What is Beta Thalassemia?
Thalassemias are a common reason behind anemia, a condition where the body produces smaller and fewer red blood cells that are lighter in color. This happens because there’s a decrease or complete absence of the globin protein which is a major component of hemoglobin in our blood. Hemoglobin is vital as it carries oxygen in our red blood cells. Unlike diseases like sickle cell disease that are caused by flawed hemoglobin, thalassemias primarily affect the amount of hemoglobin.
One kind of thalassemia is Beta-thalassemia, which is caused by a genetic mutation that affects the production of the beta-globin protein. This genetic mutation is most common in people of Mediterranean, Middle Eastern, and Asian descent. More than 200 different mutations have been discovered in the beta-globin gene, causing a wide range of symptoms and severity.
Beta-thalassemia is classified into three categories based on their symptoms and lab results. Beta-thalassemia minor or the carrier trait usually shows no symptoms and may cause mild anemia. A person with two sets of beta-thalassemia mutations can have severe forms of anemia, referred to as beta-thalassemia intermedia and beta-thalassemia major. Beta-thalassemia major patients need regular blood transfusions, whereas those with intermedia do not.
Tests for thalassemia usually reveal anemia with red blood cells that are smaller and lighter in color. In severe forms like Beta-thalassemia major, the cells may also vary in size and shape. Additional tests to exclude iron deficiency, and technical tests to understand the type of hemoglobin could also be necessary for diagnosis. If treatment is required, it often involves blood transfusions depending on how severe the anemia is. Possible complications of beta-thalassemia include excess iron in the body and abnormal expansion of bone marrow.
What Causes Beta Thalassemia?
Beta-thalassemia is a condition you can inherit from your parents. It happens when there are changes or, rarely, deletions in a specific gene known as the beta-globin gene (HbB) on chromosome 11. This gene has over 200 identified changes that can lead to the disease. The changes in the gene either affect how it’s controlled, how it’s translated, or how it’s spliced and these processes are critical in the functioning of the gene.
The severity of the disease is determined by two facts: each person has two copies of the beta-globin gene (one inherited from each parent), and there’s a wide range of disease-causing mutations. There’s also variability, meaning that the beta-globin synthesis can be slightly reduced (referred to as beta(+)) or completely absent (referred to as beta(0)).
Beta-thalassemia is broken down into minor, intermedia, and major, based on symptom severity. Beta-thalassemia minor occurs when one beta-globin gene is affected, and one is not, and this can either lead to reduced synthesis (beta(+)) or no synthesis (beta(0)) at all.
If both beta-globin genes are affected or have either reduced or no synthesis, this would lead to either beta-thalassemia intermedia or major. The difference between these two is not genetic but instead depends on the severity of anemia (a condition where your blood doesn’t have enough red blood cells).
Risk Factors and Frequency for Beta Thalassemia
Beta-thalassemia is a condition that shows up more frequently in certain parts of the world. It’s most common in the Mediterranean, the Middle-East, and parts of Asia. Every year, about 68,000 kids are born with this condition. Plus, it’s estimated that between 80 and 90 million people are carriers of beta-thalassemia, which adds up to roughly 1.5% of the global population.
- Areas such as Cyprus have a particularly high number of carriers, with up to 15% of the Greek and Turkish populations affected.
- The reasons for this include the parallel prevalence of malaria, as there’s a theory that carrying the trait for thalassemia can provide some protection from malaria. This could be why these genes are more common in areas where malaria is also prevalent.
- Other factors include gene drift and the founder effect, where specific genes become more common in a population due to a limited group of initial ancestors.
Signs and Symptoms of Beta Thalassemia
Beta-thalassemia minor is often identified when routine blood tests are conducted. People with this condition might experience light symptoms of anemia, but there are usually no significant physical signs.
For those with beta-thalassemia major, the diagnosis is usually determined between 6 to 24 months of age. These individuals shift from producing fetal hemoglobin to adult hemoglobin and as a result, they experience severe anemia. Symptoms of this type of beta-thalassemia manifest as various health issues: feeding difficulties, irritability, failure to thrive, paleness, diarrhea, recurrent fevers, and enlarged liver and spleen. If not treated properly, infants, particularly those living in resource-poor regions, might experience delayed growth, jaundice, darkened skin pigmentation, poor muscle development, leg deformities and ulcers, abnormal growths from extramedullary hematopoietic sites, and skeletal deformities. The common skeletal issues include frontal bossing, maxillary hypertrophy, and deformities of the long bones.
Beta-thalassemia intermedia covers a spectrum of clinical symptoms but isn’t serious enough to necessitate regular blood transfusions. Children as young as two years may face developmental and growth delays. In milder adult forms, it may first show up as fatigue and paleness. Beta-thalassemia intermedia may also present physical signs suggestive of overactive red blood cell production and extramedullary hematopoiesis (similar to beta-thalassemia major), but in this case, the body compensates for the anemia without requiring transfusions. Patients with long-term hemolysis in beta-thalassemia major and intermedia may show signs and symptoms of gallbladder disease due to gallstone formation.
Testing for Beta Thalassemia
Beta-thalassemia major, a type of blood disorder, is often diagnosed in children under 2 years old. Children with it typically have small and pale red blood cells (microcytic anemia), mild skin yellowing (jaundice), and enlarged liver and spleen (hepatosplenomegaly).
To confirm this diagnosis, doctors use a test called complete blood count (CBC), which examines various components of the blood. If a child has beta-thalassemia major, the CBC will show a very low level of hemoglobin – the oxygen-carrying protein in red blood cells. Specifically, if the hemoglobin level is less than 7g/dl, it suggests beta-thalassemia major.
The CBC will also show more details of the red blood cells: the average size of them (mean corpuscular volume or MCV) will be between 50 and 70 fl, and the amount of hemoglobin in them (mean corpuscular Hb or MCH) will be between 12 and 20pg. If these readings vary, it may suggest different types of thalassemia.
In the minor form of the disease, beta-thalassemia minor, there could be elevated red cell number, with reduced MCV, MCH, and the red cell distribution width (RDW) – the range of sizes of the red blood cells – will typically show low elevations. An elevated RDW could indicate other similar conditions, like iron deficiency anemia or sideroblastic anemia where the RDW is typically very high.
Further, the CBC will also look at a small drop of your blood under a microscope (peripheral blood smear). In beta-thalassemia, red blood cells can be small and pale (microcytic hypochromic anemia), or shaped like a teardrop. In severe cases, the red blood cell shape can vary significantly (anisopoikilocytosis), and there can be red cells with nucleus (nucleated red blood cells).
However, the CBC and peripheral smear are not specific for thalassemia. So, to confirm the diagnosis, doctors will need another test that looks at the types of hemoglobin in your blood (hemoglobin electrophoresis or high-performance liquid chromatography). In beta-thalassemia, there is often a decrease in the normal adult hemoglobin (HbA), a mild increase in another type of hemoglobin (HbA2), and sometime an increase in fetal hemoglobin (HbF), which normally decreases after birth. The degree to which these changes occur can depend on specific gene mutations.
Sometimes, if a patient also has iron deficiency, the results from hemoglobin electrophoresis can look normal, and beta-thalassemia minor may be missed. Other conditions that could show similar results include antiretroviral therapy, deficiencies in vitamin B12 or folate, hyperthyroidism, and other blood disorders. The difference between beta-thalassemia major and the less severe version, beta-thalassemia intermedia, cannot be clearly distinguished by these tests, and it is mostly determined by the doctor’s examination.
Treatment Options for Beta Thalassemia
Thalassemia is a genetic blood disorder. If you have thalassemia minor, it means you’re a carrier for the disease but you usually won’t have symptoms. It’s important to have genetic counseling and get tested when you’re pregnant if you have thalassemia minor, to see if your baby is at risk of having the disease.
Thalassemia major, a more severe form of the disease, is treated with transfusions of red blood cells. These transfusions aim to reduce the body’s own production of red blood cells – which are faulty in people with thalassemia – and to lighten the symptoms of anemia (such as tiredness and weakness) and to lower the iron absorption in your stomach. Doctors might suggest a transfusion if the patient has severe anemia, growth delays, or expanding bone marrow and spleen, shown by symptoms like facial changes, bony expansion, and an enlarged spleen.
However, repeated blood transfusions can lead to an overload of iron in the body and other related problems. Other potential risks include reactions to the transfusion and the development of antibodies that can make it harder to find suitable blood for future transfusions.
There’s a potential cure for beta-thalassemia, and that’s a bone marrow or cord blood transplant. A stem cell transplant from a sibling who is a full genetic match can offer more than a 90% chance of disease-free survival in patients without complications. Cord blood, which contains stem cells, can be collected after a new baby is born and transplanted to a sibling with thalassemia if they’re a genetic match.
People who have regular transfusions need to have their iron levels checked, as they can build up to toxic levels in the body. The checks for overload are usually based on visual examinations for the signs of iron buildup and on consistent blood tests for ferritin, a blood protein that contains iron. When patients have received 10 to 20 transfusions or when their blood ferritin levels exceed 1000 ng/mL, doctors usually recommend iron chelation therapy, a treatment that helps to remove excess iron from the body.
Other nutritional problems related to thalassemia can include shortages of folic acid, calcium, and vitamin C. Patients frequently experience symptoms related to an enlarged spleen – a condition called hypersplenism – which can be treated through surgery to remove the spleen. However, without a spleen, patients are more vulnerable to infections and require appropriate vaccinations.
Patients with beta-thalassemia major must regularly follow up with their doctor to monitor their body’s response to transfusion therapy and any side effects from iron chelation therapy. This usually involves regular physical examinations, blood tests, growth assessments in children, and checks for vision and hearing. Other checks include annual assessments of the heart, thyroid, parathyroid, endocrines, adrenal glands, and pancreas, alongside liver ultrasounds, bone density scans, and checks for early signs of liver cancer. Depending on the degree of iron overload, MRI scans of the liver and heart may also be required to evaluate the amount of excess iron.
What else can Beta Thalassemia be?
If someone has hypochromic microcytic anemia (a type of anemia causing pale, small red blood cells), it could be a symptom of several conditions. Doctors will want to consider the following potential causes:
- Alpha thalassemia (a blood disorder causing lowered hemoglobin production)
- Anemia of chronic disease (anemia associated with long-term medical conditions)
- Iron deficiency anemia (anemia due to a lack of iron)
- Sideroblastic anemia (a condition lowering the body’s ability to use iron to produce hemoglobin)
- Lead nephropathy (kidney damage due to exposure to lead)
Beta-thalassemia, another blood disorder, is different from sideroblastic anemias as it doesn’t cause ring sideroblasts in the bone marrow (an atypical form of red blood cell) and it doesn’t increase levels of a substance called erythrocyte protoporphyrin. To rule out iron deficiency, doctors will refer to normal range iron studies which include checking the serum iron, total iron-binding capacity, and percent transferrin saturation. Hemoglobinopathies (a group of blood disorders and diseases which affect red blood cells) usually require a hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) test for diagnosis.
What to expect with Beta Thalassemia
Before the year 2000, the outlook for patients with beta-thalassemia major (a serious blood disorder) was not very positive. In the United Kingdom, about half of these patients passed away before reaching the age of 35. However, since 2000, things have significantly improved. Today, more than 80% of patients with beta-thalassemia major in the UK live past the age of 40.
This improvement is largely due to the development of noninvasive techniques that can detect the amount of iron in organs before any symptoms appear, the creation of new iron-removing drugs (chelators), and enhanced measures to ensure the safety of blood supplies.
Possible Complications When Diagnosed with Beta Thalassemia
: Complications of conditions involving overstimulation of bone marrow, ineffective production of red blood cells, and an excessive amount of iron through blood transfusions, can be quite serious.
For instance, if there is too much iron, it can accumulate in the heart and eventually lead to heart failure. This is the main cause of death in people with a type of blood disorder called beta-thalassemia major (TM). The symptoms experienced by these patients often differ from those without anemia, due to their bodies adapting to chronic anemia. They may frequently experience shortness of breath along with a fast resting heart rate, low blood pressure, high ejection fraction and high cardiac output. Iron can even cause issues like atrial fibrillation, an irregular and often very fast heartbeat, which is more common in TM patients than the general public.
Excess iron may also lead to problems in the endocrine glands, causing a variety of conditions such as:
- Hypothyroidism
- Hypoparathyroidism
- Adrenal insufficiency
- Diabetes mellitus
- Hypogonadism
Thromboembolic, or blood clot-related events, such as deep vein thrombosis, pulmonary embolism, and recurrent arterial occlusion are also more common in those with thalassemia, due to an increased tendency of their blood to clot. This is particularly true in a form of thalassemia named thalassemia intermedia.
Several other complications can occur, including:
- Chronic hepatitis due to infection from blood transfusions
- Cirrhosis due to iron overload
- Hypersplenism
- HIV infection
- Osteoporosis
Preventing Beta Thalassemia
If you have a mild form of a blood disorder called thalassemia minor, it’s important to know that this condition can be passed down through families. This means that your parents, brothers or sisters, and children might also have it. Further, if each of your parents has thalassemia minor, there is a 25% likelihood that your child could have a severe form of the condition known as thalassemia major.
It’s especially critical to seek out genetic counseling—a process that assesses the chance of passing on harmful genes—when one parent has thalassemia minor and the other parent has other diseases related to the beta globin gene, a component of hemoglobin that carries oxygen in the blood. An example of such a disease is the sickle cell trait.
People with thalassemia minor should also understand that taking iron supplements will not help their anemia—a condition where your body has fewer red blood cells than it should or less hemoglobin than normal. This is because their anemia is not due to a lack of iron, but a result of their thalassemia condition.