What is Alpha Thalassemia?
Hemoglobin is a part of your blood made from iron and protein. Its job is to transport oxygen from your lungs to other parts of your body. In adults, there are normally three main kinds of hemoglobin: Hemoglobin A, Hemoglobin A2, and Hemoglobin F. These different types are determined by how they are combined with other molecules called alpha, beta, gamma, or delta.
Hemoglobin A, which makes up the majority of adult hemoglobin, has one pair of alpha and beta chains. Hemoglobin A2 is composed of alpha and delta chains, making up a smaller amount of adult hemoglobin. Hemoglobin F, which uses alpha and gamma chains, is mainly found in newborn babies, but a small amount is also present in adults. However, the amounts can vary depending on a person’s age, genetics, medication, and health conditions.
Thalassemias are a group of disorders that occur when the body has trouble making parts of hemoglobin known as globin chains. This can mean less hemoglobin is produced, leading to a condition called erythropoiesis where the body’s red blood cells are destroyed inside the bone marrow. If this happens with the alpha globin chains, it’s termed as Alpha thalassemia.
This disorder is associated with over 15 different genetic mutations. The severity of the condition varies depending on the type of mutation and if one or both locations of the alpha-globin part are affected. There are two types of mutations: deletion and non-deletion. Deletion is when just one alpha-globin gene is passed on, while non-deletion is when a patient gets two alpha-globin genes, but one carries an abnormality. In non-deletion cases, the impact on health depends on whether the mutation partially or fully stops the production of normal alpha chains.
A condition called Hemoglobin H disease happens when only one normal alpha gene is inherited. Hemoglobin Constant Spring is a common subtype of this disease. Patients with non-deletion types of Hemoglobin H disease generally have more severe symptoms, most likely because the abnormal gene interrupts the function of the normal alpha chain gene.
What Causes Alpha Thalassemia?
Hemoglobin H develops when a person only gets one normal alpha gene. This significantly affects the production of alpha globin, a part of hemoglobin, the protein in our red blood cells that carries oxygen. During the newborn phase, this causes a surplus of gamma globin, another part of hemoglobin. However, in adults, it leaves an excess of beta-globin chains, yet another part of hemoglobin.
Alpha chains by themselves are not soluble, meaning they don’t dissolve in fluids. On the other hand, both gamma and beta chains do dissolve and can form homotetramers, groups of four identical molecules.
Hemoglobin H in adults is composed of four beta chains, while a type of hemoglobin called HbBarts consists of four gamma chains. But these types of hemoglobin are unstable and can clump within the red blood cells, causing a range of symptoms. Hemoglobin H can make up to 40% of total hemoglobin in individuals with this condition.
This form of hemoglobin is more sensitive to injury from oxidative substances and doesn’t carry oxygen as effectively. It has ten times more affinity, or attraction, to oxygen than regular Hemoglobin A, yet doesn’t transport it to body tissues as it normally should due to an abnormal binding and releasing pattern, known as an abnormal oxyhemoglobin dissociation curve. This means it can attach itself to oxygen, but doesn’t supply it to tissues effectively.
Risk Factors and Frequency for Alpha Thalassemia
Alpha thalassemia traits, which are believed to help protect against malaria, can be found in up to 90% of populations in areas where malaria is common. This trait is similar to Hemoglobin H, which is usually found in warmer climates. The most cases are seen in Southeast Asia, the Mediterranean, and the Middle East. A form of alpha thalassemia called Hemoglobin Constant Spring, which doesn’t involve gene deletion, is rather common.
- 1% to 2% of people in northeastern Thailand have Hemoglobin Constant Spring.
- 5% to 8% of people living in southern China have Hemoglobin Constant Spring.
- 25% of women from a certain ethnic minority in Vietnam are found to have Hemoglobin Constant Spring.
Signs and Symptoms of Alpha Thalassemia
HbH disease is a type of alpha thalassemia, a blood disorder that can range from moderate to severe. The severity of the condition can vary a lot because of different types of genetic changes. Some patients might not show any symptoms, while others might have intermittent anemia, requiring blood transfusions. In extreme cases, it can cause a deadly condition for fetuses called hydrops fetalis.
The first signs of the disease usually emerge late in pregnancy with the development of hemolytic anemia, a condition where red blood cells are destroyed faster than they are made. In the worst-case scenario, it can lead to hydrops fetalis, resulting in fetal death. At birth, the newborns usually have jaundice (a yellowing of the skin and eyes) and anemia (a deficiency of red cells or of hemoglobin in the blood).
As patients grow older, their anemia can vary in severity. The anemia is due to the body not creating enough red blood cells and existing ones being destroyed. Conditions that increase oxidative stress, such as sepsis (a life-threatening response to infection) or certain medication, can speed up the rate at which red blood cells are destroyed. Patients may then have symptoms common to hemolytic anemia, such as:
- Jaundice (yellowing of the skin and eyes)
- Indirect hyperbilirubinemia (higher than normal level of bilirubin, a waste product, in the blood)
- Elevated levels of lactate dehydrogenase (LDH, an enzyme found in the body)
- Lowered haptoglobin (a protein that binds free hemoglobin released from red blood cells)
- Enlarged spleen (splenomegaly) and liver (hepatomegaly)
- Involved bony changes
- Early bile duct disease
- Leg ulcers (open sores)
- Iron overload if multiple blood transfusions are required without proper iron chelation (therapy to remove excess iron from the body)
In adults, suspicion of the disease often occurs in patients showing signs of anemia where red blood cells are smaller than normal, but who have normal iron levels and a normal hemoglobin A2 level on electrophoresis, a test that separates proteins based on their size and charge. They usually have hemoglobin levels ranging from 8 to 10 g/dL under normal conditions.
Testing for Alpha Thalassemia
In HbH disease, a blood test can show certain changes in your red blood cells – they may have less color (hypochromia) and be smaller than usual (microcytosis). These cells can also carry something called ‘inclusion bodies’. These inclusion bodies can be seen more clearly if the laboratory uses special dyes, like methyl violet or brilliant cresyl blue.
The disease can also affect your bone marrow – the soft, spongy tissue inside your bones where blood cells are made. The bone marrow might be making too many the red blood cells (erythroid hyperplasia), and these newly formed cells can be poorly filled with hemoglobin and might also contain inclusion bodies.
To confirm if someone has HbH disease, the doctor may order a hemoglobin test. This test uses electrophoretic or chromatographic techniques, basically, specialized lab processes that help identify and measure HbH, a type of hemoglobin associated with this disease.
However, for a precise diagnosis, DNA-based genotyping is needed. This involves analyzing your genetic material or DNA. This test is especially important if you’re planning a family, because it can provide information for prenatal testing and genetic counseling.
Treatment Options for Alpha Thalassemia
If a patient has hemolytic anemia, doctors often suggest taking supplements like folic acid. Hemolytic anemia is a condition where the body’s red blood cells break down faster than they can be produced. Folic acid helps the body produce new red blood cells, making it important for treating this condition. Patients with a condition known as HbH are at risk of experiencing harmful effects due to oxidative damage, which happens when harmful molecules called free radicals build up in the body and cause damage to cells.
It’s crucial for these patients to have their blood counts monitored frequently. This is because they may need blood transfusions during times when their body is under stress. Such stress can come from infections or from using drugs that increase the level of damaging molecules in the body.
Patients on regular blood transfusions also need to be carefully checked for complications associated with chronic transfusions. Too many transfusions can cause an overload of iron in the body. So, such patients may need help managing their iron levels, usually provided through substances called iron chelators. This form of support is particularly essential in their second and third decades of life.
Finally, patients should receive thorough genetic counseling. This means discussing with a health professional about inherited diseases, understanding risks and consequences and informing about the possible healthcare decisions that can be made accordingly.
What else can Alpha Thalassemia be?
When doctors are diagnosing thalassemia, a type of blood disorder, there are a few key conditions they need to consider and rule out first. This list includes:
- Iron deficiency
- Beta thalassemia
- Combinations of sickle cell disease and thalassemia
It’s important to cross out these possibilities to ensure an accurate diagnosis of thalassemia.
Preventing Alpha Thalassemia
Young patients who are considering having a baby need to go through genetic counseling. This is a process where experts explain the potential effects of their genes on their child. It’s also essential to educate these patients about the effects of having too much iron in their body, which is known as ‘iron overload’. They should understand the importance of sticking to their treatment plan to manage this condition properly.