This is the fifth part of our series about the condition based on our patient booklet “Fast Facts for Patients: Alpha Thalassemia”. This article explains four gene changes in alpha thalassemia (AT).

If you have four gene changes, you have no genes that make alpha chains properly. This is called AT major or Hb Barts disease. This is the most serious form of AT.

What Does This Mean?

When a baby starts to develop in the womb, the first type of Hb its body makes is called embryonic Hb, which doesn’t include any alpha chains. By 16 weeks, the baby begins to make another type of Hb called fetal Hb, which needs alpha chains.

A baby with four gene changes can’t make alpha chains, so fetal Hb cannot develop. Instead, a type of Hb called Hb Barts is made. The baby will develop severe anemia and will die in the womb without treatment. Doctors call this ‘hydrops fetalis’ (or just ‘hydrops’ for short).

It may be possible for the baby to have red blood cell transfusions while still inside the womb (this is called intrauterine transfusion), so the chance of the baby living until birth is greatly increased. However, there is still a high risk of premature birth.

Your health will also be closely monitored throughout your pregnancy. Your medical team will do everything they can to lower the risk of complications for both you and the baby.

What Is the Risk If I Have Children?

If one parent has four gene changes and their partner has two gene changes on the same chromosome, for each pregnancy there is a:

• 1 in 2 chance (50%) the baby will have AT major (four gene changes)
• 1 in 2 chance (50%) the baby will have AT trait (two AT genes on the same chromosome).

If one parent has four gene changes and their partner has two gene changes on different chromosomes, every child will have HbH AT (three gene changes).

If one parent has four gene changes and their partner has HbH AT (three gene changes), for each pregnancy there is a:

• 1 in 2 chance (50%) the baby will have AT major (four gene changes)
• 1 in 2 chance (50%) the baby will have HbH AT (three gene changes).

Please check out the other posts of our series here:

• What Is Alpha Thalassemia?
• Alpha Thalassemia: Genes, Genetic Inheritance and One Gene Change
• Alpha Thalassemia: Two Gene Changes
• Alpha Thalassemia: Three Gene Changes
• Alpha Thalassemia: Screening and Diagnosis
• Alpha Thalassemia: Symptoms and Treatment
• Alpha Thalassemia: Clinical Trials and New Treatments
• Living with Alpha Thalassemia

Information based on Fast Facts for Patients: Alpha Thalassemia (Karger, 2023).