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DESCRIPTION
Other names this disease is known by:
Thalassemia major; Thalassemia; Mediterranean anemia; Cooley's anemia; Thalassemia intermedia
Clinical thalassemia (major and minor) are hereditary disorders characterized by defective production of hemoglobin, which leads to decreased production and increased destruction of red blood cells.
Thalassemia refers to a group of inherited anemias (red blood cell deficiency). It is a disease of hemoglobin, which is the protein which delivers oxygen throughout our bodies. It is estimated that 100,000 babies a year are born with severe forms, about 10,000 in India alone. Geographically the Thalassemia belt includes the Mediterranean passing through West and Central Asian countries like Turkey, Iran, Afghanistan onto Pakistan & India and passes on to the South East Asian countries like Indonesia, Burma & Thailand, Vietnam and Cambodia. This makes it most common in African, Greek, Italian, Middle Eastern and Southern Asian populations.
The two main groups of Thalassemia are called alpha and beta. There are four types of alpha Thalassemia and three types of beta Thalassemia.
ALPHA THALASSEMIA
Alpha Thalassemia genes are found in Southeast Asians, African blacks, Southeast Asia, Southern China, and people originally from the Middle East and occasionally the Mediterranean region. The disease affects the red blood cells in two ways. First the body cannot make enough cells with normal hemoglobin. Second, the cells have their lifespan shortened from four months to less than one month.
There are four types of alpha thalassemia that range from mild to severe in their effect on the body.
- The first type of alpha Thalassemia minor (trait) is a carrier state with no anemia and no symptoms.
- The second type has slightly abnormal red cells but still no anemia.
- The third type of alpha Thalassemia produces a mild anemia that generally does not lead to serious complications. The red blood cells are slightly abnormal and resemble iron deficiency anemia. These children would most likely have not been diagnosed and may present for adoption.
- The fourth type of alpha Thalassemia major is the most severe and affects mostly Southeast Asians, Chinese and Filipinos. It results in death before or soon after birth. This last type is usually seen only in Southeast Asians.
Silent Carrier State: This condition generally causes no health problems because the lack of alpha protein is so small that the hemoglobin functions normally. It is called "silent carrier" because of how difficult it is to detect. Silent carrier state is "diagnosed" by deduction when an apparently normal individual has a child with hemoglobin H disease or alpha thalassemia trait.
Hemoglobin Constant Spring: This is an unusual form of Silent Carrier state that is caused by a mutation of the alpha globin. It is called Constant Spring after the region of Jamaica in which it was discovered. As in silent carrier state, an individual with this condition usually experiences no related health problems.
Alpha Thalassemia Trait or Mild Alpha Thalassemia: In this condition, the lack of alpha protein is somewhat greater. Patients with this condition have smaller red blood cells and a mild anemia, although many patients do not experience symptoms. However, health care providers often mistake mild alpha thalassemia for iron deficiency anemia and prescribe iron supplements that have no effect on the anemia.
Hemoglobin H Disease: In this condition, the lack of alpha protein is great enough to cause severe anemia and serious health problems such as an enlarged spleen, bone deformities and fatigue. It is named for the abnormal hemoglobin H (created by the remaining beta globin) that destroys red blood cells.
Hemoglobin H-Constant Spring: This condition is more severe than hemoglobin H disease. Individuals with this condition tend to have a more severe anemia and suffer more frequently from enlargement of the spleen and viral infections.
Homozygous Constant Spring: This condition is a variation of hemoglobin H-Constant Spring that occurs when two Constant Spring carriers pass their genes on to their child (as opposed to hemoglobin H Constant Spring, in which one parent is a Constant Spring Carrier and the other a carrier of alpha thalassemia trait). This condition is generally less severe than hemoglobin H Constant Spring and more similar to hemoglobin H disease.
Hydrops Fetalis or Alpha Thalassemia Major In this condition, there are no alpha genes in the individual's DNA, which causes the gamma globins produced by the fetus to form an abnormal hemoglobin called hemoglobin Barts. Most individuals with this condition die before or shortly after birth. In some extremely rare cases where the condition is discovered before birth, in utero blood transfusions have allowed the birth of children with hydrops fetalis who then require lifelong blood transfusions and medical care.
BETA THALASSEMIA
Beta Thalassemia cause a broad range of health symptoms which range from none to very severe. Beta Thalassemia genes are more widespread - found in Africa, the Middle East, the Arabian Peninsula, Iran, India, Southeast Asia, and around the Mediterranean, such as Italians and Greeks and Southern China. Someone with only one of the beta genes will have beta Thalassemia trait, a mild anemia in which the red cells are smaller than normal. Because small red cells are also typical of iron deficiency anemia, which is extremely common in women and children, many people with this trait are erroneously diagnosed as iron deficient, and are given iron pills. Iron not only does not help this mild anemia, but it can build up in the tissues.
The three categories of beta Thalassemia are minor, intermedia and major.
Beta Thalassemia minor (Thalassemia trait): This form may cause no symptoms, but can be identified by changes in the blood. Children with Thalassemia minor (Thalassemia trait) are considered carriers and lead completely normal, healthy lives. Beta Thalassemia intermedia is a mild form of Cooley's anemia.
In this condition, the lack of beta protein is not great enough to cause problems in the normal functioning of the hemoglobin. A person with this condition simply carries the genetic trait for thalassemia and will usually experience no health problems other than a possible mild anemia. As in mild alpha thalassemia, health care providers often mistake the small red blood cells of the person with beta thalassemia minor as a sign of iron-deficiency anemia and incorrectly prescribe iron supplements.
Thalassemia Intermedia. Children with Thalassemia intermedia may develop similar complications, but usually the disease is mild until adulthood. These children usually do not require transfusions, although they may be recommended if complications start to develop. However, countries such as Vietnam which permit the adoption of very young infants may not have identified these children prior to adoption.
In this condition the lack of beta protein in the hemoglobin is great enough to cause a moderately severe anemia and significant health problems, including bone deformities and enlargement of the spleen. However, there is a wide range in the clinical severity of this condition, and the borderline between thalassemia intermedia and the most severe form, thalassemia major, can be confusing. The deciding factor seems to be the amount of blood transfusions required by the patient. The more dependent the patient is on blood transfusions, the more likely he or she is to be classified as thalassemia major. Generally speaking, patients with thalassemia intermedia need blood transfusions to improve their quality of life, but not in order to survive.
Thalassemia major (Cooley's anemia): This is the most severe form of beta thalassemia in which the complete lack of beta protein in the hemoglobin causes a life-threatening anemia that requires regular blood transfusions and extensive ongoing medical care. These extensive, lifelong blood transfusions lead to iron-overload which must be treated with chelation therapy to prevent early death from organ failure.
Infants with Thalassemia major appear healthy at birth, but develop symptoms around 8 to 10 months of age. These children appear pale, weak, fussy, and have poor appetites. Their growth is slow and they often become jaundiced. Left untreated, the spleen, liver, and heart soon begin to fail. Bones become thin and brittle, and facial bones become misshapen. Untreated children experience retarded physical and mental growth. In untreated children, heart failure and infection are the leading causes of death.
OTHER FORMS OF THALASSEMIA
In addition to the alpha and beta thalassemias, there are other related disorders that occur when the gene for alpha or beta thalassemia combines with an abnormal or mutant gene.
E Beta Thalassemia: Hemoglobin E is one of the most common abnormal hemoglobins. It is usually found in people of Southeast Asian ancestry, such as Cambodians, Vietnamese and Thai. When combined with beta thalassemia, hemoglobin E produces E beta thalassemia, a moderately severe anemia which is similar in symptoms to beta thalassemia intermedia.
Sickle Beta Thalassemia: This condition is caused by a combination of beta thalassemia and hemoglobin S, the abnormal hemoglobin found in people with sickle cell disease. It is commonly found in people of Mediterranean ancestry, such as Italians, Greeks and Turks. The condition varies according to the amount of normal beta globin produced by the beta gene. When no beta globin is produced by the beta gene, the condition is almost identical with sickle cell disease. The more beta globin produced by the beta gene, the less severe the condition.
FREQUENT SIGNS & SYMPTOMS
Fatigue. Shortness of breath. Jaundice. Bony deformities (mongoloid appearing faces). Enlarged spleen. Peripheral blood smear shows small, abnormally-shaped red blood cells. Complete blood count shows anemia. Hemoglobin electrophoresis shows abnormal hemoglobin.
This disease may also alter the results of the following tests:
RBC indices (size, hemoglobin content). Osmotic fragility.
CAUSES & RISK FACTORS
An imbalance in the alpha and beta globin chains necessary for the production of hemoglobin is caused by the inheritance of a defective gene. There are two types of thalassemia, alpha thalassemia and beta thalassemia.
Genes must be inherited from both parents to acquire the disease. If one gene is inherited, the person will be a carrier of the disease, but will not have symptoms.
Alpha thalassemia's occur most commonly in people from southeast Asia and China, and are caused by deletion of a gene or genes from the globin chain. The most severe form of alpha thalassemia causes a stillborn fetus.
Beta thalassemia occurs in people of Mediterranean origin, and to a lesser extent, Chinese, other Asians, and blacks. It is caused by a mutation in the beta globin chain. Affected children are normal at birth, but develop anemia during the first year of life.
Growth failure, bone deformities, and enlarged liver and spleen are some of the problems that can occur. Blood transfusions may modify some of the disease manifestation, but iron overload from the transfusions can cause damage to the heart, liver, and endocrine systems.
A milder form of the disease, thalassemia minor, produces small red blood cells, with no symptoms. Risk factors include a family history of thalassemia and an ethnic background susceptible to the disease. The incidence varies widely throughout the world.
PREVENTION
There is no way to prevent thalassemia once the child is born.
Genetic counseling may be helpful to couples with a family history of known thalassemia. There is a 25 percent chance with each pregnancy that a child will be born with thalassemia major if both parents carry the gene for thalassemia according to the western data.
Prenatal screening may be recommended for couples with a family history of thalassemia.
EXPECTED OUTCOME
In severe thalassemia, death from heart failure can occur between the ages or 20 and 30. Hypertransfusion programs with chelation therapy improve outcome, and successful bone marrow transplantation is curative. Less severe forms of thalassemia usually do not impact on life span.
POSSIBLE COMPLICATIONS
Untreated, thalassemia major leads to heart failure as well as liver dysfunction, and susceptibility to infection.
Iron overload as a side effect of treatment can cause damage to the heart, liver, and endocrine systems. This complication is managed by daily injections of an iron chelating agent which binds iron to it and causes it to be excreted in the urine.
TREATMENT
DIAGNOSIS
To understand how thalassemia affects the human body, you must first understand a little about how blood is made. Hemoglobin is the oxygen-carrying component of the red blood cells. It consists of two different proteins, an alpha and a beta. If the body doesn't produce enough of either of these two proteins, the red blood cells do not form properly and cannot carry sufficient oxygen. The result is anemia that begins in early childhood and lasts throughout life. Since thalassemia is not a single disorder but a group of related disorders that affect the human body in similar ways, it is important to understand the differences between the various types of thalassemia.
WHO CARRIES THE THALASSEMIA TRAIT?
Thalassemia was originally believed to be common only to people of the Mediterranean region, such as Italians, Greeks and Turks. (An early name for thalassemia major, or Cooley's anemia, was Mediterranean fever).
Since then, scientists have discovered that the thalassemia trait is found in people of many other regions, including the Arabian Peninsula, Africa, The Indian subcontinent, China and Southeast Asia.
Today, due to the migration and intermarriage of different ethnic populations, the trait for thalassemia is found throughout the world, sometimes in people with no obvious ethnic connection to the disorder.
It is estimated that over 2 million people in the United States carry the genetic trait for thalassemia. For this reason, the National Institutes of Health recommend that all US citizens should be tested for the thalassemia trait.
INHERITANCE OF THALASSEMIA
If two people who carry the trait for the same genetic type of thalassemia (alpha or beta) have a child, there is a 25 percent chance with each pregnancy that the child will inherit a serious blood disease.
If both parents carry the genetic trait for beta thalassemia, there is a 25 percent chance with each pregnancy that their child will be born with thalassemia major or Cooley's anemia, a fatal blood disease.
If one parent carries the trait for beta thalassemia and the other carries the trait for hemoglobin E, there is a 25 percent chance with each pregnancy that the child will be born with E beta thalassemia.
If one parent carries the trait for beta thalassemia and the other carries the trait for hemoglobin S, there is a 25 percent chance with each pregnancy that their child will be born with beta sickle thalassemia.
If both parents carry the trait for alpha thalassemia and if only one parent has the "cis" type of alpha trait (two alpha globin mutations on the same chromosome), there is a 25 percent chance with each pregnancy that their child will be born with hemoglobin H disease.
If both parents carry the trait for alpha thalassemia and if both parents have the "cis" type of alpha trait (two alpha globin mutations on the same chromosome), there is a 25 percent chance with each pregnancy that their child will inherit hydrops fetalis.
If one parent carries a thalassemia trait and the other parent has normal hemoglobin, there is no chance that the child will inherit a blood disease. However, there is a 25 percent chance that the child will inherit the thalassemia trait.
As you can see, the possibilities for inheriting the various forms of thalassemia are very complicated. Therefore, if you belong to any of the ethnic groups at risk, we recommend that you be tested for the thalassemia trait and, if you are found to be a trait carrier, seek the advice of a genetic counselor.
THALASSEMIA TRAIT TESTING
Finding out if you have the genetic trait for thalassemia begins by determining the size of your red blood cells.
If you have a routine blood test known as a Complete Blood Count, or CBC, already on file at your health care provider's office, ask your health care provider to look at the Mean Corpuscular Volume, or MCV. The MCV reading determines the size of your red blood cells. For adults, if the MCV reading is less than 75 you may be a trait carrier. For children, the MCV reading may be lower and varied according to their age.
If your MCV reading indicates that you may have the thalassemia trait, your health care provider should then perform additional tests to make sure.
Although the MCV reading is a good indicator of whether a person may have either the alpha or the beta thalassemia trait, finding out for certain if you have either trait involves two different kinds of tests.
A special test called hemoglobin electrophoresis is a reliable way of determining whether or not a person has the trait for beta thalassemia. This test is available at most large hospitals and clinics, including the thalassemia treatment centers listed on this website.
The trait for alpha thalassemia (or Silent Carrier) is much more difficult to identify and can only be determined by a special DNA test called alpha globin DNA mutation analysis. This test is available at only a few major medical centers in the US. If you suspect that you may have the alpha thalassemia trait and cannot visit one of those centers, your health care provider can send your blood sample to one of the special laboratories for DNA testing.
GENERAL MEASURES - CONVENTIONAL MEDICAL TREATMENT
DIAGNOSIS - BLOOD TESTS
All Thalassemias are inherited. People unfamiliar with the disease may mistakenly think it can be caught from another child. Blood tests can show whether an adopted child has Thalassemia or is a carrier. Identification of mild forms of the disease is important as well meaning health care providers may prescribe vitamins or food supplements containing additional iron. While this is appropriate for iron deficiency anemia, it can cause iron overload in children with any form of Thalassemia. There is now a simple test for iron in the body called the ferritin level. If someone seems to be iron deficient, but the ferritin level is normal, they probably have the first type of beta Thalassemia. Ask your health care provider to test your child's ferritin level if they are anemic before prescribing vitamins.
The blood tests used in helping to diagnose Thalassemia are:
- Blood count.
- Blood Film.
- Saturated iron binding capacity of serum ferritin levels.
- Hemoglobin electrophoresis.
TREATMENT OVERVIEW
With severe thalassemia, regular blood transfusions and folate supplementation are given. People who receive the blood transfusions should avoid iron supplements and oxidative drugs such as sulfonamides, because iron levels can become toxic.
Patients who receive significant numbers of blood transfusions require therapy to remove iron from the body, called chelation therapy. Bone marrow transplant is being investigated as a treatment and is most successful in children.
BLOOD TRANSFUSION TREATMENTS
Treatment with frequent blood transfusions and antibiotics can alter the course of the illness. Children with Thalassemia major can be treated by hypertransfusion. Transfusions every 3 or 4 weeks help keep their hemoglobin near normal. Today, most patients with a major form of thalassemia receive red blood cell transfusions every two to three weeks, amounting to as much as 52 pints of blood a year. This helps prevent some of the complications of the disease, resulting in better growth and general health and can prevent heart failure and bone deformities in some cases.
IRON OVERLOAD
Unfortunately, the treatments have their own drawbacks. Repeated blood transfusions lead to a buildup of iron in the body, damaging the heart, liver and other organs. Iron overload typically results in the patient's early death from organ failure. This requires daily drug treatment with a chelator to eliminate iron, preventing or delaying problems related to iron overload. The chelator drug is requires daily dosing given by pumping the drug underneath the skin while the child is sleeping.
Children treated aggressively with frequent blood transfusions and iron chelation live 20 to 30 years or longer.
MoonDragon's Health & Wellness: Iron Toxicity
BONE MARROW TRANSPLANTS (BMT) TREATMENTS
Bone marrow transplants (BMT) have cured some cases of Thalassemia. This high risk treatment is possible only for a small minority of patients as a suitable bone marrow donor must be located. The transplant procedure is still risky and can result in death. The success rate of BMT is as high as 95 percent, if there is no prior serious organ damage such as excess deposition of iron. About one-third of all BMT patients will have a siblings whose bone marrow is a good match. Adopted children lacking an identifiable common gene pool of their birth family would be less likely to find a suitable donor than a child with an intact and identifiable birth family.
Transplantation: To better understand transplantation, you must first understand the important role played by the blood stem cell. Blood stem cells are responsible for producing all of a person's blood cells. It is the stem cells, located in the bone marrow, that give rise to all of the red blood cells that produce hemoglobin, the oxygen-carrying component of blood. In the case of thalassemia, it's the defect in the stem cells that leads to the misshapen red blood cells that produce the abnormal hemoglobin and transfusion-dependent anemia.
The fundamental goal of transplantation is to provide the thalassemia patient with healthy stem cells that will lead to the production of normal red blood cells and normal hemoglobin.
Researchers attempt to introduce healthy stem cells into the patient's body through a variety of means:
Bone Marrow Transplantation: In bone marrow transplantation (BMT), chemotherapy is used to kill the patient's stem cells in the bone marrow. The patient's own stem cells are then replaced with healthy stem cells from a compatible donor. If the procedure is successful, the transplanted blood stem cells in the bone marrow begin making normal blood cells.
One problem with bone marrow transplantation is the difficulty of finding a compatible donor.
Unlike bone marrow transplantation for cancer patients which requires only a "close" or "best" match, bone marrow transplantation for thalassemia requires a perfect genetic match, usually found in the patient's sibling or other family member. According to the National Heart, Lung and Blood Institute (NHLBI), 60 percent of children with thalassemia in the United States do not have a sibling or family member who is genetically compatible.
For patients who do not have a genetically compatible sibling, an unrelated volunteer donor is the next best option. "Marrow registries" provide patients with a way of locating the most compatible unrelated volunteer donors. One such registry is the National Marrow Donor Program (NMDP) that lists 1.6 million volunteer donors.
Bone marrow transplants are generally most successful when the donor and host are as genetically compatible as possible, and when the patient is younger and less transfused.
The more genetically mismatched the donor and host, the greater the likelihood of rejection.
The most important risk of bone marrow transplantation from unrelated donors is Graft-Versus-Host Disease (GVHD). GVHD is an immunological response in which the donor's immune system (present in the donated cells) attacks the host's tissues. In its most serious form, GVHD can be fatal.
There is also a lesser risk of the host's immunological system rejecting the donor's stem cells, or Host-Versus-Graft (HVG) reaction.
Technically, transfusion-dependent anemia in thalassemia can be cured by bone marrow transplantation (BMT). However, for the reasons cited above, BMT remains an extremely risky and problematic procedure that is not a practical option for the majority of thalassemia patients.
Mixed chimerism is an alternate approach to bone marrow transplantation in which the patient's own thalassemic stem cells are not entirely eliminated but exist alongside of the transplanted "healthy" stem cells. This approach significantly reduces some of the risks associated with traditional bone marrow transplantation. This procedure is being studied experimentally at the present time in patients with cancer.
Cord Blood Transplantation: Cord Blood Transplantation is an alternate means of transplanting healthy stem cells into the thalassemia patient's body. Instead of harvesting stem cells from a donor's bone marrow or blood, stem cells are taken from the "cord blood" found in the umbilical cord and placenta of a newborn sibling.
Cord blood is taken from the umbilical cord and placenta immediately following birth and then frozen and stored at a cord blood center for later use in stem cell transplantation.
The advantage of using cord blood is that, unlike "regular" bone marrow transplantation, the stem cells taken from cord blood do not have to be a perfect genetic match. As such, there appears to be a lower instance of rejection in cord blood transplantation.
OTHER POSSIBLE TREATMENTS - CHELATION THERAPY & GENE THERAPY
Other treatments are being researched and used include oral chelating drugs and various types of gene therapy, including stem cell transplants (see above).
Chelation Therapy: To help remove excess iron, patients undergo the difficult and painful infusion of a drug, Desferal. A needle is attached to a small battery-operated infusion pump and worn under the skin of the stomach or legs five to seven times a week for up to twelve hours. Desferal binds iron in a process called "chelation." Chelated iron is later eliminated, reducing the amount of stored iron.
Compliance with Desferal is vital to the thalassemia patient's long term survival. However, many patients find the treatment so difficult that they do not keep up with it or abandon treatment altogether. Lack of compliance with chelation therapy leads to accelerated health problems and early death. To combat the compliance problem, researchers are at work on less stressful new chelators that can improve patient compliance. They are developing and testing the effectiveness of oral iron-chelating drugs, which could greatly simplify treatment of this disease.
March of Dimes grantees are among the many scientists seeking to develop an effective form of gene therapy that may someday offer a cure for thalassemia. Gene therapy may involve inserting a normal beta globin gene (the gene that is abnormal in this disease) into the patient's stem cells, the immature bone marrow cells that are the precursors of all other cells in the blood. Another form of gene therapy may involve using drugs or other methods to reactivate the patient's genes for fetal hemoglobin. All humans produce a fetal form of hemoglobin before birth; after birth, natural genetic switches "turn off" production of fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to activate these genetic switches so that they can make the blood cells of patients with thalassemia produce more fetal hemoglobin to compensate for their deficiency of adult hemoglobin. Initial studies of rare individuals with genetic traits that allow them to produce only fetal hemoglobin show that they are generally healthy, demonstrating that fetal hemoglobin can be a fine substitute for adult hemoglobin.
Gene Therapy: Unlike the different forms of stem cell transplantation that attempt to correct thalassemia by replacing the patient's stem cells with healthy ones from a donor, gene therapy (also known as gene replacement therapy) attempts to "fix" the patient's own stem cells by replacing defective genes with normal ones.
To correct transfusion-dependent anemia in thalassemia, the objective of gene therapy is to insert a normal beta globin gene into the patient's stem cells, thus allowing for increased production of beta globin and the production of healthy red blood cells.
Gene therapy is still far from being applied to human subjects in a clinical setting. Before gene therapy can become a practical reality for thalassemia patients, researchers must first overcome some difficult challenges:
- One problem is with the behavior of the stem cells themselves. Stem cells tend to behave differently in laboratory cultures outside the human body and lose their ability to reproduce over long periods of time. Scientists must find ways of helping stem cells keep their reproductive capabilities in research settings.
- Another problem centers on the actual means of transferring the "replacement gene" into the stem cells. Currently, the methods used to transfer the replacement gene into stem cells require the cell to be actively dividing. Most stem cells are in their non-dividing phase most of the time and thus are not receptive to gene transfer.
Researchers have induced stem cells to divide in order to make more frequent gene transfer possible, but the results have largely been unsuccessful.
Researchers are now working on methods that may allow gene transfer while the stem cell is not dividing.
Fetal Hemoglobin Manipulation: Before birth, human blood is made up of alpha globin that it will have throughout life and gamma globin that exists primarily during fetal life. Shortly before birth, a change known as the "hemoglobin switch" takes place, in which gamma globin decreases and is replaced by an increase in beta globin, thereby changing fetal hemoglobin into adult hemoglobin.
In infants with thalassemia intermedia or major, the beta globin fails to "turn on" properly, and the resulting imbalance in beta and alpha globin causes transfusion-dependent anemia.
The theory behind fetal hemoglobin manipulation is that if the "hemoglobin switch" can be delayed or reversed and fetal hemoglobin production can be maintained or turned back on, then the transfusion-dependent anemia caused by the defective beta genes can be reduced or eliminated.
Fetal Hemoglobin Manipulation by Drugs: Researchers have discovered that fetal hemoglobin production can be induced in adult beta-thalassemia patients through the application of three kinds of drugs: cytoxic agents such as hydroxyurea, recombinant hematopoietic growth factors such as erythropoitin, and fatty acid analogs such as arginine butyrate.
Although the increase in fetal hemoglobin made possible by these drugs has been shown to reduce anemia in thalassemia major patients, these reductions have been mostly marginal and not great enough to make thalassemia major patients transfusion-independent. Researchers are at work on other, more effective ways of increasing the production of fetal hemoglobin.
Genetic Manipulation of Fetal Hemoglobin: This approach focuses on finding and manipulating the genetic factors responsible for the "hemoglobin switch" from fetal hemoglobin to adult hemoglobin.
Researchers are seeking a reliable method of reactivating the gamma-globin genes that are "turned off" during the switch from fetal to adult hemoglobin.
Before fetal hemoglobin manipulation can become a viable therapy for thalassemia, more clinical trials are needed to test the safety and effectiveness of the drugs that stimulate the production of fetal hemoglobin, and more research is required for researchers to fully understand the genetic factors and molecular events responsible for the hemoglobin switch.
Summary: Although transfusion-dependent anemia in thalassemia can technically be cured by bone marrow transplantation (BMT), BMT remains a risky and problematic procedure that is not a realistic option for the majority of thalassemia patients.
Alternate approaches to stem cell transplantation such as mixed chimerism and cord blood transplantation have reduced some of the risks associated with transplantation, but have yet to succeed in developing a safe, effective and affordable curative therapy for thalassemia.
Fetal hemoglobin manipulation has been shown to reduce the need for blood transfusions in some forms of thalassemia somewhat but has so far been unable to eliminate the need for transfusions. Finally, gene therapy, although promising, is still not an available therapeutic option.
Further research and clinical trials are needed in all these areas before thalassemia can be said to be a curable disease.
LINKS TO WEB SITES ABOUT THALASSEMIA
www.cooleysanemia.org
March of Dimes: Thalassemia
Northern California Thalassemia Center
DIET
DIET RECOMMENDATIONS FOR THALASSEMIA
Reducing the Iron Absorbed from Food
by Dr. Dona Hileti-Tefler
www.thalassemia.org
Thalassemia is a complex condition and the ideal diet would need to take account of many factors. This article concerns the iron present in food. Subsequent articles will discuss antioxidants in food, diet for the prevention of osteoporosis and diabetes, zinc in the diet and diet for children with thalassemia.
In thalassemia, although most of the iron overload is due to blood transfusion, increased absorption of iron from the diet is also important. Only a small amount of iron from the diet is absorbed into the body. The amount absorbed is higher when hemoglobin in the blood is low. People with low hemoglobin such as those with thalassemia intermedia or those with thalassemia major, in between transfusions could therefore adapt their diet so that not only the total amount of iron in their diet is low but also the amount of iron in their body is low.
There are two kinds of iron in the diet: iron which is present in red meat (meat iron) and iron which is widely distributed in the diet (non-meat iron).
Meat Iron:
Meat iron is present in red meat such as beef, lamb, pork and the dark meat of chicken as well as in seafood such as sardines, cockles and mussels. Liver is a very rich source of meat iron. Try to cut down on these and perhaps substitute meat with soy protein. It is not, however, a good idea to exclude meat, chicken and fish completely from your diet because they contain other important nutrients, particularly for children. Choose the white part of the chicken rather than red meat as this contains less iron.
On average, after a meal with red meat, about 35 percent of iron will be absorbed into the body. However, this may vary between 10-40 percent, depending mainly on whether the meal contains milk or milk products. The calcium present in milk, cheese, yogurt and cream decreases the absorption of meat iron. Try to drink a glass of milk with a meat-containing meal and to use milk in cooking. Good examples are the white cheesy sauces in lasagna, pasticcio, mousaka and cannelloni, adding lots of cheese in spaghetti bolognese and using yogurt and milk to cook your curries.
Milk intake should be at least one pint daily, particularly because it helps to prevent osteoporosis, as will be discussed later. If you are worried about your weight, semi-skimmed milk or skimmed milk are just as rich sources of calcium as whole milk.
Non-meat Iron:
Non-meat iron is widely distributed in the diet, present in eggs, chocolate, cereals, vegetables, fruits, roots (potatoes, parsnips), beans and lentils. In the U.K., several foods are fortified with iron, such as breakfast cereals, wheat flour and bread. However, this may not be the case in other countries.
The absorption of non-meat iron from the diet into the body is much less than that of meat iron, but it may vary more than twenty fold, depending on the composition of a meal. The foods which decrease its absorption are (i) cereals and (ii) dairy products. The foods which increase its absorption are (i) fruits and vegetables rich in vitamin C, (ii) meat, fish, shellfish and poultry, and (iii) pickles, sauerkraut, soy sauce, vinegar and alcohol.
It is difficult to avoid taking non-meat iron because it is present in most foods. However, diets can be modified by taking more of the foods which decrease and less of the foods which increase the amount of iron absorbed into the body. These foods will be discussed below.
Foods Which Decrease Non-meat Iron Absorption:
Cereals - Wheat bran, maize, oats, rice and soy decrease the iron absorbed into the body and fight the effect of vitamin C. Foods rich in vitamin C increase iron absorption. It is good to include a lot of cereals in your diet, but remember not to take a vitamin C-rich food with them, like orange juice. Try to combine milk and cereals (e.g., cheese sandwich, French toast, macaroni and cheese, cereals and milk). In the U.K., all wheat flour other than whole meal is required by law to be fortified with iron. The fortification of breakfast cereals is voluntary. It may therefore be better to choose unfortified whole meal what flour bread and to look carefully at the label of your favorite breakfast cereal. Unfortified breakfast cereals include porridge oats and some cereals in health shops, but look at the label to make sure you choose an unfortified variety. In other countries, flour and breakfast cereals may not be fortified.
Soy protein also decreases the amount of iron absorbed into your body. Soy protein can work well in many recipes (e.g., spaghetti bolognese, stews and casseroles) and the taste can be improved by adding spices.
Tea, Coffee and Spices - Tea, coffee and some spices (e.g., oregano) decrease iron absorption. Drink plenty of tea and coffee daily, particularly with your meals. Better yet, if you take it with milk. Tea is also a very good source of antioxidants, as will be discussed later. And keep adding oregano to spice up your souvlaki!
Dairy Products - Milk, cheese and yogurt decrease the iron absorbed into the body. Calcium is also important for osteoporosis, so it is good to include as many dairy products as you can in your diet. Lower fat varieties of milk (skimmed or semi-skimmed) and cheese are just as high in calcium and may be preferred if you are watching your weight. At least one pint of milk should be taken every day.
Foods Which Increase Non-Meat Absorption:
Vitamin C - Vitamin C is present in fruit, fruit juice and vegetables. It is better to avoid drinking fruit juice, such as orange juice, with your meal or your toast in the morning. Instead, a cup of tea or coffee is a better option as they inhibit iron absorption. Alternatively, have a glass of milk! Beer increases iron absorption, so it is better to avoid drinking it with your meal too often, but you could always have it on its own with some nuts. Fruit and fruit juice are, however, good sources of antioxidants and should be taken on their own as snacks. Boiled vegetables contain much less vitamin C because the vitamin leaks into the water.
Meat, Poultry, Fish and Seafood - Meat, poultry, fish and seafood not only contain a lot of meat iron but they also help to absorb more of the non-meat iron from your food. It would be unwise, however, to omit them from the diet altogether, as they contain other vital nutrients, particularly important for children and adolescents.
Pickles, Sauerkraut, Soy Sauce, Vinegar and Alcohol - Sauerkraut, pickled onions, turnips and carrots, as well as fermented soy products (e.g., miso and soy sauce) enhance iron absorption. The amount of iron absorbed is even higher when the pickled vegetables are added to bread and rye-containing meals.
In general, a low iron diet would contain cereals (maize, whole-grain flour, beans) and root vegetables with little meat, fish or foods rich in vitamin C. A moderate iron diet would consist of cereals and root vegetables, but would also contain some vitamin C-rich foods and meat. A high iron diet contains generous quantities of meat, poultry and fish. They also contain foods with high levels of vitamin C, such as citrus fruits and some vegetables. A high iron diet can be reduced to a moderate one by the regular consumption of foods which decrease the amount of iron absorbed by the body, such as dairy products, cereals, beans, coffee and tea.
Antioxidants in Food:
Paradoxically, oxygen is essential for life but is also lethal! This is because normal oxygen molecules can convert into different chemical forms known as "free radicals." When the activity of free radicals is harnessed and controlled, they have important uses in the body. Uncontrolled free radicals, however, can do great damage and lead to disease.
Antioxidants are important in any diet, because as their name suggests, they prevent oxidative damage in the body. In doing so, they play an important role in the prevention of diseases such as coronary heart disease and cancer.
In thalassemia, because of the excess iron in the body, there is a higher risk of oxidative damage. In this article, I will concentrate on the four main antioxidants: vitamin E, vitamin C, carotenoids and flavonoids.
Vitamin E - Vitamin E is the most important dietary antioxidant. Several studies have found that many thalassemics have lower levels of vitamin E in their blood compared to non-thalassemics. This could be either because thalassemics do not take as much vitamin E in their diet or because their needs are higher. In many studies, when vitamin E was given as a supplement, vitamin E levels in the blood improved. However, even if your health care provider or dietician recommends that you take a supplement, the best way for any vitamin to enter your body is through your food.
Vitamin E is fat-soluble, which means that it is present in foods that have a high amount of fat. The best sources of vitamin E are vegetable oils (olive, safflower, palm and soya oil). The best one to use is probably olive oil because the type of fat it contains can help to prevent heart disease. In Mediterranean countries where olive oil is used a lot (Greece, Portugal, Spain and Italy), heart disease is lower than in northern Europe. Remember, however, that the vitamin is destroyed slowly with frying. Therefore, the best way to get the most out of your olive oil is to add it to foods towards the end of cooking or even after it is cooked, as a dressing. Olive oil mixed with lemon, for example, can make a delicious dressing for fish, chicken, boiled vegetables and salads. Being Greek Cypriot myself, I can give you many recipes which feature olive oil as the main ingredient! You can probably do better, however, using your own imagination. Choose the extra virgin olive oil if you like the intense flavor and you tend to use it as a dressing, or experiment with more refined varieties if you want to use it for cooking, making cakes, etc. Ghee also contains vitamin E but since olive oil has additional health benefits, you may like to try using it in cooking.
Other sources of vitamin E are dairy products, cereals, nuts, eggs and meat. Dairy products are particularly good to include in the diet not only because they contain vitamin E but also because they inhibit iron absorption from our food into our bodies and also because they contain a lot of calcium which can help to prevent osteoporosis (weak bones). You can try to use milk in cooking or to have a glass of milk with your meal. Skimmed milk has lower levels of vitamin E than full-cream milk, although the amount of calcium is the same.
Vitamin C - You might remember from my previous article that vitamin C increases the absorption of non-meat iron. Therefore, although vitamin C is a very powerful antioxidant, I will not advocate the use of many foods containing vitamin C in combination with foods that are high in non-meat iron. This is important for those with thalassemia intermedia who are not regularly transfused.
Remember that non-meat iron is widely distributed in the diet, present in eggs, chocolate, cereals, vegetables, fruits, roots (potatoes, parsnips), beans and lentils. In the United Kingdom, several foods are fortified with iron, such as breakfast cereals, wheat flour and bread, although this may not be the case in other countries.
Vitamin C is mainly found in fruit, fruits juices and vegetables. It might be better to have your piece of fruit or glass of fruit juice on its own, in between meals and not during or immediately after your meal. As health professionals, we recommend people eat 5 portions of fruit and vegetables daily.
Examples of what constitutes one portion are: a glass of fruit juice; a piece of fruit such as an apple, pear, banana, orange, half a grapefruit, one tomato; a helping of vegetables such as carrots, courgettes, French beans or a small salad. Vitamin C is water-soluble, so if vegetables are boiled it will leak out in the water. Light steaming preserves the vitamin better. Cooked vegetables with olive oil and lemon can make a very tasty snack or a light meal. Vitamin E and vitamin C work better when they are together, so remember to fuel your vegetables with olive oil!
Carotenoids - Common dietary sources of carotenoids are carrots, yellow squash, corn, tomatoes, papaya, oranges and dark-green leafy vegetables. Again, most of these foods are high in vitamin C and therefore the same caution applies as above. It is worth pointing out that the absorption of carotenoids from the diet is much higher when the food contains fat or oil. So keep adding that olive oil! Carotenoids can be destroyed at high temperatures so keep the cooking temperature low and the time short if you can.
Flavonoids - These are found in tea, red wine, fruit and vegetables. What better excuse to include a glass of red win with your meal! If it is a more sober occasion, have your meal with a cup of tea! (I am sure the English amongst you are now rejoicing.) It took my English husband several years of hard work and gentle persuasion to convince me to have tea more often than once every three months (usually when I have a cold). Tea will not only give you lots of antioxidants, but it will also inhibit the absorption of iron from your food, especially if you take it with milk. Try to have several cups of tea daily. Remember that we need about 8 glasses of fluid daily to be well hydrated.
(Dr. Dona Hileti-Telfer is Senior Dietician at the Great Ormond Street Hospital for Sick Children in London. This article is reprinted from Thalassemia International Federation Magazine and from the UK Thalassemia Society newsletter.)
DIET FOR THE NON-TRANSFUSED PATIENT
Non-transfused thalassemia intermedia patients are encouraged to avoid high-iron and iron-supplemented foods, and encouraged to drink tea with meals, which decreases iron absorption. Serum ferritin is evaluated in adolescents. Desferrioxamine is instituted early in the development of hemosiderosis. Iron overloaded individuals receive a liver biopsy. Early cardiac evaluation with Holter monitoring and stress ECHO cardiogram is done in individuals with significant hemosiderosis. In addition, folic acid deficiency appears to be more common in these individuals.
LOW IRON DIET FOR THE CHRONICALLY-TRANSFUSED PATIENT
Regular blood transfusions can lead to iron overload in the body. Extra iron from chronic transfusions is stored in the liver. Once the liver stores are full, the iron begins to accumulate in places like the heart and pituitary, where it can do damage. Iron overload can also result from increased absorption of iron from the gut, as can be the case with thalassemia intermedia. To help keep the iron stores from building up too fast, a medication called Desferal may be used in conjunction with a low iron diet. Keep the iron under 10 mg/day for those children under 10 years old, and under 18 mg/day for those who are 11 years old and older.
Children who have thalassemia and are transfused are still relatively anemic, so their bodies might still crave iron. As it may be difficult to watch their diets closely, they should develop good habits early. Remind children to definitely avoid very high iron foods such as dried beef and other high iron beef products, even if they are craving it. Remember that the iron found in meat is much more easily absorbed than other sources of iron, such as cereals and breads.
Do not cook with cast iron cookware (e.g. a wok) because iron from the cookware can transfer onto the food. Some foods, such as orange juice, can enhance iron absorption, while others, like tea, dairy and coffee, can decrease absorption. If you are using Desferal, however, it is recommended that you take 250 mg or less of vitamin C after beginning infusion to help increase output of iron.
On food labels, the percentage of iron in one serving of that food is usually listed. This is based on the U.S. Recommended Daily Allowance of 18 mg/day. If the label says the food contains 8 percent of the daily recommended iron, multiply 0.08 by 18 mg to get the mg iron from a serving of that food. Don't forget to check candy bars and snacks!
LOW IRON DIET FOR THE CHRONICALLY-TRANSFUSED PATIENT
Very high iron sources are found in the following foods; they should be avoided or eliminated from the diet:
Proteins that should be avoided or eliminated from the diet:
- Oysters
- Liver
- Pork
- Beans
- Beef
- Peanut butter
- Tofu
Grains that should be avoided or eliminated from the diet:
- Flour tortillas
- Infant cereal
- Cream of wheat
- Malt-O-Meal
- Cereals, such as Most, Product 19, Total, Kix, All Bran, Life, Raisin Bran, Special K, 100% Bran, Rice Chex, Rice Krispies, Cornflakes, Wheaties
Fruits/Vegetables that should be avoided or eliminated from the diet:
- Prune juice
- Prunes
- Watermelon
- Spinach
- Leafy green vegetables
- Dates
- Raisins
- Broccoli
- Peas
- Fava beans
CALCIUM & THALASSEMIA
Calcium is an essential mineral for building and maintaining strong bones and teeth. Calcium is found in some vegetables such as broccoli and kale, but dairy products such as milk, yogurt, and cheese are much better dietary sources of calcium. Some people either do not like dairy or cannot tolerate a dairy product in their digestive system. For these individuals a good source of calcium can be either calcium fortified orange juice or Tums, an antacid made solely of calcium carbonate.
A diet with inadequate calcium will decrease the storage of calcium in bones, which can become weak and will fracture easily. Weakness of bones is called osteoporosis. The calcium stored in your bones must last you your whole life, so if you have weak bones when you are a young adult it will be difficult to increase their strength as you get older. The peak time for storage is during the teenage years. It is during this time that the bones reach their adult length and strength. It is also during this time that estrogen in young women and testosterone in young men help them develop their bones and make them strong. If there is not enough calcium in their diets, or if there is not enough hormone production, the amount of calcium that is made into bone will be reduced. Since this is the major period of bone development, the bones will be weaker for the rest of a person's life.
Having strong bones is important for all of us, but it is especially important for people with thalassemia. Some of the secondary health problems that occur in children and adolescents with thalassemia affect bone formation. If thalassemia major is not treated with proper blood transfusions, there is so much activity in the bone marrow that bones will become thin and will fracture spontaneously. With adequate transfusion this is not a problem, but with transfusions come other problems; namely, iron overload. If an inadequate amount of Desferal is used and iron builds up in the body, the iron deposition can affect some of the organs that help the body build up strong bones. The major problem that interferes with strong bones is hypogonadism. Iron deposits in the testis in young men and in the ovaries in young women. This iron deposition can cause early menopause in young women in their twenties and can require hormone replacement therapy in both men and women. Without estrogen and testosterone, bones will not form normally and later in life the bones will be susceptible to disease. With replacement of estrogen or testosterone and adequate amounts of calcium, this problem can be prevented. Other problems of calcium metabolism can occur when the thyroid gland is affected by iron overload, and particularly when the parathyroid is damaged by iron.
The major problems can be delayed or prevented by the adequate use of Desferal to prevent damage to the ovaries and testes by iron. In addition, everyone, including children and young adults with either transfusion dependent or non-transfusion dependent thalassemia, should have an adequate intake of calcium, either by eating foods high in calcium or by taking calcium supplements. Exercise in moderate amounts also increases bone strength. It is hard to determine how much calcium is in your diet without knowing how much calcium is contained in foods. At an annual comprehensive clinic visit, each patient can visit a nutritionist to help him or her determine whether enough calcium is coming from the diet. Most people need about 1.5 grams of calcium daily to build strong bones. Children need less: about 1 gram per day. Adolescents need more during this time of increased bone growth: 1.5 to 2 grams per day. Adults need about 1.5 grams per day. These levels of calcium can be achieved by eating foods high in calcium:
High calcium foods (one serving = 400 mg or 0.400 g of calcium):
- One cup of milk
- Yogurt
- Milk based pudding or custard
- 6 sardines with bones
Medium calcium foods (one serving = 125 mg or 0.125 g of calcium):
- One cup tofu
- One cup of beans* or peas
- One cup broccoli, kale, mustard greens*
- One half cup of bok choy or turnip greens*
- One half cup cottage cheese, frozen yogurt, cream soup, or ice cream
- One quarter cup almonds
- 2 ounces canned fish with bones
Remember that if you are on a low-iron diet, try to find alternate sources of calcium, as these (*) tend to be high in iron as well.
Many foods are fortified with calcium: orange juice, breads, soy milk. Look on the labels for both the iron content (avoid iron) and the calcium content of prepared foods. Also important is vitamin C for calcium absorption. If you think about calcium and how important it is for your health, you can easily increase the calcium you receive everyday.
THE VITAMIN C / FERRITIN / IRON CONNECTION
Vitamin C (ascorbic acid) is an essential chemical our body needs to function normally. It is necessary for the body to make connective tissue. It is also essential for the absorption of iron from our foods and plays a role in iron metabolism. Deficiency of ascorbic acid leads to scurvy, which is characterized by easy bruising, mucous membrane bleeding and anemia.
It has been known since the 1960's that vitamin C is intimately involved in iron metabolism when it was noted that when given to treat scurvy, vitamin C increased serum iron levels. In 1962, desferrioxamine (Desferal) began to be used to treat iron overload in thalassemic children in Great Britain. Not long after Desferal was introduced, it was found that vitamin C could double the amount of iron removed during its administration. By 1979 optimum doses of Desferal and vitamin C were still not known. During trials it was discovered that the administration of intramuscular desferrioxamine with daily doses of vitamin C (500 mg per day) was followed by a decrease in cardiac function. Function was returned to normal when the vitamin C was discontinued. Since these trials, lower doses of vitamin C (100 to 250 mg) have been given to individuals who use Desferal, and it has been recommended that the vitamin C be given after Desferal administration has begun.
The above experience and knowledge lead to the rational use of vitamin C during chelation therapy. When Desferal is given in low doses, such as with daily intramuscular injections, high doses of vitamin C makes available more iron from the tissues than the medication can chelate. There has been no cardiac dysfunction reported when vitamin C and Desferal are used appropriately. Vitamin C should never be taken in large doses by individuals who have large total body iron burden.
In the past there has been speculation that ascorbic acid administration could lead to a redistribution of iron from the spleen (the reticuloendothelial cells) to the liver (parenchymal cells). This has not been substantiated by studies in humans, though it may occur in some animals during treatment for ascorbic acid deficiency (guinea pigs).
Ferritin is found in most cells in the body and in the serum. Its function in serum is not known. It is a large complex molecule that sequesters iron. It has 24 protein subunits of two types. These subunits form a structure with a hollow cavity that can sequester 4500 atoms of iron. The iron can enter and exit the ferritin cavity and is part of the metabolic pool of reactive metals in the cell. Iron is necessary for enzyme function and in the mitochondria. The ferritin complexes are continually being recycled within the cell.
Lyosomes are organelles within the cell that sequester and detoxify cellular material that could damage the cell. Ferritin complexes combine together to form even larger complexes that are engulfed by the lyosomes. Once in the lyosomes, the ferritin is converted to hemosiderin, a stable and non-reactive mixture of iron, protein and lipid. The iron is in a non-reactive state and not readily available to the cell. Ascorbic acid decreases the migration of ferritin complexes to the lyosomes, thus directly increasing the amount of ferritin-sequestered iron in the cell and indirectly the reactive iron, since iron can then move out of the ferritin molecule.
Some tissues such as myocardium in the heart have a limited ability to make ferritin. Therefore it has less ability to sequester any free iron released into the body to prevent it from depositing in and damaging the heart. Since vitamin C increases the amount of iron circulating through the body, the myocardium's lack of ferritin makes it extra vulnerable to iron damage. This is the probable mechanism of vitamin C-induced cardiomyopathy.
By increasing the pool of metabolically active iron in the cell, vitamin C increases the pool of iron available for chelation by Desferal. However, too much free iron can cause heart and other problems; thus moderate doses of vitamin taken shortly after starting Desferal infusions will provide optimal iron removal. People who are heavily iron overloaded should not ingest foods such as citrus and some vitamins in large quantities that would give them, for example, a gram (1000 mg) of ascorbic acid a day.
VITAMIN D & OSTEOPOROSIS
Vitamin D is an essential part of our diet from infancy through adulthood. It is metabolized in the liver and kidneys to 1,25-dihydroxyvitamin D, which is the active form of the vitamin. This vitamin has a major role in the absorption and metabolism of calcium. Of course, calcium intake must be maintained for vitamin D to be an effective part of your diet, and there are other factors that are necessary for the growth and preservation of bone.
Vitamin D can be obtained in the diet and is plentiful in dairy products (through fortification), eggs, and fish. Most dietary vitamin D in developed countries comes in the form of fortification of infant formulas, dairy products, cereals, and other fortified foods and vitamin supplements. Exposure of the skin to sunlight also converts a cholesterol compound to vitamin D. There is little standardization for fortification of foods and it is difficult to quantify the amount of vitamin D conversion in the skin, so assessment of dietary vitamin D intake is generally inaccurate. A vitamin D metabolite, 25-hydroxyvitamin D, can be measured in the serum which gives and estimate of the stores of vitamin D in the body and indirectly the amount of vitamin D ingested in the diet.
In the absence of vitamin D severe bone disease, rickets and osteomalacia, can occur but is unusual, except in exclusively breast fed babies in the northern latitudes during the winter months. Much more common is an inadequate amount of vitamin D in the diet. This is particularly common in older individuals who do not drink or eat vitamin D fortified beverages and foods.
In the past, 200 IU of vitamin D was recommended daily for adults. The current daily recommendations are: 200 IU for individuals 19 to 50 years old, 400 IU for individuals 51 to 70 years old, and 600 IU for individuals over 71 years old. Under some conditions these amounts are inadequate. In one study, 700 to 800 IU were necessary to preserve bone density in older individuals.
For individuals who have thalassemia major standard recommendations may not be adequate. A Greek study revealed that individuals who had transfusion dependent thalassemia and who were using desferoxamine for iron overload (these subjects had average serum ferritins greater than 3000 ng/ml) had low levels of vitamin D metabolites. It should be noted that it would appear that these patients were heavily iron overloaded and may have had decreased vitamin D metabolism secondary to compromised liver function.
Osteoporosis is common in thalassemia major and can be modified by an adequate intake of calcium, vitamin D, and in hypogonadism hormone replacement. Individuals who have osteoporosis may require much higher doses of vitamin D to maintain or increase bone density, 800 to 1000 IU per day has been recommended by some experts. An Italian study of bone density in patients with thalassemia showed that only the most severe phenotype (bo/bo) had a decrease in bone density. However, a large daily intake of calcium and vitamin D could lead to hypercalciuria and hypercalcemia; supplementation at higher than recommended doses requires careful monitoring.
All individuals who have thalassemia major should be monitored with bone density studies, serum 25-hydroxyvitamin D levels, parathyroid hormone levels, and evaluation for the development of hypogonadism. In some instances an assessment of bone turnover may be helpful.
If you want more information about your diet, call your health care provider or a nutritionist for a consultation.
This nutritional information contained in this section was partially obtained from www.thalassemia.com at the Northern California Comprehensive Thalassemia Center. For more information about Thalassemia and the treatment options available, please visit their web site. It has a great deal of vital information available to individuals having to deal with this disorder.
NOTIFY YOUR MIDWIFE OR HEALTH CARE PRACTITIONER IF...
Call for an appointment with your health care provider if symptoms develop that are suggestive of thalassemia.
Call your health care provider if symptoms develop after treatment.
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