA2 come from mom in the egg cell. The other copies of HBA1 and HBA2 come from dad through the sperm cell.

Because two genes are involved, the inheritance of alpha-thalassemia is complex, but usually follows an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means that those who have one changed allele do not have disease, and those with two changed alleles have disease. Therefore, individuals can have changes to one gene and have no symptoms. If two of these individuals (carriers) have a child together who inherited changed genes from each parent, the child will have the disease. In this way, the disease can appear in a family despite no one else in the extended family having that same disease. Inheritance is more complicated with alpha-thalassemia because there are two genes involved. An individual can inherit between 0 and 4 changed copies of HBA1 and/or HBA2. Typically, those with more changed copies have more health complications as compared to people with fewer copies of the changed genes.

When one or more of these alleles has a change, the body cannot produce alpha globin correctly, resulting in a reduced ability of red blood cells to carry oxygen throughout the body. If three or four alleles are changed, the cells produce an abnormal form of hemoglobin called hemoglobin H or hemoglobin Bart, respectively. These types of hemoglobin do not easily release oxygen. Therefore, they cannot transport oxygen to the cells. People with two alleles changed have hemoglobin trait and might have anemia. People with only one allele changed are called silent carriers.

Because of the complexity of the inheritance of alpha-thalassemia, genetic testing and interpretation of test results is best performed by genetic professionals, including genetic counselors. Genetic counselors can be found on the National Society of Genetic Counselors website.

Northern California Comprehensive Thalassemia center is a thalassemia treatment center that provides care and research for patients with thalassemia. Donations can be made at: thalassemia how to help

The Vancouver Thalassemia Society of BC provides funds for patients with thalassemia. http://bcthalassemia.org/showcontent.aspx?MenuID=1848

Alpha-thalassemia can be diagnosed by blood analysis. Genetic testing can also be performed to determine the exact changes to the genes involved, HBA1 and HBA2.

Blood testing involves analysis of the size, shape, color and number of red blood cells and is called a complete blood count, or CBC. The hemoglobin is also analyzed to determine how much and which types of hemoglobin are present. The best test for detecting the abnormal hemoglobin of alpha-thalassemia is called high performance liquid chromatography (HPLC) or electrophoresis.

An analysis of red blood cells will show that affected individuals will have blood cells that are unusually shaped, lighter in color, and an increased number of immature blood cells.
People with the most severe form, hemoglobin Bart, will have enlarged red blood cells and an increased amount of hemoglobin in cells. Those with less severe alpha-thalassemia have decreased red blood cell size, a decreased amount of hemoglobin in each red blood cell, and inclusion bodies, which are clumps of abnormal hemoglobin, in the red blood cells.

An analysis of hemoglobin will reveal the presence of abnormal hemoglobin, including hemoglobin Bart in those with hemoglobin Bart syndrome, and hemoglobin H in those with hemoglobin H disease. The presence of a normal level of a type of hemoglobin called hemoglobin A2 would rule out a similar condition, beta-thalassemia, which normally has an increased level of hemoglobin A2. Iron deficiency also must be ruled out since iron deficiency can mimic alpha-thalassemia.

Genetic testing can determine the specific changes of the genes involved, HBA1 and HBA2. Understanding the exact changes involved with these genes will enable more accurate prediction of the severity of the disease and better manage symptoms. DNA testing also allows the health care provider to provide an accurate risk of future pregnancies being affected. Genetic testing is necessary if parents are concerned about a pregnancy being affected and want to have prenatal genetic testing. People who are carriers of alpha-thalassemia may not have symptoms or abnormal blood testing and can only be detectable by genetic testing.

90% of changes to the HBA1 and HBA2 genes are deletions of pieces of the gene. 10% are small changes to just one ‘letter’ of the gene. It is important to keep in mind that a patient can have more than one type of hemoglobin disease and having a diagnosis of alpha-thalassemia does not rule out having other hemoglobin diseases.

Diagnosis can be made early in a pregnancy with a procedure called chorionic villus sampling (CVS). Because of the complexity of the inheritance of alpha-thalassemia, testing and interpretation of test results is best performed by genetic professionals, including genetic counselors. Genetic counselors can be found on the National Society of Genetic Counselors website.

To find information about clinical research on alpha-thalassemia, look at clinicaltrials.gov. Once on the website, you can search for studies involving alpha-thalassemia. Keeping in contact with support groups can help you stay informed about the latest clinical trials and drugs. Following forums and reading what others have posted can alert you to any new trials or drugs. The Thalassemia International Federation also has information on current research and treatment.

The US Center of Disease Control has listed several treatment centers for thalassemia through the country: CDC thalassemia centers

Alpha-thalassemia is a rather common disease. It is possible there are local support groups. Genetic counselors and other health care providers would be able to provide you with information about local groups. There are also online support groups through which those affected and their families can meet. If there are no regularly held support groups in your area, state or national support groups may have events you can attend and meet others.

Both males and females are equally likely to inherit alpha-thalassemia and pass it on to children. Symptoms in males and females are similar. However, females can experience pregnancy related symptoms, including preeclampsia, congestive heart failure, threatened miscarriage and worsening anemia.

People with a form of alpha-thalassemia called hemoglobin H (HbH) disease should avoid a diet high in iron, unnecessary iron supplements, infections, fever, oxidant drugs such as sulphonamides and some antimalarial drugs. Your doctor can give you more specific information on medications to avoid. A dietician can help you choose a diet with an appropriate amount of iron.

Alpha-thalassemia mostly affects individuals from Southeast Asia, the Mediterranean area, the Indian subcontinent, the Middle East and Africa. This includes the following populations: Italians, Greeks, Cypriots, Sardinians (Mediterranean region), Southeast Asians (Vietnamese, Laotians, Thais, Singaporeans, Filipinos, Cambodians, Malaysians, Burmese, and Indonesians), Chinese, Indians, Bahrainis, Egyptians, Africans, Middle Easterners (Iranians, Pakistanis, and Saudi Arabians), Transcaucasians (Georgians, Armenians, and Azerbaijanis), Romanians, Bulgarian and Albanians.

The form of alpha-thalassemia which results in hydrops fetalis is largely restricted to individuals from Southeast Asia.

Alpha-thalassemia has four different types. These are hemoglobin Bart syndrome (or hemoglobin Bart hydrops fetalis), hemoglobin H disease, alpha-thalassemia trait and alpha-thalassemia silent carrier. Doctors may refer to specific types by their names.

Treatment for alpha-thalassemia depends on the specific type an individual has. Hemoglobin Bart is the most severe. Hemoglobin H can range from mild to severe. Carriers may experience mild anemia or no symptoms at all.
Fetuses with hemoglobin Bart typically do not survive beyond the newborn period. A few have received transfusions while in the uterus or immediately after delivery and have survived to five years of age. These fetuses are monitored prenatally by ultrasonography and as children require regular transfusions. They usually have serious symptoms including birth defects of the heart, limbs and genitals, and delays in development. The mothers of these infants often experience maternal complications including severe anemia, preeclampsia, an abnormal amount of amniotic fluid, and a difficult delivery. Because of these serious complications, parental diagnosis and termination of affected pregnancies are usually considered.
For those with hemoglobin H disease, supplementation of folic acid is generally recommended, especially in children, pregnant women, and women who may become pregnant. Because affected individuals can develop vitamin deficiencies (having too little of a specific vitamin), a non-iron containing multivitamin is usually recommended. Patients should avoid oxidative compounds and medications, and a high iron diet. Any infections should be treated promptly. There should be ongoing monitoring of growth, bone health, spleen size, leg ulcers, fatigue, and inflammation of the gallbladder.
During pregnancy, women with Hemoglobin H disease should be monitored for potential preeclampsia, congestive heart failure, threatened miscarriage and worsening anemia. Children should be monitored for growth and development every 6-12 months.
Usually blood transfusions are not necessary for individuals with Hemoglobin H disease. However, over time symptoms such as poor cardiac function, fatigue, anemia, poor growth, poor weight gain and bone changes, such as enlargement of the upper jaw, around the eyes and forehead, may worsen and indicate the need for a blood transfusion. The ages at which these symptoms worsen, if at all, depends on the severity of disease in each individual.

Individuals with alpha-thalassemia experience anemia. Patients should be watched for anemia particularly closely if they have an infection, a fever, an enlarged spleen, or are pregnant. Patients can experience a hemolytic crisis, which is a rapid destruction of red blood cells. During a hemolytic crisis, patients require immediate medical treatment, possibly including a blood transfusion. During a hemolytic crisis and transfusion adequate hydration and fever control is important. The cause of infection should be identified and treated. Patients who receive blood transfusions, and even those who do not, may develop iron overload, as determined by measurements of liver iron. These patients may require chelation therapy, treatments to rid the body of excess iron. Patients should be monitored for iron overload and hemoglobin levels at least annually.
For those with an enlarged spleen, having the spleen removed may improve symptoms. Risks associated with this include blood infection and blood clots. Aspirin is recommended for those who undergo this surgery to control clotting. For those with persistent gallstones that do not respond to antibiotics or surgical removal of the stones, removal of the gallbladder may be indicated.

Those who are carriers of alpha-thalassemia may have mild anemia, which would need monitoring and potentially treatment.

This disease has a range of symptoms, from mild to very severe; however, the symptom that all individuals with this condition share is anemia. Anemia typically causes pale skin, weakness, and fatigue. People with the mild form of the disease may be misdiagnosed as having low iron levels but when given iron, their symptoms will not improve, indicating the need for further investigation.

Cooley’s Anemia Foundation
330 Seventh Avenue #900
New York NY 10001
Phone: 800-522-7222 (toll-free)
Fax: 212-279-5999
Email: info@cooleyanemia.org
www.cooleysanemia.org

Thalassaemia International Federation (TIF)
PO Box 28807
Nicosia 2083 Cyprus
Phone: +357 22 319129
Fax: +357 22 314552
Email: thalassaemia@cytanet.com.cy
www.thalassaemia.org.cy

Thalassemia Patients and Friends provides discussion forums for questions and specific topics. thalpal

The Thalassemia Foundation of Canada provides events, news and research updates. thalassemia canada

Isabella’s Journey provides a long list of associations, organizations and resources from all parts of the world. Isabella’s Journey

Northern California Comprehensive Thalassemia Center is a thalassemia treatment center in Oakland, California that provides care and research for patients with thalassemia. No Calif Thalassemia Center
They also have a newsletter: No Calif Thalassemia Center Newsletter

The Vancouver Thalassemia Society of BC offers information and events: BC thalassemia

Thalassemia Support Foundation provides information. Helpthals

Thalassemia Action Group is a national peer support network of patients that provides information on thalassemia. They can be contacted at (800) 935-0024 or (800) 522-7222 (e-mail: ncaf@aol.com)
http://thalassemia.com/living-with-thal-stages-teen.aspx#gsc.tab=0

All forms of alpha-thalassemia are genetic. Alpha-thalassemia is caused by alterations or changes to the genetic instructions for an important protein in red blood cells, which carry oxygen to the cells of the body.

There are four different types of alpha-thalassemia. These include hemoglobin Bart (Hb Bart) disease, hemoglobin H (HbH) disease, alpha-thalassemia trait and alpha-thalassemia silent carriers. Each type includes a range of symptoms.

There are four types of alpha-thalassemia. These include hemoglobin Bart (Hb Bart) disease, hemoglobin H (HbH) disease, alpha-thalassemia trait and alpha-thalassemia silent carriers. The symptoms of alpha-thalassemia are variable, according to the severity of disease. Alpha-thalassemia is caused by mutations in the HBA1 and/or HBA2 genes. We each have two copies of HBA1 and HBA2, for a total of four copies.
Those who have no working copies or HBA1 or HBA2 have the most severe form, hemoglobin Bart syndrome. Symptoms begin prenatally and include swelling of the body, fluid surrounding the brain, heart and lungs, severe anemia, enlarged liver and spleen, heart defects and defects of the urinary and genital system. Death usually occurs in newborns. These pregnancies can be complicated by preeclampia (extreme hypertension), excessive amniotic fluid or reduced amniotic fluid, bleeding in the genital tract, and premature delivery.
The less severe form of alpha-thalassemia is called hemoglobin H disease. These individuals have one working copy of HBA1 or HBA2. Symptoms of this form vary from mild to more severe. Symptoms usually start by age one, but for some, symptoms do not begin until adulthood. Those with more severe symptoms can have anemia, enlarged spleen, gallstones, slowed growth and decreased bone density. 24% to 80% of these patients receive blood transfusions, and blood transfusions start between 0 and 3 years of age. Those with less severe symptoms are less like to receive blood transfusions, with 3% to 29% chance. The age at first blood transfusion is older, between 6 and 15 years of age. The anemia, enlarged spleen, gallstones, slowed growth and decreased bone density are more mild. Those with hemoglobin H disease may experience bone changes of the face, such as enlargement of the upper jaw, protruding of the forehead and enlargement of the cheekbones. In very severe cases, infants have died prenatally or soon after birth. The cause of this extreme variability is unknown.
Those with alpha-thalassemia trait have two working copies of HBA1 or HBA2. They have mild anemia. Silent carriers have three working copies or HBA1 or HBA2 and do not experience symptoms.
During pregnancy, women with hemoglobin H may experience more severe anemia. In the third trimester, increased rate of premature labor, preeclampsia and congestive heart failure have been reported.

Alpha-thalassemia can look like several other conditions described below.

The most severe form of alpha-thalassemia, hemoglobin Bart, results in a condition called hydrops fetalis, an accumulation of fluid in the fetus. Hydrops fetalis can occur as a result of many other conditions, including immune-related disorders, fetal heart abnormalities, chromosome abnormalities, fetal infections, genetic disorders, and maternal and placental disorders. A high level of a form of hemoglobin, called hemoglobin Barts, can distinguish alpha-thalassemia from these other conditions.

Alpha-thalassemia is associated with hemolytic anemia, a condition in which blood cells are prematurely destroyed, causing anemia. There are other conditions associated with hemolytic anemia, including hereditary spherocytosis/elliptocysosis and G6PD deficiency. Blood tests can distinguish these.

Alpha-thalassemia is associated with anemia. There are many causes of anemia. These include iron deficiency, B12 deficiency, and folate deficiency. Sideroblastic anemia is caused by the production of abnormal red blood cells.

A syndrome called alpha-thalassemia X-linked intellectual disability (ATRX) syndrome involves alpha-thalassemia. However, these individuals also have other symptoms, including distinct facial features, genital abnormalities, and severe developmental delay.

A similar blood condition is called beta-thalassemia. This disease also involves abnormal hemoglobin and symptoms including anemia, enlarged liver and spleen, delayed growth and the need for blood transfusions. Blood studies can distinguish between alpha and beta thalassemia. Other abnormalities of hemoglobin can look similar to alpha-thalassemia.

Lead poisoning can cause red blood cells to look smaller, similar to the red blood cells of those with alpha-thalassemia.

Blood cancers, such as leukemia, lymphoma and multiple myeloma can mimic alpha-thalassemia.