Alpha thalassemia major (Hb Bart’s hydrops fetalis)

Alpha thalassemia major is an inherited blood disorder. It is also called hemoglobin Bart hydrops fetalis syndrome, or Hb Bart syndrome. Hemoglobin is the protein in red blood cells that carries oxygen. In this condition, the body cannot make any normal alpha-globin, one of the building blocks of hemoglobin.

Alpha thalassemia also has milder forms. Silent carriers and people with alpha thalassemia trait usually have few or no health problems. Hemoglobin H (HbH) disease causes mild to moderate anemia. Alpha thalassemia major is the most severe form, and it begins before birth.

People normally have four copies of the genes that make alpha-globin: two HBA1 genes and two HBA2 genes. Alpha thalassemia major happens when all four copies are missing or changed. Most often, the genes are deleted, meaning a piece of DNA is missing.

A baby can be affected when both parents carry two missing genes on the same chromosome. When both parents carry this change, each pregnancy has a 1 in 4 chance of alpha thalassemia major. People who carry two missing genes usually have few or no symptoms, so they may not know they are carriers.

Alpha thalassemia is common worldwide, especially in Southeast Asia. It is also found often in people from Mediterranean countries, Africa, the Middle East, India and Central Asia.

Without alpha-globin, a baby makes abnormal hemoglobins instead: hemoglobin Bart’s before birth and hemoglobin H after birth. These hold on to oxygen too tightly, so the body’s tissues do not get enough. The result is severe anemia and low oxygen.

Before birth, the baby’s heart works harder, and fluid can build up in the body. This is called hydrops fetalis. The liver and spleen can become large. Some babies have heart differences or differences of the urinary system or genitals. Without treatment, most babies are stillborn or die soon after birth.

The pregnancy can also be dangerous for the mother. Risks include very high blood pressure with swelling (preeclampsia), a related condition called mirror syndrome, early delivery and abnormal bleeding.

Diagnosis often starts before pregnancy, with the parents. A routine complete blood count (CBC) can show small red blood cells, which is a clue that a person may carry alpha thalassemia. A DNA test is needed to confirm it. Standard hemoglobin tests (electrophoresis or HPLC) cannot find alpha thalassemia carriers.

If both parents carry two missing genes on the same chromosome, the baby can be tested during pregnancy. Chorionic villus sampling (CVS) is done at about 10 to 14 weeks, and amniocentesis after about 16 weeks. Each carries a small risk of miscarriage. Testing embryos during IVF (preimplantation genetic testing) is another option for a future pregnancy.

Sometimes the first sign is an ultrasound that shows fluid build-up (hydrops) or a large heart. Experts advise quick testing of the baby’s blood from the umbilical cord for hemoglobin Bart’s. A first transfusion can be given at the same time, so treatment does not wait for other test results.

Treatment can start before birth. Doctors give the baby red blood cells through the umbilical cord (intrauterine transfusions). Specialist centers can usually start at about 18 weeks of pregnancy. In a U.S. study, transfusions were repeated every 2 to 3 weeks until delivery.

After birth, care is much like care for beta thalassemia major. Children get red cell transfusions about once a month, plus medicine to remove extra iron (iron chelation). Transfusions often aim higher than usual to hold down the body’s own nonworking hemoglobin H. Early results suggest iron medicine can be started safely after about 1 year of age, with close checks.

A donor stem cell transplant can cure the condition by replacing the blood-making system. It needs strong chemotherapy first (conditioning) and carries serious risks, including graft rejection and graft-versus-host disease.

No gene therapy is approved for alpha thalassemia. The approved gene therapies for thalassemia are for beta thalassemia. Gene therapy for alpha thalassemia is still in early studies.

Many families learn about alpha thalassemia major during pregnancy, sometimes after an ultrasound shows fluid build-up. Parents face hard choices in a short time. Expert groups say counseling should not push parents in any direction. It should cover waiting and watching, ending the pregnancy, or fetal transfusions. Because untreated hydrops can harm the mother, experts discourage simply waiting.

Fetal transfusions are done at specialist centers, so some families travel for care. Delivery is usually planned at a hospital with a newborn intensive care unit. Most babies who survive need lifelong transfusions unless they have a successful transplant.

Life after birth includes transfusion visits every few weeks, iron checks, and checks of growth and development. Many boys are born with hypospadias, a difference in where the opening of the penis is, which surgery can correct. Families may also weigh a transplant, with its long hospital stay and years of follow-up.

A donor transplant gives the child healthy blood-forming stem cells that can make normal hemoglobin. In published reports, donors have included matched and mismatched brothers and sisters, unrelated volunteers, cord blood and, in one Hong Kong series, a mother.

A well-matched donor can be hard to find. When no brother or sister matches, an unrelated donor may make a cure possible. European transplant guidelines (EBMT, 2025) cover children with transfusion-dependent thalassemia. For those without severe organ damage from iron, they rate a matched sibling or matched unrelated donor transplant as standard care.

In a U.S. trial, babies received their mother’s stem cells before birth. It was safe, but the mother’s cells did not take hold in a useful amount, and the trial stopped enrolling. UCSF notes that tolerance to the mother’s cells fades after birth, so she may not be a suitable donor later.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

Alpha thalassemia major was once thought to be always fatal. Without treatment, most babies die before or soon after birth. With fetal transfusions and newborn intensive care, more babies now survive into childhood and beyond. In a U.S.-led registry, babies who had 2 or more fetal transfusions did better than those who had 0 or 1.

Survivors have a lifelong condition. They need regular transfusions and iron removal unless a transplant works. In an international registry, many children were small for their age, and some had serious developmental delays. Experts say survivors may face more complications than people with beta thalassemia major, from anemia, low oxygen, iron build-up and their treatments.

A donor transplant can end the need for transfusions. In the same international registry, most children who had a transplant became transfusion-free, but some transplants failed and one child died. None of these numbers can predict how one child will do.