AlphaThalassemia Carrier Screening & NIPT

What is UNITY Fetal Risk Screen(™) for alpha-thalassemia?

UNITY Screen (™) starts with carrier screening for alpha-thalassemia to identify carriers who may have an increased risk of having an affected baby. If you are not a carrier, the risk to your baby is minimal. If you are a carrier, the next step is for UNITY Screen (™) to perform single-gene NIPT which tells you what your baby’s risk of having alpha-thalassemia is. While not diagnostic, UNITY Screen (™) offers crucial information for expecting parents to coordinate pre- or post-natal testing if desired.

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The American College of Obstetricians and Gynecologists recommends that anyone planning to start a family or those who are already pregnant be offered carrier screening for inherited conditions, including alpha-thalassemia.

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What is alpha-thalassemia?

Alpha-thalassemia is an inherited condition that affects the red blood cells’ ability to carry oxygen around the body in a molecule called hemoglobin. Hemoglobin is a protein made up of several parts, or subunits, called alpha and beta chains. The genetic instructions to make alpha-chains of hemoglobin are contained in the HBA1/HBA2 genes. If a person has large deletions or smaller changes (non-deletions) in these genes, they can have alpha-thalassemia. The type and severity of symptoms depends on how many copies of the HBA1/HBA2 genes are working. There are two types of alpha-thalassemia that can cause clinical symptoms:

• Hemoglobin H disease: This is a milder form of alpha-thalassemia caused by a person only having one out of four working copies of their alpha-thalassemia genes. Symptoms can vary from person to person, and some people do not have any symptoms or are mildly affected. Others can develop an enlarged spleen, mild jaundice, and mild changes to facial features. In very rare cases, individuals with HbH may require regular blood transfusions.‍
• Alpha-thalassemia major (Hemoglobin Bart disease): This is the most severe form of alpha-thalassemia and is caused by a pregnancy having zero working copies of their alpha-thalassemia genes. Signs of this condition, like the accumulation of fluid in different areas of the pregnancy (hydrops), are usually seen on second and third trimester ultrasounds.

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How is Alpha-Thalassemia Inherited?

Alpha-thalassemia inheritance is complex due to the involvement of multiple genes in hemoglobin production. Two genes, HBA1 and HBA2, are responsible for making the alpha chains of hemoglobin. Each person can have up to two copies of HBA1 and two copies of HBA2, for a total of four alpha-globin genes. The number of functioning copies determines the risk of having an affected baby or the type and severity of alpha-thalassemia if a person is affected.

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Who should consider alpha-thalassemia screening? 

Carrier screening for alpha-thalassemia is recommended for all pregnant individuals or those considering pregnancy. UNITY Screen(™) offers a streamlined solution that combines carrier screening and single-gene NIPT in one test to determine if your pregnancy could be at risk for alpha-thalassemia. You can discuss further genetic testing, either before or after delivery, with your healthcare provider if your UNITY Screen (™) results show an increased risk for alpha-thalassemia. 

Carrier frequencies vary based on ethnicity and the type of alpha-thalassemia their children may be at risk for. 

Silent Carriers: Individuals who have 3 working copies of the HBA1/HBA2 genes. These individuals are not at risk to have a child with Hemoglobin Bart disease. UNITY Screen (™) for silent carriers will tell you about your baby’s risk of having Hemoglobin H disease. 

Other HBA1/HBA2 carriers, excluding silent carriers: Individuals who have 2 working copies of the HBA1/HBA2 genes. These working copies are arranged in different ways which determines what form of alpha-thalassemia a baby may be at risk for. UNITY Screen (™) for these carriers will tell you about your baby’s risk of having either Hemoglobin H or Hemoglobin Bart’s disease based on your individual carrier results.

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UNITY Screen™ Alpha-Thalassemia Screening Workflow

Carrier screening can be done prior to or during pregnancy. If you're pregnant, your doctor can order carrier screening and NIPT at the same time to understand your carrier status and if the baby is at high-risk for any conditions you are a carrier for along with screening for chromosome conditions.

Consult
The UNITY Screen™ NIPT is ordered through your healthcare provider. You can schedule a complimentary genetic counseling session to answer any questions about the test before or after your blood is drawn.

Test: As early as week 9
Your blood sample can be collected in the doctor’s office, at a local lab, or through our mobile services. Your blood sample is shipped to our CAP/CLIA certified laboratory in northern California.

aneuploidy NIPT + fetal antigen results: As early as week 10
Within about one week from lab receipt, your doctor will receive the baby’s risk score for aneuploidies (chromosome conditions) and fetal antigens (if added). You will receive a text or email indicating your results are available on our portal, or your healthcare provider may call you with the results.

carrier status + single-gene NIPT results: As early as week 11
Within about two weeks from lab receipt, your doctor will receive the results of your maternal carrier status testing and single-gene NIPT. If you were found to be a carrier for any of the recessive conditions, single-gene NIPT is automatically run to determine your baby’s risk of being affected. You will receive a text or email indicating your results are available on our portal, or your healthcare provider may call you with the results.

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What do alpha-thalassemia screening results mean?

There are two different forms of alpha-thalassemia (Hemoglobin H disease and Hemoglobin Bart’s disease) that UNITY Screen (™) can assess for based on your specific alpha-thalassemia carrier results. If you are a carrier, single-gene NIPT will be performed and your report will show if your baby has a low risk or high risk of having alpha-thalassemia. If your results show an increased or high risk for a form of alpha-thalassemia, your doctor or genetic counselor will discuss next steps and additional testing options with you.

View sample results

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Frequently Asked Questions

How is alpha-thalassemia treated?

Medical management of alpha-thalassemia includes folic acid supplementation, blood transfusions, medications to reduce extra iron in organs and bone marrow transplants for some patients. Advanced therapies include in-utero blood transfusion and stem cell transplantation.

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What are possible complications of a pregnancy with Alpha-thalassemia major?

In pregnancies with a severe form of alpha-thalassemia major (Hemoglobin Bart disease) an affected baby develops anemia, which can lead to heart failure. When the baby’s heart is working too hard, excess fluid can begin to build up around the heart, lungs, intestines, or under the baby’s skin, this is called fetal hydrops. Hydrops can be seen on second and third trimester ultrasounds.

Additionally, these pregnancies can carry a risk of causing a condition called “maternal mirror syndrome.” When a baby develops hydrops, a mother can mirror these symptoms and develop life-threatening complications like hypertension, swelling in the hands and feet, protein in the urine, fluid in the lungs, and possibly hemorrhage. Babies are typically delivered immediately if this serious condition occurs.

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Treatments & Resources

• Intrauterine Fetal Therapy: Alpha-Thalassemia major - https://fetus.ucsf.edu/intrauterine-therapy-alpha-thalassemia-major/ 
• General Information: Alpha-Thalassemia major - https://fetus.ucsf.edu/alpha-thalassemia/ 
• National Organization for Rare Disorders (NORD): Thalassemia Support Foundation - https://rarediseases.org/organizations/thalassemia-support-foundation/