What Is Thalassemia? Types, Causes & Complete Overview

If you've just been told you or your child has thalassemia — or that you're a carrier — you probably have more questions than answers right now. That's normal. Thalassemia is a lifelong condition, but it's also one of the most well-understood inherited blood disorders in medicine, and most people who have it go on to live full lives with the right care and support.

This guide is meant to be the starting point: a clear overview of what thalassemia is, why it happens, and what the different types mean. We'll link out to deeper posts on diagnosis, treatment, and daily life as they're published, so think of this as your home base.

What Is Thalassemia?

Thalassemia is an inherited blood disorder that affects how your body makes hemoglobin — the protein inside red blood cells that carries oxygen around your body. If you have thalassemia, your body doesn't produce enough normal hemoglobin, which means your red blood cells can't do their job as well, and you end up with fewer healthy red blood cells overall. This is a form of anemia, and depending on the type and severity, it can range from something you'd barely notice to a condition that needs lifelong medical care.

It's worth pausing on one distinction that trips a lot of people up: thalassemia is not the same as the anemia caused by low iron or poor diet. Iron-deficiency anemia happens because your body doesn't have enough iron to make hemoglobin. Thalassemia happens because of a genetic change that affects how hemoglobin is built, regardless of how much iron you have. This matters clinically too — taking iron supplements for thalassemia-related anemia, without a doctor's guidance, can actually cause harm rather than help, since iron overload is already a risk for many people with thalassemia. If you're not sure which one you're dealing with, that's a conversation for your doctor, not a guess based on symptoms alone.

What Causes Thalassemia?

The genetics — how it's passed down

Thalassemia is inherited, meaning it's passed from parent to child through genes. Hemoglobin is built from two types of protein chains, alpha and beta, and thalassemia happens when a genetic change disrupts the production of one of these chains.

Because it takes specific gene combinations to cause the more serious forms, thalassemia typically requires that both parents pass along an altered gene. If a child inherits just one altered gene, they usually become a carrier (sometimes called having "thalassemia trait" or "thalassemia minor") — generally with mild or no symptoms, but able to pass the gene to their own children. If a child inherits altered genes from both parents, the condition is usually more serious. <cite index="5-1">For beta thalassemia specifically, each child of two carrier parents has a 25% chance of inheriting two normal genes, a 50% chance of becoming a carrier, and a 25% chance of inheriting the more serious form</cite>. This is exactly why carrier screening before pregnancy matters so much — we'll cover that in a dedicated post.

Why some communities are affected more than others

<cite index="5-1">Thalassemia occurs most often among people of South Asian, Italian, Greek, Middle Eastern, and African descent</cite>, and it's also common throughout Southeast Asia. Researchers believe this pattern exists because carrying a single altered gene historically offered some protection against malaria — which is part of why these gene variants persisted in regions where malaria was widespread. <cite index="18-1">Globally, an estimated 270 million people carry a thalassemia or related hemoglobin gene variant, with somewhere around 80 to 90 million of those being beta thalassemia carriers specifically</cite>. If your family traces back to any of these regions, carrier screening is worth asking your doctor about — even if no one in your family has ever been diagnosed, since many carriers have no symptoms at all.

The Main Types of Thalassemia

Thalassemia isn't one single condition — it's a spectrum, and the terminology can be confusing at first.

Alpha thalassemia vs. beta thalassemia: <cite index="4-1">these are the two main types, and each depends on which part of the hemoglobin protein — alpha globin or beta globin — isn't being made correctly</cite>. Alpha thalassemia tends to be more common in people of Southeast Asian, South Asian, and African descent; beta thalassemia is more strongly associated with Mediterranean, Middle Eastern, and South Asian ancestry, though there's real overlap.

Trait / minor, intermedia, and major: within each type, severity is usually described in these terms:

• Trait (minor): you carry one altered gene. <cite index="5-1">This usually causes only mild anemia symptoms, if any</cite>.
• Intermedia: a moderate form, with anemia that's more noticeable but doesn't always require the same intensive treatment as major forms.
• Major: the most serious form, <cite index="5-1">also known as Cooley's anemia when referring to beta thalassemia major</cite>, which typically requires regular blood transfusions and lifelong monitoring.

On the alpha thalassemia side specifically, the most serious form — where very little or no alpha globin is produced — is called Hb Bart syndrome, which is diagnosed before or at birth and is extremely serious; the milder serious form is hemoglobin H disease, which usually causes moderate to serious symptoms but is compatible with life. We'll go deeper on each of these distinctions, including alpha vs. beta specifically, in an upcoming post.

Common Symptoms

Symptoms vary enormously depending on type and severity — that's part of what makes thalassemia hard to explain in one sentence. <cite index="3-1">Some people have no symptoms at all, while children with more serious forms often start showing signs by around age two</cite>. When symptoms do appear, they can include:

• Fatigue and weakness
• Pale or yellowish skin (jaundice)
• <cite index="3-1">A larger-than-normal spleen or liver, which can cause a swollen abdomen</cite>
• Slow growth in children
• Bone changes, particularly in the face, in more serious untreated cases

We're keeping this list general on purpose — symptoms in children and adults show up differently enough that it deserves its own post, which is coming soon.

How Thalassemia Is Diagnosed

Diagnosis usually starts with routine bloodwork — often a complete blood count (CBC) that turns up unusually small red blood cells (a clue doctors call microcytosis) — followed by more specific tests like hemoglobin electrophoresis, which identifies the different types of hemoglobin in your blood, and sometimes genetic testing to confirm which genes are involved. <cite index="3-1">More serious forms are frequently caught through routine newborn screening</cite>, which is part of why many parents first hear the word "thalassemia" in their baby's first days of life.

We'll walk through exactly what these tests measure and what your results might mean in a dedicated diagnosis post — this section is just the map, not the full territory.

How Thalassemia Is Managed

Management depends heavily on type and severity, and this is genuinely a conversation to have with a hematologist rather than something to self-manage from general information online. In broad strokes, care can include regular monitoring, blood transfusions for more serious forms, treatment to manage the iron overload that transfusions can cause over time, and in some cases, a bone marrow or stem cell transplant. Newer approaches, including gene therapy, are also changing what's possible for some patients.

We'll cover transfusions, iron overload management, and the latest treatment developments — including gene therapy — in their own posts, since each deserves real depth. If you take one thing from this section, let it be this: thalassemia management is highly individual, and your care team is the right source for decisions about your specific situation.

Living With Thalassemia

A diagnosis — for yourself or your child — can feel overwhelming at first. It's worth saying plainly: this is a condition people build full, meaningful lives around, not despite. Community matters here, and so does hearing from people who've actually lived it.

If you want to hear directly from someone managing thalassemia major day to day, Daniella Macolino's story is a good place to start, alongside Robert Mannino's patient profile — both offer a more personal window into what daily life can look like than a clinical overview ever could. We'll also be publishing a dedicated post on the emotional and mental health side of living with a chronic condition, because that part deserves just as much attention as the physical side.

Frequently Asked Questions

Is thalassemia the same as anemia? Not exactly. Thalassemia causes a type of anemia, but "anemia" is a broad term that covers many causes, including iron deficiency, which is a completely different issue with a different treatment approach.

Can thalassemia be cured? For most people, thalassemia is a lifelong condition managed through monitoring and treatment rather than cured. Bone marrow/stem cell transplant can be curative for some patients in specific circumstances, and gene therapy is an emerging option — both are worth discussing with a hematologist to understand if they're relevant to your situation.

Is thalassemia contagious? No. It's a genetic condition passed from parent to child — it can't be transmitted between people through contact, illness, or any other exposure.

Can two carriers have a healthy child? Yes — carrier status doesn't guarantee an affected child. As noted above, when both parents are carriers, there's still a meaningful chance of a child inheriting no altered genes or being a carrier without symptoms. Genetic counseling can walk through the actual odds for your specific situation.

Is thalassemia the same as sickle cell disease? No, though they're often mentioned together. Both are inherited hemoglobin disorders and both are more common in overlapping populations, but they involve different genetic changes and different disease patterns. We'll cover this comparison in more depth in an upcoming post.

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This article is for general educational purposes and isn't a substitute for medical advice. If you have questions about a diagnosis, symptoms, or treatment, please talk to your hematologist or care team.

Sources:

• National Heart, Lung, and Blood Institute (NHLBI), NIH — What Is Thalassemia, Causes, Symptoms
• StatPearls (NCBI Bookshelf) — Thalassemia
• Global Globin Network / PMC — carrier prevalence estimates

Three Simple Suggestions for a Healthy Diet

In the article below, Ellen Fung, PhD, RD of UCSF Benioff Children’s Hospital Oakland and Farah Sultan, RD of McMaster University, share some nutritional information for people with thalassemia.

One of the most common questions we are asked as nutritionists is, “What should I be eating?” In many ways, the diet for individuals with thalassemia is no different than for anyone else: the key is balance. However, the needs for certain nutrients are much higher in thalassemia. Therefore, nutrient density is very important! This means every calorie must count. Rather than worrying about which specific foods are “good” for you or which foods are “bad,” it’s better to focus on choosing a variety of foods that are packed with vitamins, minerals, fiber and other nutrients. Making smart, balanced food choices every day can help you stay healthy.
Here are some strategies you can use:

• Eating Around the Rainbow: Healthy foods we eat come in a variety of colors: kale (green), carrots (orange), beets (red), red cabbage (purple). Fruit loops don’t count here! Each food derives its color from the rich concentration of antioxidants in its skin and flesh. The variety of colors comes from a diverse range of anthocyanins (plant pigments) and antioxidants (for example, carrots and sweet potatoes are orange because of the antioxidant, beta-carotene). By eating a variety of foods of different colors throughout the day (eating around the rainbow), you will be consuming more antioxidants, substances which are important for reducing the damage that can be caused by the free iron in your body.

• My Plate: Smaller Portions, More Vegetables and Fruit. If you are not familiar with the “My Plate” campaign from the USDA, you should take a look at it (see below and at www.choosemyplate.gov). This newest guideline for eating healthy is a simple set-up of a small plate which is divided into portions, roughly ¼ for protein, ¼ for grain/carbohydrates and ½ of the plate set aside for fruits & vegetables. If we ate all our meals this way, we would be consuming many more vitamins and minerals in our diet. Think about this the next time you sit down for lunch and dinner.

• Eat Food, not Supplements. The best way to get all of our nutrients is through our food. Most nutrients are best absorbed when they come from our food (e.g. calcium – milk, zinc – chicken) rather than in the form of supplements. Nutrients found within foods are created in such a way to avoid competition for absorption in your body whereas the form of nutrients in some supplements may result in poor absorption. Food also contains much needed fiber as well as other substances (phytochemicals, flavonoids) that are important for your health. When healthy foods are replaced by foods with poor nutrient density (e.g. empty calories) + dietary supplements, you miss out on all of the benefits of food. Not to mention the simple joys of consuming delicious, nutritious foods! However, we must be clear…Individuals with thalassemia may require certain supplements (e.g. vitamin D) in addition to their diet; but supplementation should NOT REPLACE a healthy diet.

Making healthy choices doesn’t have to be complicated — simply begin by making one change in your daily routine, such as making sure to have one colorful vegetable every day. You may just be surprised how simple it can be, and how great you can feel.
Ellen Fung, PhD RD
Associate Research Scientist
UCSF Benioff Children’s Hospital Oakland
Oakland, CA USA
Farah Sultan, RD
Master’s Degree Student, Nutritional Science
McMaster University
Toronto, ON Canada

Developing first comprehensive guidelines for management of sickle cell disease

The National Heart, Lung, and Blood Institute has released the first comprehensive, evidence-based guidelines for management of sickle cell disease from birth to end of life. Sickle cell anemia is the most common form of sickle cell disease, a serious disorder in which the body makes sickle-shaped red blood cells.

 

Shirley Miller with Dr. George Buchanan, Professor of Pediatrics and Internal Medicine, holder of the Children's Cancer Fund Distinguished Chair in Pediatric Oncology & Hematology.

 The National Heart, Lung, and Blood Institute (NHLBI) has released the first comprehensive, evidence-based guidelines for management of sickle cell disease from birth to end of life, based on recommendations developed by a nationwide team of experts co-chaired by a UT Southwestern Medical Center hematologist.

 Appearing today in JAMA, the guidelines are intended for general use by pediatricians, physicians treating adults, hematologists, emergency room personnel, hospitalists, and other health care providers. The new management guidelines consist of more than 500 specific directions for physicians who are caring for patients with sickle cell disease.

"The aim is to improve the care of all people with sickle cell disease, young and old, and to raise awareness among the entire medical profession regarding the need for better care and more research, so that someday everyone with sickle cell disease can receive the best possible care and lead a normal and productive life," said Dr. George Buchanan, Professor of Pediatrics and Internal Medicine.

Although currently most patients are diagnosed at birth and survive until adulthood, many sickle cell disease patients die in their 30s and 40s of acute complications or chronic organ damage. Dr. Buchanan and the team of expert panelists want to alter that statistic through improved and comprehensive treatment.

One survivor who beat those numbers is 58-year-old Shirley Miller, who worked at UT Southwestern with Dr. Buchanan from 2002 to 2010 as a program manager, patient advocate, and outreach coordinator.

"I lived my life in fear because I thought age 30 was it. I wasted a lot of time wondering how the end would happen. My parents never told me my life expectancy; I went to the library and looked it up," said Ms. Miller, who is now helping to launch a comprehensive sickle cell adult program in Charlotte, North Carolina.

Diagnosed at age three, and the only one of five siblings with the disease, she grew up without physical education classes and did not participate in sports. She made friends slowly and was embarrassed when others went through puberty before her. She credits her parents with helping her believe she could make it, and she credits the care she later received as an adult at UT Southwestern.

"Comprehensive care is the key to successful management of sickle cell disease, known as sickle cell disease. Currently, there are not enough physicians who specialize in the care of adults with sickle cell disease, which means that many are seen by primary care physicians or other specialists," said Ms. Miller. "These guidelines will provide physicians with a tool for basic understanding of the disease etiology and possible complications to look for when managing a patient. I attribute my survival to the comprehensive care that I received from this teaching and research university, which is on the cutting edge of so many developments. The knowledge and expertise available here have made all the difference."

The expert panel for the new guidelines is a 12-member team, all known for their experience in diagnosing and treating people with sickle cell disease. Panel members included two pediatric hematologists, four adult hematologists, an obstetrician, a psychiatrist, an emergency department nurse, two blood transfusion specialists, and one family physician. These experts were supported by a large staff of NHLBI leaders and other personnel, including experts in finding and analyzing the available scientific evidence that could help improve the lives of people with sickle cell disease.
Sickle cell disease is the world's most common serious condition due to a single gene mutation. An estimated 70,000 to 100,000 people in the U.S. have sickle cell disease. Of these, about 1,000 receive care annually at UT Southwestern. Dr. Buchanan has led the institutional pediatric and research sickle cell disease programs for 37 years.

More than 2 million Americans carry the sickle cell trait.
"African-Americans are far more likely than Caucasians to have the sickle cell trait, which is not a disease but a carrier state. One has to receive a copy of the abnormal gene from both parents to have the disease," said Dr. Buchanan, who holds the Children's Cancer Fund Distinguished Chair in Pediatric Oncology & Hematology.
"Every state now has mandatory newborn screening for the disease," said Dr. Buchanan, Director of the Barrett Family Center for Pediatric Oncology at UT Southwestern.
Dr. Buchanan was instrumental in ensuring that Texas became the third state to adopt newborn screening in 1983. Approximately 150 infants with sickle cell disease are diagnosed in Texas each year. Nearly one third of them receive their care at Children's Medical Center in Dallas.

When sickle cell disease progresses, it can delay puberty and cause acute and chronic complications, including debilitating pain, life-threatening infections, damage to vital organs, and stroke. Stem cell transplants offer a potential cure; however, the high cost, lack of suitable donors (ideally the donor is a sibling), and the risk of complications make these transplants relatively infrequent. The newly published comprehensive guidelines recommend better pain control; prevention and treatment of acute and chronic complications; general health maintenance; judicious use of blood transfusions; and teaching patients to manage their disease through behavioral changes.

The committee also strongly advocates for prescribing hydroxyurea, an oral medication taken once daily that has become the standard of care. Hydroxyurea reduces the impact of the disease by improving the anemia, and reducing the risk of pain events and acute chest syndrome. It can also decrease the need for transfusions and hospital admissions.
"These national guidelines are directed not just to hematologists but to all medical practitioners who might encounter sickle cell disease patients, to inform them about hydroxyurea and how to best offer general medical care to them," Dr. Buchanan said. "We have a lot of work to do to educate physicians."

September is National Sickle Cell Awareness Month, and the guidelines will be discussed and disseminated at professional conferences, as well as being available on the NHLBI website and in JAMA, the journal of the American Medical Association.
According to NHLBI, sickle cell anemia is the most common form of sickle cell disease, a serious disorder in which the body makes sickle-shaped red blood cells. "Sickle-shaped" means that the red blood cells are shaped like a crescent. Normal red blood cells are disc-shaped and look like doughnuts without holes in the center, moving easily through blood vessels. Red blood cells contain an iron-rich protein called hemoglobin, which carries oxygen from the lungs to the rest of the body. Sickle cells contain abnormal hemoglobin called sickle hemoglobin or hemoglobin S. They tend to block blood flow in the blood vessels of the limbs and organs, causing pain, organ damage, and increased risk for infection. In the U.S., the disease occurs in about one out of every 500 African-American births and in more than one out of every 36,000 Hispanic-American births.

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The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.

New Guidelines for Sickle Cell Disease

An expert panel has issued new guidelines for managing sickle cell disease, stressing the use of the drug hydroxyurea and transfusions for many with the genetic disorder.

By Kathleen Doheny
HealthDay Reporter

 “This is a major step forward to try to put together all of the evidence and try to highlight what is most important,” said Dr. Barbara Yawn, professor of family and community health at Olmsted Medical Center in Rochester, Minn. Yawn was also co-chair of the panel convened by the U.S. National Heart, Lung, and Blood Institute to develop the new guidelines.

As many as 100,000 Americans have sickle cell disease, according to background information with the guidelines. In sickle cell disease, the body makes sickle-shaped or crescent-shaped red blood cells. Normal red blood cells are disc-shaped, like a doughnut without holes, allowing the cells to move easily through blood vessels.

Sickle cells are stiff and sticky and tend to block blood flow, leading to organ damage, pain and increased risk of infection and strokes, among other problems. Black people are more commonly affected than other people.

The expert panel reviewed more than 12,000 scientific articles and sifted through the evidence to issue the new blueprint for care. The new guidelines are published Sept. 10 in the Journal of the American Medical Association.

One of the new recommendations is to give children oral penicillin daily until age 5. This is a preventive measure, aiming to reduce the risk of pneumonia and other infections.

“That has been the standard for a while now,” Yawn said. “Now we are saying ‘This is an absolute necessity.'”

In addition, everyone with sickle cell disease should be vaccinated against pneumonia, according to the guidelines. “The children need pneumococcal vaccine as early as they can possibly get it, around six weeks of age,” Yawn said.

Children from ages 2 to 16 should have an annual exam known as a transcranial Doppler, which measures blood flow in the brain, the guidelines explain. If it’s abnormal, long-term transfusion therapy to prevent stroke is recommended. 

When acute complications occur, opioids (also known as narcotics) are suggested to treat the pain linked with blood flow blockage. A method of encouraging deep breathing — incentive spirometry — is also advised for those hospitalized with a blood flow crisis.

If adults have three or more severe blood flow crises in a year, treatment with the drug hydroxyurea is recommended. The drug works in sickle cell by helping to prevent the formation of sickle-shaped red blood cells. Hydroxyurea can be used in infants, children and teens, whether or not they currently have symptoms, according to the guidelines.

One difficulty in developing the guidelines, Yawn said, is that there is “not enough research to answer all the questions.”

People with sickle cell disease are living longer, she said. A generation ago, many with sickle cell disease only survived until their 20s or 30s. “We know there are more living into their 40s, 50s and 60s,” she said.

Dr. Michael DeBaun, professor of pediatrics and medicine at the Vanderbilt University School of Medicine, said, “These are really strong recommendations.”

DeBaun wrote an editorial to accompany the guideline report. “This should now be a road map of how your child should be cared for,” he said.

The information also applies for adults with sickle cell disease, said DeBaun, who is also director of the Vanderbilt–Meharry Sickle Cell Disease Center of Excellence.

He advises patients and parents to use the new guidelines to have a dialogue with the doctors providing care. “We expect these recommendations to change over time as more evidence becomes available,” DeBaun said.

In his own recent study, published in August in the New England Journal of Medicine, DeBaun and his colleagues reported that monthly blood transfusions appear to reduce the risk of strokes in children with sickle cell anemia, the most common form of sickle cell disease.

More information

To learn more about sickle cell disease, visit the U.S. Centers for Disease Control and Prevention.

6 causes of anemia during pregnancy

Gestational anemia or anemia during pregnancy is one condition that can affect a woman at any time during her pregnancy.

While planning your pregnancy, you need to make sure that your health is at its optimum. This includes your blood count, fitness and management of various lifestyle related ailments. All this will ensure a smooth pregnancy and good health of both the mother and the child growing inside the womb. However, those nine months of pregnancy aren’t predictable, and health complications can arise at any time. Gestational anemia or anemia during pregnancy is one such condition that can affect a woman at any time during her pregnancy.

Here are a few causes that could lead to the same:

Deficiency of iron
Iron deficiency during pregnancy is a common cause of gestational anemia. This happens when the body is unable to produce enough iron to produce adequate hemoglobin. Hemoglobin is a protein that is present in the red blood cells. During pregnancy the blood supply in the body almost doubles up to meet the requirements of the mother and that of the growing baby. The hemoglobin in the blood is responsible for nutrient and oxygen exchange between a mother and the baby. It is also responsible for oxygen circulation in the mother to restore health during pregnancy. During pregnancy the iron requirement for a woman increases and one might need around 30 to 38 mg of iron either through dietary sources or by having iron supplements regularly. Here are reasons why you need to be regular with iron medications during pregnancy.

Deficiency of folic acid
Everyone knows the importance of folic acid during pregnancy. It is a type of B vitamin that helps produce new cells including healthy red blood cells. Therefore, during pregnancy a woman needs more folate. It is recommended that women take at least 400 mg of folate during pregnancy to avoid birth defects in babies. Folate or folic acid deficiency can lead to less production of red blood cells that could hamper oxygen and nutrient supply to the fetus and result in severe birth defects like neural tube abnormalities or spina bifida and lead to low birth weight of the baby. This kind of anemia can be easily corrected by taking folic acid pills or through proper diet management. Here are reasons why you need folic acid during pregnancy. 

Vitamin B 12 deficiency
Vitamin B 12 is an important vitamin for pregnant women that plays a major role in producing healthy red blood cells. Lack of Vitamin B 12 in the diet could give rise to the gestational anemia that could contribute to birth defects, such as neural tube abnormalities, and lead to preterm labor. Women who don’t eat meat, poultry, dairy products, and eggs have a greater risk of developing vitamin B12 deficiency. Here are other seven diet essentials you should take during pregnancy.  

Having twins
Mothers who are carrying twins or triplets need special care to meet the demands of their growing babies. Improper diet and ignorance of medications can lead to various health complications and gestational anemia could be one of them. Women with twins or triplets are always at risk of developing complications during pregnancy.

Improper diet
Gestational anemia as mentioned above could be easily avoided with proper diet management and being regular with medications. Irregularities in diet especially failing to get enough iron, folate and vitamin B 12 could lead to the gestational anemia in women. Know more about the causes, symptoms and treatment of anemia during pregnancy.

Being anemic before conception
If you were anemic or had lower hemoglobin count prior to conception you could be at a risk of developing gestational anemia. Even with adequate hemoglobin count during the start of pregnancy it is possible to suffer from gestational anemia. This happens due to altered body mechanism and the various hormonal changes. It is imperative to check with your doctor about medications and management of anemia during pregnancy, especially if you had suffered from the same before.

Educational Webcast on Beta-thalassemia

An online seminar lead by Prominent hematology expert, Ellis Neufeld, M.D., Ph.D.

Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases,hosted an educational webcast seminar on beta-thalassemia with Ellis Neufeld, M.D., Ph.D on 17.10.2014. Acceleron and its collaboration partner, Celgene, are conducting phase 2 clinical trials of sotatercept and luspatercept in patients with beta-thalassemia, MDS, and end-stage renal disease with mineral and bone disorder.

Dr. Neufeld currently serves as Associate Chief of the Hematology/Oncology Division and Co-Chief of the Clinical Research Center at Boston Children’s Hospital, Director of the Boston Hemophilia Center, and is the Egan Family Foundation Professor of Pediatrics at Harvard Medical School.

Dr. Neufeld provided an overview of beta-thalassemia including the numerous clinical complications of the disease, current treatment and a review of the recently presented data from the sotatercept and luspatercept phase 2 studies in beta-thalassemia.

 To access the recorded webcast, please visit the "Events & Presentations" page in the Investors & Media section on the Company's website (http://investor.acceleronpharma.com/events.cfm).

Acetate supplements speed up red blood cell production, anemia research shows

UT Southwestern Medical Center researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

 Currently, the hormone erythropoietin is administered to treat anemia, but this treatment carries with it side effects such as hypertension and thrombosis (blood clotting). The new research, which was performed in mice, suggests that acetate supplements could eventually be a suitable supplement or possibly even an alternative to administration of erythropoietin.

"Using rational interventions based on the mechanistic insights gleaned from our current studies, we may be able to treat acutely or chronically anemic patients with acetate supplements and thereby reduce the need for blood transfusions or erythropoietin therapy," said Dr. Joseph Garcia, Associate Professor of Internal Medicine at UT Southwestern, staff physician-scientist at the VA North Texas Health Care System, and senior author of the study, published in Nature Medicine.

Anemia is the most common blood disorder, affecting some 3.5 million people, including children and women of child-bearing age, as well as many elderly persons. It can have a significant impact on quality of life, leading to fatigue, weakness, and decreased immune function. People who are anemic produce insufficient red blood cells, which deliver oxygen to tissues throughout the body.

UT Southwestern researchers began their studies by identifying a critical pathway that controls the production of red blood cells in conditions of stress, such as low oxygen. Using genetically modified mice, researchers observed that low oxygen, a state known as hypoxia, stimulates the production of acetate.

Acetate, in turn, activates a molecular pathway that ultimately results in the production of red blood cells, or erythropoiesis, by triggering the production of the protein that stimulates this process, called erythropoietin.

"Our study shows that acetate functions as a biochemical 'flare,' linking changes in cell metabolism that occur during hypoxia with the activation of a selective stress signaling pathway," Dr. Garcia said.

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Gene mutation discovered in blood disorder aplastic anemia

An international team of scientists has identified a gene mutation that causes aplastic anemia, a serious blood disorder in which the bone marrow fails to produce normal amounts of blood cells. Studying a family in which three generations had blood disorders, the researchers discovered a defect in a gene that regulates telomeres, chromosomal structures with crucial roles in normal cell function.

 "Identifying this causal defect may help suggest future molecular-based treatments that bypass the gene defect and restore blood cell production," said study co-leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia (CHOP).

Hakonarson and CHOP colleagues collaborated with Australian scientists on the study, published online Sept. 9 in the journal Blood.

"We're thrilled by this discovery which has advanced our understanding of certain gene mutations and the causal relationship to specific diseases," said study co-leader Tracy Bryan, Ph.D., Unit Head of the Cell Biology Unit at the Children's Medical Research Institute in Westmead, New South Wales, Australia.
The research team studied an Australian family with aplastic anemia and other blood disorders, including leukemia. Hakonarson and lead analyst Yiran Guo, Ph.D., along with genomics experts from BGI-Shenzhen, performed whole-exome sequencing on DNA from the families and identified an inherited mutation on the ACD gene, which codes for the telomere-binding protein TPP1.

Telomeres, complex structures made of DNA and protein, are located on the end of chromosomes, where they protect the chromosomes' stability. They are sometimes compared to plastic tips at the end of shoelaces that prevent the laces from fraying.

Telomeres shorten after each cell division, and gradually lose their protective function. Aging cells, with their shortened telomeres, become progressively more vulnerable to DNA damage and cell death. Separately from the aging process, certain inherited and acquired disorders may shorten telomeres and injure rapidly dividing blood-forming cells produced in bone marrow. This leads to bone marrow failure, one example of which is aplastic anemia.

Bryan's team investigated the function of the ACD gene. They determined that the mutation shortened telomeres and interrupted the ability of telomeres to attract the enzyme telomerase, which counteracts telomere shortening and thus protects cells.

In the current study, the researchers showed that the mutation in ACD alters the telomere-binding protein TPP1, disrupting the interactions between telomere and telomerase. Without access to telomerase to help maintain telomeres, blood cells lose their structural integrity and die, resulting in bone marrow failure and aplastic anemia.
Nine other genes were previously found to play a role in bone marrow failure disorders. The current study adds ACD to the list, the first time the gene has been shown to have a disease-causing role.
"This improved understanding of the underlying molecular mechanisms may suggest new approaches to treating disorders such as aplastic anemia," said Hakonarson. "For instance, investigators may identify other avenues for recruiting telomerase to telomeres to restore its protective function."

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The above story is based on materials provided by Children's Hospital of Philadelphia. Note: Materials may be edited for content and length.

Adults stop anti-rejection drugs after partial stem-cell transplant reverses sickle cell disease

NIH trial success suggests a new treatment option for older, sicker patients

Half of patients in a trial have safely stopped immunosuppressant medication following a modified blood stem-cell transplant for severe sickle cell disease, according to a study in the July 1 issue of the Journal of the American Medical Association. The trial was conducted at the National Institutes of Health’s Clinical Center in Bethesda, Maryland, by researchers from NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute.
The transplant done in the study reversed sickle cell disease in nearly all the patients. Despite having both donor stem-cells and their own cells in their blood, the patients stopped the immunosuppressant medication without experiencing rejection or graft-versus-host disease, in which donor cells attack the recipient. Both are common, serious side effects of transplants.
"Typically, stem-cell recipients must take immunosuppressants all their lives,” said Matthew Hsieh, M.D., lead author on the paper and staff clinician at NIH. “That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen.”
In sickle cell disease (SCD) sickle-shaped cells block blood flow. It can cause severe pain, organ damage and stroke. The only cure is a blood stem-cell, or bone marrow, transplant. The partial transplant performed in the study is much less toxic than the standard “full” transplant, which uses high doses of chemotherapy to kill all of the patient’s marrow before replacing it with donor marrow. Several patients in the study had less than half of their marrow replaced.
Immunosuppressant medication reduces immune system strength and can cause serious side effects such as infection and joint swelling. In this study, 15 of 30 adults stopped taking the medication under careful supervision one year after transplant and still had not experienced rejection or graft-versus-host disease at a median follow up of 3.4 years.
“Side effects caused by immunosuppressants can endanger patients already weakened by years of organ damage from sickle cell disease,” said John F. Tisdale, M.D., the paper’s senior author and a senior investigator at NIH. “Not having to permanently rely on this medication, along with use of the relatively less-toxic partial stem-cell transplant, means that even older patients and those with severe sickle cell disease may be able to reverse their condition.”
“One of the most debilitating effects of sickle cell disease is the often relentless pain,” added Dr. Hsieh. “Following the transplant, we saw a significant decrease in hospitalizations and narcotics to control that pain.”
The partial transplant used donor stem-cells from healthy siblings. It effectively reversed SCD in 26 of 30 patients and allowed them to achieve stable mixed donor chimerism, a condition in which a person has two genetically distinct cell types in the blood. The study includes patients from an NIH study reported in 2009, in which partial stem-cell transplants reversed SCD in 9 of 10 people.
In the United States, more than 90,000 people have SCD, a genetic disorder found mainly in people of African ancestry. Worldwide, millions of people have the disease.
“The devastating complications associated with sickle cell disease can deeply affect quality of life, ability to work and long-term well-being,” said NIDDK Director Griffin P. Rodgers, M.D., a co-author on the paper. “This study represents an important advance in our efforts to make a potentially transformative treatment available to a wider range of people, especially those who could not tolerate a standard stem-cell transplant or long-term use of immunosuppressants.”
People with sickle cell disease interested in joining NIH blood stem-cell transplant studies may call 1-800-411-1222 or visit http://www.clinicaltrials.gov for more information.
The Sidney Kimmel Cancer Center at Johns Hopkins Medical Institute provided input into trial design.

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Part of the NIH, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI news releases and other materials are available online at: http://www.nhlbi.nih.gov.
The NIDDK, part of the NIH, conducts and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The institute's research interests include: diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic and hematologic diseases. For more information, visit http://www.niddk.nih.gov.
The NIH Clinical Center (CC) provided clinical laboratory and transfusion medicine support and care for stem-cell donors and recipients. The CC is the clinical research hospital for the NIH. Through clinical research, physician-investigators translate laboratory discoveries into better treatments, therapies and interventions to improve the nation's health. For more information, visit http://clinicalcenter.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

No More Transfusions,Your Child Can Live Without Beta Thalassemia Major

Following is some interesting information we have came across recently. It's solely your decision whether to get in touch with them or not.

Your child can live without beta thalassemia major with no more transfusions,thanks to Bone Marrow Transplant(BMT),  a 30 years reliable technique applied to more than 3,000 patients worldwide. 89% of low risk children are successfully cured.

Ask the free advice to Dr. Pietro Sodani,our co-founder and scientific coordinator, hematologist, BMT expert and inventor of BMT from haploidentical mother to child with thalassemia using protocol 30,who has done in the last 15 years more than 400 BMT in thalassemia with Prof. Lucarelli,the inventor of BMT from matching sibling and the worldwide authority.
 
With Bone Marrow Transplant (BMT) your child can become beta thalassemia major free (no more transfusions). Each child is different and has his own health conditions.
Dr. Pietro Sodani (co-founder and scientific coordinator. Hematologist, BMT expert and inventor of BMT from haploidentical mother to child with thalassemia using protocol 30,who has done in the last 15 years more than 400 BMT in thalassemia with Prof. Lucarelli,the inventor of BMT from matching sibling and the worldwide authority) gives you via email his free professional advice to tell how your child can have a BMT to be thalassemia free,and what the results might be.

 Go to www.curethalassemia.org  for more details

Medical leap gives hope to blood disorder sufferers

Gene therapy for the blood disorder beta-thalassemia will be carried out in Thailand for the first time by the end of this year.

A team of doctors at Ramathibodi Hospital is studying the gene therapy technology alongside experts in Paris under a collaboration programme between the Mahidol University led by Prof Suthat Fucharoen and French-American researcher Philippe Leboulch of Harvard Medical School and the University of Paris.
The Thai doctors expect to return to Thailand to conduct a trial around December, said Dr Suradej Hongeng, of Ramathibodi Hospital's department of pediatrics.
The collaboration came about after the world's first successful treatment of beta-thalassemia with gene therapy.
A 21-year-old Frenchman treated with the therapy in 2007 now no longer has the need for blood transfusions. He previously had required transfusions every month since birth.
The successful treatment was published in the journal Nature last September.
Beta-thalassemia is caused when a patient cannot produce enough of the beta-globin component of haemoglobin, the protein used by red blood cells to carry oxygen around the body. This can cause life-threatening anaemia, leading to severe damage of the body's major organs.
Gene therapy is generally the insertion, alteration or removal of genes within a patient's cells and biological tissues to treat disease.
"This success justifies the hopes placed in the use of gene therapy to treat blood diseases," said Dr Suradej, a haematology specialist.
"It is also the first time an effective technology has been developed to improve the quality of life for people with thalassemia."
An estimated 20 million Thais are carriers of thalassemia. It is one of the world's most common genetic disorders, putting an enormous financial strain on Thailand and countries located in the "Thalassemia Belt", which stretches from the Mediterranean through the Middle East and Central Asia to Southeast Asia.
About three in 800 children born in Thailand are affected by the severest form of the disorder, beta-thalassemia, requiring regular blood transfusions.
However, blood transfusions carry the risk of contracting HIV and hepatitis B and C from donors, or iron overloading.
The only known cure for the condition is through a bone marrow transplant.
However, this process is dangerous and it can be very difficult to find a matching bone marrow donor, Dr Suradej said.
He hoped the gene therapy for thalassemia treatment would eliminate the problems posed by bone marrow transplants, as well as lead doctors to adapt the technology to treat the symptoms of beta-thalassemia, such as as neurological problems and muscle disabilities.

Gene Rx May Fight Severe Blood Disorder

But far more research is needed to know whether treatment is safe and effective, researcher cautions

By Steven Reinberg - HealthDay Reporter

Patients suffering from a severe, inherited blood disorder may one day benefit from a new gene therapy and no longer need regular blood transfusions, new research suggests.
However, far more study is needed to determine whether the therapy is safe and effective. So far only one patient has received the experimental treatment, and the researchers have followed him for only three years.
The blood disorder -- beta-thalassemia -- occurs when a crucial blood protein known as beta globin is missing from the red blood cells that carry oxygen. Without beta globin, many of the red blood cells die off, causing severe anemia and eventually death if the person goes untreated.
Beta-thalassemia mostly affects people of Mediterranean, Middle Eastern, Southeast Asian and Chinese descent. Some 100,000 children are born with the disease each year around the world, according to the March of Dimes, and untreated, those with the most severe form usually die in childhood.
In those treated, the excess iron building up from the blood transfusions must be removed with chelating drugs, which can cause unpleasant side effects ranging from joint pain and vomiting to vision and hearing problems.
And even though lifesaving treatments have greatly improved prospects for long-term survival, those with the disorder are at risk of heart failure and other life-threatening complications -- some related to the treatments themselves -- as they age.
Among those struggling with this illness -- and often losing -- was a teenager who volunteered for the gene therapy. Like many others, he needed a matched donor for a stem cell transplant, but none was available, the study noted.
"The patient was 18 years old when we first treated him and [had been] transfused monthly for most of his life," said lead researcher Dr. Philippe Leboulch, a professor of medicine and cell biology at the University of Paris in France.
Transfusions continued until a year after the treatment, Leboulch said. "One year after the treatment he became transfusion-independent," he said. "That has been the case for over two years now."
For the study, Leboulch's team worked on a modified virus and removed all the viral genes. They then replaced those genes with a so-called globin gene. In addition, they added factors so the gene would act only on red blood cells, where the iron-rich protein known as hemoglobin normally carries oxygen throughout the body.
This new "gene" was then injected into the patient, where it went on to repair the damaged globin gene and started producing normal hemoglobin, Leboulch said.
"This is one more example of a gene therapy that starts to show a clinical benefit for patients," he said.
However, Leboulch is cautious. "This is the first patient in the trial. Of course we need to do more patients and see what happens," he said.
Leboulch noted another problem with gene therapy: the inability to control all the effects a new gene will have in the body. The globin gene, for example, appears to link to another gene that is involved in cell growth, causing a mild expansion of blood stem cells in the patient's body. This could account for some therapeutic benefits, but might also be a precursor to cancer, the researchers noted.
"So far there is no sign of any abnormality," Leboulch said.
Dr. Francoise Bernaudin, a clinical hematologist who has followed the patient since early childhood, said it was "wonderful to see that this young man is for now free of transfusions and injections for iron chelation.
"He is happy to have a normal life back, and for the first time has a full-time job as a cook in a main restaurant in Paris," said Bernaudin in a news release on behalf of bluebird bio, developer of the LentiGlobin gene therapy treatment that the researchers are using. The trials are sponsored by the Cambridge, Mass.-based bluebird bio.
The report is published in the Sept. 16 issue of Nature.
Based on their initial success with gene therapy, Leboulch's group plans to treat another two patients. If they also respond well, they will enroll "a larger cohort" of patients, he said.
In addition, the researchers plan to treat patients who have sickle cell disease with the gene therapy as well, Leboulch said. The same technique can be used for both diseases, he said.
Leboulch concedes that the treatment is very expensive. But he hopes that if it becomes widely used, the price will drop, eventually costing less than a lifetime of monthly transfusions and chelating drugs.
Dr. Mustafa Tekin, an associate professor at the John P. Hussman Institute for Human Genomics at the University of Miami Miller School of Medicine, said that "gene therapy has been long awaited for thalassemia."
"This is the first example of a successful gene therapy for beta-thalassemia," he said. "This brings great hope for patients for the final cure for the disorder."
However, there are possibilities of adverse effects, Tekin said. He joined the researchers in cautioning that treatment to date has been limited to just one patient.
Tekin said that the gene that absorbed the therapeutic gene is associated with certain cancers, such as leukemia. While the patient does not have signs of the cancer, it is important "to follow this patient for the long-term for signs of leukemia," he said.
More trials and patients are needed to really assess the effects and side effects of the treatment, Tekin said. Whether it will treat other forms of thalassemia isn't known, he added.
"One patient is important and a significant achievement, but you still need to see more patients to make sure that it works for many patients and also that it works safely," he said.
 

Beta-Thalassemia: Gene Therapy Breakthrough

Italian scientists pioneering a new gene transfer treatment for the blood disorder β-thalassemia have successfully completed preclinical trials, claiming they can correct the lack of beta-globin (β-globin) in patients' blood cells which causes the disease. The research, published in EMBO Molecular Medicine, reveals how gene therapy may represent a safe alternative to current cures that are limited to a minority of patients.

The disorder β-thalassemia, also known as Cooley's anemia, is caused when a patient cannot produce enough of the β-globin component of haemoglobin, the protein used by red blood cells to carry oxygen around the body. The lack of β-globin causes life threatening anemia, leading to severe damage of the body's major organs. The condition is most commonly found in Mediterranean, Middle Eastern and Asian populations.

"Currently treatments are limited to lifelong regular blood transfusions, and iron chelation to prevent fatal iron overload. The alternative is bone marrow transplantation, an option open to less than 25% of patients," said Dr Giuliana Ferrari from the San Raffaele Telethon Institute for Gene Therapy in Milan. "Our research has focused on gene therapy: by transplanting genetically corrected stem cells we can restore haemoglobin production and overcome the disorder."

Diseases of the blood are good targets for gene therapy because it is possible to harvest stem cells from the patient's bone marrow. The team developed a tool to deliver the correct gene for ß-globin into these harvested cells, a viral vector they called GLOBE.

The cells can then be genetically modified with GLOBE to restore hemoglobin production before being re-administered back into the patient via intravenous injections. The important focus of this work was not only to show that GLOBE can restore haemoglobin production in human cells, but that this genetic transfer-based approach does not impair the biological features of the cells and is not associated with any intrinsic risk for the human genome.

This research is not only crucial for developing a cure for one disease, but as Dr David Williams from the Harvard Medical School says, it may advance the entire discipline of gene therapy research

"This work represents the kind of translational studies that are required to move human investigations forward but are often difficult to fund and publish," said Williams. "Considering the inherent difficulties accompanying human research, studies like those reported in EMBO Molecular Medicine are extremely important for moving the field forward." As the Milan based team can now correct the defective production of beta-globin in patients' blood cells the next step will be to place the corrected cells back into the patient, a step which has already proven successful in mice.

Successful gene therapies are the results of very long studies and our research represents the most comprehensive pre-clinical analysis ever performed on cells derived from thalassemic patients" concluded Ferrari. "We believe this study paves the way forward for the clinical use of stem cells genetically corrected using the GLOBE vector."

Source:
Ben Norman
Wiley-Blackwell

Study Looks at Pregnancy in Thalassemia

A recent study published in Haematologica (Vol. 95, Issue 3) examined pregnancy in women with thalassemia.
Entitled "Pregnancy and Beta-thalassemia: an Italian multicenter experience," the paper examined 58 pregnancies among 47 women with thalassemia major and 17 pregnancies in women with thalassemia intermedia at four centers in Italy. The study reports that conception was spontaneous in all of those with thalassemia intermedia; among those with thalassemia major, gonadotrophin-induced ovulation was required in 33 of the women.
According to the study, 91% of the pregnancies among alassemia major patients resulted in live births (45 single births, 5 sets of twins, one set of triplets). The authors also report that no secondary complications of iron overload developed or worsened during pregnancy. There was a higher prevalence of pre-term births (32.8%), but the authors state that this was primarily related to multiple pregnancies and precautionary measures. Women with thalassemia intermedia who had never been transfused or who had only minimal transfusion prior to pregnancy were found to be at risk of severe alloimmune anemia if transfusions were required during pregnancy. (Decreased hemoglobin levels necessitated transfusion in 11 of the 17 thalassemia intermedia pregnancies.) Of the 17 pregnancies in thalassemia intermedia known to the researchers, 15 resulted in live births.
The authors also state that "cardiac function was not impaired during pregnancy." One patient did experience worsening of T2* scores, but the authors suggest that this was due to the timing of the second MRI reading; as it was taken one month after delivery, the patient was still off chelation. The authors also stated that "it is strongly recommended that thalassemic women wishing to become pregnant undergo a complete evaluation of organ iron overload, including MRI T2* and SQUID, prior to pregnancy." (In the United States, Ferriscan/R2 readings are often used for liver iron rather than those provided by SQUID, together with T2* cardiac assessment.)
The study concludes that "provided a multidisciplinary team is available, pregnancy is possible, safe and usually has a favorable outcome in patients with thalassemia." The authors are state the need for larger and more detailed studies, especially in thalassemia intermedia.


Download CAF's "Fertility and Pregnancy in Thalassemia" pamphlet by clicking here