Thalassemia

What is Thalassemia?

Thalassemias are a group of inherited blood disorders that occur when the body doesn’t create enough of one or both types of proteins needed to make hemoglobin, the substance in red blood cells that carries oxygen throughout the body. These proteins are known as the alpha and beta chains. If not enough of them are made, red blood cells can’t form properly or carry enough oxygen, resulting in anemia that starts in early childhood and continues throughout life. This disease is inherited, which means that at least one parent has to be a carrier for it. It’s caused by genetic mutations or the deletion of certain genes.

Thalassemia comes in two types: alpha thalassemia and beta thalassemia. Alpha thalassemia is caused by the deletion of the alpha-globin gene, which leads to less or no production of alpha-globin chains. There are 4 versions of this gene and the severity of the disease depends on how many are deleted. If all 4 are deleted, it’s the most severe form, with no alpha globins produced at all and the formation of a substance known as tetramers from excess gamma chains (present during the fetal period). This severe form is not compatible with life.

Beta thalassemia, on the other hand, results from mutations in the beta-globin gene. There are three severity levels, based on the type of beta-gene mutation. If there is a mutation in one beta-globin gene (beta-plus thalassemia), it results in a milder form where fewer beta chains are made. This is often symptomless. A mutation in both beta-globin genes (beta-zero thalassemia) means no beta chains are made at all, leading to severe symptoms like jaundice, delayed growth, enlarged liver and spleen, abnormal hormone levels, and severe anemia that requires regular blood transfusions throughout life. There’s also a form of the disease with symptoms that are between mild and severe, known as beta-thalassemia intermedia.

Specifically, if you have one mutated gene, you’ll have mild signs and symptoms (known as thalassemia minor); if you have two mutated genes, your signs and symptoms will be moderate to severe (known as thalassemia major or Cooley anemia).

When someone with beta-thalassemia creates too many alpha-globin chains, the chains can clump together and damage red blood cells, leading to the destruction of red blood cell precursors. This is called ineffective erythropoiesis and can later lead to the abnormal expansion of the production of new blood cells outside the bone marrow.

Sometimes, a person with beta-thalassemia also has alpha thalassemia, which can actually result in less severe symptoms due to a better balance between alpha and beta. However, if a person with beta-thalassemia also has a sickle cell trait, it creates a significant blood disorder that results in symptoms similar to sickle cell disease.

There’s also a common variant of hemoglobin, HbE, found in Southeast Asia. This variant is often found in people with thalassemia in this region.

A new way of classifying thalassemias is in terms of whether they require blood transfusions to treat or not, where there’s ‘transfusion requiring’ and ‘non-transfusion requiring’ thalassemias.

What Causes Thalassemia?

Thalassemia is a genetic disease, which means it is passed down from parents to their children. For a child to have the disease, both parents have to either have the disease or carry the gene. Thalassemia is caused by specific changes in the genes that help create hemoglobin, a protein that carries oxygen in the blood. This leads to a shortage or an absence of certain building blocks – called alpha or beta chains – that make up hemoglobin.

The medical world has identified over 200 different changes in genes that can cause thalassemias. Alpha thalassemia is caused by deletions of alpha-globin genes – a part of the genetic code that affects the alpha chains. On the other hand, beta thalassemias are due to a specific type of mutation in the beta-globin gene, which is important in creating the beta chains. This gene is situated on chromosome 11, one of the many ‘X-shaped’ parts of a cell that carry our genetic information.

Risk Factors and Frequency for Thalassemia

Alpha thalassemia is a condition that is commonly found in Asian and African populations. On the other hand, beta-thalassemia is typically seen more in the Mediterranean population. However, it is also quite prevalent in Southeast Asia and Africa, with reports suggesting that up to 10% of people in these regions could be affected. The exact number of people suffering from thalassemia in the United States is not known, as there isn’t an effective way to screen for it.

Signs and Symptoms of Thalassemia

Thalassemia, a blood disorder, can show up in different ways depending on its type and seriousness. Some signs and symptoms may not even be noticed by the patient. Here are some things to look out for:

• Skin: Pallor (due to anemia), jaundice (due to excessive bilirubin from broken down red blood cells), and possibly even bronze skin due to frequent blood transfusions. The patient might also complain of tiredness (a result of the anemia) and have sores on their extremities.
• Musculoskeletal: The patient might have a distorted facial appearance and other bone deformations due to an unusually high expansion of blood cell creation in the bone marrow.
• Cardiac: Heart rhythm disruptions can occur due to iron build-up in heart cells from frequent blood transfusions. Chronic anemia can also lead to outright heart failure.
• Abdominal: Symptoms may include typical abdomen pain due to gallstones caused by an excess of bilirubin. Enlarged liver and spleen can occur due to chronic iron build-up and abnormal blood cell creation in these organs.
• Hepatic: Liver problems are common in thalassemia, especially because patients need regular transfusions. This could lead to chronic liver failure or cirrhosis, due to iron build-up or transfusion-related viral hepatitis.
• Slow Growth Rates: Anemia can slow a child’s growth, and thalassemia can cause delayed puberty. It’s important to monitor a child’s growth and development progress.
• Endocrinopathies: Too much iron can decrease the functions of various organ systems. Iron build-up in the pancreas can cause diabetes, accumulation in the thyroid or parathyroid glands can lead to hypothyroidism and hypoparathyroidism. Iron can also accumulate in the joints leading to chronic arthritis. In the brain, it can manifest as early-onset Parkinson’s disease and other physical impairments.

Testing for Thalassemia

If a doctor suspects that a patient has thalassemia, a common blood disorder, they will use various lab tests to confirm their suspicion. Here’s what to expect:

A Complete Blood Count (CBC): This is typically the first test done when thalassemia is suspected. It tests for things like the amount of hemoglobin and Mean Corpuscular Volume (MCV) in the blood. Hemoglobin is what allows your red blood cells to carry oxygen, and MCV measures the average size of your red blood cells. If these numbers are low, it may be a sign of thalassemia, although the doctor will also need to rule out iron deficiency as the cause of the anemia.

A peripheral blood smear: This is a way to look directly at the blood cells under a microscope, which may reveal features consistent with thalassemia such as cells of varying size and shape, and an increased number of immature red blood cells (reticulocytes).

Iron studies: These are needed to exclude iron deficiency anemia. Iron is essential for your body to make hemoglobin.

Erythrocyte porphyrin levels: Your doctor might order this test to separate thalassemia from iron deficiency or lead poisoning. People with thalassemia will have normal levels of these substances in their blood whereas those with iron deficiency or lead poisoning will see these levels increase.

Hemoglobin electrophoresis: This test measures the different types of hemoglobin in red blood cells. In people who have thalassemia, the balance between different types of hemoglobin is usually off. For example, HbA, the most common type of hemoglobin, might be low or missing altogether, while other types (like HbF and HbA2) are present in larger amounts.

DNA analysis: Thalassemia is caused by mutations in certain genes, so examining these genes can help confirm a diagnosis and determine if other family members are carrying the same abnormal gene.

Genetic testing of amniotic fluid: If a fetus is at high risk for thalassemia, the doctor might check the genetic makeup of cells in the amniotic fluid, the fluid that surrounds the fetus in the womb. This is particularly useful if both parents are carriers of the gene mutation that causes thalassemia as it increases the risk of the child inheriting both abnormal genes, which can cause a more severe form of the disease.

Regular multisystem evaluations: Since thalassemia can affect many different systems in the body, regular evaluations are essential. These could include imaging of the gall bladder and bile ducts, ultrasound of the abdomen, cardiac MRI, and regular hormone measurements among other things based on the patient’s specific case.

Treatment Options for Thalassemia

Thalassemia is a condition that affects the body’s ability to produce healthy blood cells. Below is a breakdown of the treatments depending on the severity of the thalassemia.

Mild Thalassemia:

In mild thalassemia, symptoms are small and many times, no treatment is needed. However, sometimes patients may need a blood transfusion during certain situations such as after surgery, after childbirth, or when complications of thalassemia occur.

Moderate to Severe Thalassemia:

If the thalassemia is more severe, frequent blood transfusions might be needed, sometimes every few weeks. This helps maintain normal blood levels, which helps patients feel their best and keeps their body producing blood in a normal way.

Chelation Therapy:

Chelation therapy is treatment to remove extra iron from the body. Iron can build up in people receiving chronic blood transfusions. To prevent health problems, iron chelators, a type of medication, can be used to remove the excess iron.

Stem Cell Transplant:

A stem cell transplant, which is also called a bone marrow transplant, might be an option for certain severe thalassemia cases, such as in young children. This procedure can eliminate the need for lifelong blood transfusions but also comes with its own set of risks, such as the transplanted cells being attacked by the immune system.

Gene Therapy:

A recent advancement in treating severe thalassemia is gene therapy. This involves taking the patient’s own blood-producing cells, modifying them to produce normal genes and reintroducing them back into the patient’s body. This leads to the production of normal blood cells.

Genome Editing Techniques:

Another recent advancement is using various techniques to target specific mutation sites in the genes and replace them with normal sequences.

Splenectomy:

A splenectomy, or the removal of the spleen, might be done to reduce the number of needed transfusions. It is typically recommended when a patient requires a large amount of blood transfusions per year. After splenectomy, specific vaccinations are needed to prevent certain infections, and in young children, antibiotics may be given until they reach a certain age.

Cholecystectomy:

In patients who develop gallstones due to increased breakdown of blood cells and buildup of a substance called bilirubin in the gallbladder, removal of the gallbladder (cholecystectomy) might be needed.

Diet and Exercise:

Some reports suggest that drinking tea and taking small amounts of vitamin C along with iron chelators can be beneficial for people with thalassemia. Drinking tea might help limit iron absorption from the gut, while vitamin C could aid in iron excretion. However, large amounts of vitamin C without concurrent use of iron chelators might pose risks such as irregular heart rhythms, hence, only small amounts are recommended.

What else can Thalassemia be?

Anemia can be caused by various conditions, and it’s necessary to rule out these possibilities before arriving at the correct diagnosis.

• Iron deficiency anemia: The doctor can rule this out by looking at iron levels in the body and using a diagnostic process called the Mentzer index.
• Anemia due to chronic disease and kidney failure: This is suggested if the levels of inflammation markers (CRP, ESR) in your body are high.
• Sideroblastic anemias: Doctors can check for this by examining iron levels and a blood sample under a microscope.
• Lead poisoning: Doctors can rule this out by measuring the levels of a substance called protoporphyrin in the bloodstream.

What to expect with Thalassemia

Thalassemia minor is a condition that typically does not show any symptoms and has a positive outcome. It does not generally increase the risk of illness or death.

On the other hand, Thalassemia major is a serious condition. The long-term outcome heavily depends on how strictly a person follows their treatment plan, including blood transfusions and therapies that help to remove excess iron from the body.

Possible Complications When Diagnosed with Thalassemia

Thalassemia major, a type of blood disorder, may lead to various complications:

• Yellowing of the skin and eyes, also known as jaundice, and gallstones due to an excessive amount of bilirubin
• Weakening and deformity of the bones as a result of production of blood cells outside the bone marrow (extramedullary hematopoiesis)
• Strains on the heart leading to heart failure, heart muscle diseases and irregular heart rhythms because of severe anemia; these heart-related issues are the major cause of death among people with Thalassemia
• Enlarged liver and spleen due to both extramedullary hematopoiesis and an accumulation of iron from repeated blood transfusions
• Side effects of too much iron in the body such as hormonal disorders, joint issues, skin discoloration, and others which are similar to symptoms of a condition called primary hemochromatosis
• Nerve damage, referred to as peripheral neuropathies
• Delayed growth and puberty
• Increased risk of catching the parvovirus B19 infection

Preventing Thalassemia

Patients should be aware of their condition and play an active role in managing it by following the treatment plan and maintaining a healthy lifestyle.

Here are some tips:

• Avoid too much iron. Unless your doctor says otherwise, you should stay away from multivitamins or other supplements that have iron in them. This is because an excess of iron can worsen your condition.
• Eat a healthy diet. Consuming nutritious food can make you feel healthier and more energetic. Sometimes, doctors also suggest taking a supplement called folic acid which aids in the creation of new red blood cells.
• Avoid getting sick. It’s crucial to do your best in avoiding infections, especially if you’ve had a procedure called a splenectomy. Doctors recommend getting vaccines against the flu, meningitis, pneumococcal disease, and hepatitis B to help prevent these infections.

Patients should also be aware that their condition is hereditary, which means it can be passed down from parents to their children. For instance, if both parents have a minor form of this condition known as thalassemia minor, there is a chance that their child could have a severe form of this condition known as thalassemia major. If one parent has minor beta-thalassemia and the other has some form of a defect in the beta-globin gene, such as a sickle cell defect, they should also know about the risk of passing the condition on to their children.

It’s important for patients with this condition to understand that it is not caused by iron deficiency. Taking iron supplements won’t cure the anemia associated with this condition, but will actually cause more iron to build up in their bodies if they are already receiving blood transfusions.