Myriad Women's Health provides the following resources in select languages:

Myriad Foresight® Carrier Screen

Diseases

alpha thalassemia, HBA1/HBA2-related

What is Alpha Thalassemia, HBA1/HBA2-related?

Alpha thalassemia is an inherited blood disorder that affects hemoglobin. Hemoglobin is a protein found in red blood cells (RBCs) that makes it possible for RBCs to bind and carry oxygen throughout the body. Hemoglobin is made up of two different protein chains, which are referred to as alpha and beta chains or as alpha and beta globin. Alpha thalassemia is caused by harmful genetic changes (mutations) in the HBA1 and HBA2 genes. These genes work together to make the alpha globin protein.

Most individuals inherit two normal copies of the HBA1 gene (one from each parent) and two normal copies of the HBA2 gene. This means that each individual has four gene copies that make up the alpha chain of their hemoglobin (two HBA1 and two HBA2). Individuals can inherit a mutation in one, two, three, or all four gene copies. There are also different types of mutations within the HBA1 and HBA2 genes. Larger mutations that remove most or all of a gene are called “deletional,” while smaller mutations are called “non-deletional.”

The symptoms associated with alpha thalassemia can range from mild anemia to fetal death. The symptoms depend on how many and what types of mutations an individual inherits. Typically, individuals with mutations in more of their alpha globin genes have more severe symptoms. Additionally, non-deletional mutations generally cause more severe symptoms than deletional mutations. Individuals can inherit a combination of deletional and non-deletional mutations.

The different forms of alpha thalassemia are described below. Because there are several forms of alpha thalassemia and the risk for disease depends on a variety of factors, individuals with mutations in  HBA1 and  HBA2  are recommended to consult with a genetics professional to determine both their personal risk for disease and their reproductive risk.

Silent carrier

Silent carriers of alpha thalassemia have a mutation in just one of the four alpha globin genes. Individuals with this finding are known as silent carriers because they typically do not have any disease symptoms or visible abnormalities in their RBCs.

Alpha Thalassemia-trait (carrier)

Carriers of alpha thalassemia have a mutation in two of the four alpha globin genes. Individuals with this finding generally have RBCs that are pale and small when visualized (mild anemia). Individuals with only two functional alpha globin genes normally do not require treatment, as they generally do not exhibit symptoms of disease. However, there are reports of individuals with two non-deletional mutations in HBA1 and/or HBA2 who have a diagnosis of hemoglobin H (HbH) disease (see below). One example of this is when individuals have two copies of the hemoglobin Constant Spring variant, which is common in the Southeast Asian population.

Hemoglobin H disease

HbH disease is typically the result of mutations in three of the four alpha globin genes. This form is highly variable, and symptoms depend on the type of mutations present in an individual. Some individuals with HbH do not have any symptoms, while some may have mild to moderate anemia. Other symptoms of HbH can include fatigue, anemia, yellowing of the skin or eyes (jaundice), enlargement of the spleen, and other more rare or minor complications.

Hemoglobin Bart syndrome

Hemoglobin Bart (Hb Bart) syndrome is typically the result of mutations in all four of the alpha globin genes. Hb Bart is generally associated with fetal death due to the buildup of excess fluid in the body and tissues (hydrops fetalis). Signs and symptoms in the newborn period can include severe anemia, enlargement of the liver and spleen, and birth defects of the heart, urinary system, and genitals. Most babies with this condition are stillborn or die soon after birth. When fetal blood transfusions are successful, survival is possible; however, there is high risk for intellectual and physical disability in these survivors.

How common is Alpha Thalassemia, HBA1/HBA2-related?

The incidence of alpha thalassemia in the population is approximately 1 in 10,000 births. However, the incidence of Hb Bart and HbH is much higher among individuals of Southeast Asian, Mediterranean, and Middle Eastern descent. Southeast Asia has the highest documented incidence, with estimates around 1 in 400 affected births.

How is Alpha Thalassemia, HBA1/HBA2-related treated?

Treatment for HbH disease varies based on the severity of the symptoms. Many individuals will need a blood transfusion during times of severe illness (crises). This is usually a rare occurrence, and it can be caused by environmental stressors such as fever or exposure to specific medications. Individuals with more severe symptoms may require regular blood transfusions, folic-acid supplementation, antibiotics during certain procedures, iron chelation therapy (removal of excess iron from the body), removal of the spleen, and possibly therapies to increase fetal hemoglobin levels.

Rare cases of survivors with Hb Bart syndrome have been reported when fetal blood transfusions were given, followed by regular treatments similar to those given to individuals with HbH disease. Treatment or surgical correction of birth defects may also be possible. There is a high risk for intellectual and physical disability in these survivors. These individuals may be candidates for hematopoietic stem cell transplantation.

What is the prognosis for an individual with Alpha Thalassemia, HBA1/HBA2-related?

The long-term outcome of HbH ultimately depends on the severity of the disease. Mild disease may be manageable with little effect on daily life. However, more severe disease will require frequent and regular therapy and may be associated with a shortened lifespan. When treated, individuals with HbH disease can have a near-normal lifespan.

Hb Bart syndrome is the most severe clinical condition related to alpha thalassemia, and death may occur in utero or in the newborn period. There may also be maternal complications during pregnancy if the fetus has Hb Bart syndrome. These complications include high blood pressure with fluid build-up and protein in the urine (preeclampsia); excessive amniotic fluid (polyhydramnios) or reduced amniotic fluid (oligohydramnios); hemorrhage; and premature delivery. When fetal blood transfusions are successful, survival is possible; however, there is a high risk for intellectual and physical disability in survivors.