Skip to Main Content
Skip Nav Destination
Vials of Blood

Alpha thalassemia trait often confused for iron deficiency anemia

March 1, 2024

Iron deficiency anemia and alpha thalassemia trait are two common types of microcytic anemia in children, often diagnosed in early childhood during routine hemoglobin examination.

Alpha thalassemia trait is an autosomal recessive genetic blood disorder that affects millions of people worldwide. It is caused by a mutation in the genes that produce the alpha globin chain, one of the two protein chains that make up hemoglobin. This leads to the production of smaller, paler red blood cells.

Alpha thalassemia trait often is misdiagnosed as iron deficiency anemia. It is important for pediatricians to differentiate between the two conditions since iron deficiency anemia needs to be treated promptly, while those with alpha thalassemia trait often need no treatment.

The diagnosis of iron deficiency anemia and alpha thalassemia trait can be made based on a complete blood count (CBC) and other blood tests, including serum iron, total iron binding capacity (TIBC), ferritin and hemoglobin electrophoresis.

Both conditions are characterized by microcytosis (low mean corpuscular volume). Patients with iron deficiency will have a low red blood cell count, high TIBC and low serum iron and ferritin levels. Comparatively, patients with alpha thalassemia trait tend to have an elevated red blood cell count, along with normal or elevated serum iron and ferritin levels, and a normal hemoglobin electrophoresis after the newborn period.

Newborn screening for alpha thalassemia trait

In recent years, many countries have begun to screen newborns for alpha thalassemia trait. However, alpha thalassemia is not a core condition of the United States Recommended Uniform Screening Panel, and only a few states screen for it.

If a baby has alpha thalassemia trait, the newborn screen will show elevated levels of Barts hemoglobin, an abnormal type of hemoglobin produced in the fetus that normally is not present in the blood after birth. If a low quantity of Barts hemoglobin is present at birth, it often disappears shortly after birth, and repeat screening with hemoglobin electrophoresis will not detect its presence.

Additionally, newborn screening cannot differentiate between silent carriers and people with alpha thalassemia trait.

Silent carriers vs. alpha thalassemia trait

Typically, children have four genes for alpha globin, with two genes on each chromosome (αα/αα). Alpha thalassemia silent carriers have one gene missing (αα/α-). They have no signs or symptoms of anemia nor do they require treatment.

Children with alpha thalassemia trait often are missing two genes (αα/--) or (α-/α-) and often present with mild microcytic anemia. The trans form (α-/α-) is more common in children of African descent. The cis form (αα/--) is more common in people of Mediterranean, Middle Eastern and Southeastern Asian descent. Most children with alpha thalassemia trait will not require medical treatment.

Missing three alpha thalassemia genes leads to Hemoglobin H disease (α-/--), which is associated with severe anemia and often requires treatment with red blood cell transfusion and close follow-up with a hematologist. Hydrops fetalis occurs in patients missing all four genes (--/--) and often is fatal in utero.

Alpha globin gene sequencing is used to make a definitive diagnosis of alpha thalassemia silent carrier or trait. Due to cost, however, hematologists typically do not perform genetic testing. Hence, many patients with a microcytosis and a normal hemoglobin electrophoresis and iron panel are presumed to have alpha thalassemia trait or to be a silent carrier.

Benefits of early diagnosis

Early diagnosis helps ensure children with alpha thalassemia trait receive the appropriate management and support. While it is a lifelong condition, it frequently does not cause any health problems or require any treatment. In contrast, patients with iron deficiency anemia require prompt initiation of oral iron supplementation to avoid complications such as delayed growth and development.

Additionally, it is important to provide genetic counseling for those with alpha thalassemia trait, since it can be passed onto offspring.

Guidance for pediatricians

If a newborn screen shows elevated levels of Barts hemoglobin but the baby is asymptomatic, the pediatrician can order a CBC with differential and reticulocyte count and a hemoglobin electrophoresis between 9 months and 1 year of age. The CBC likely will demonstrate microcytosis, suggestive of alpha thalassemia trait/silent carrier. The pediatrician can counsel the family regarding alpha thalassemia trait without referring them to a hematologist.

For children with microcytosis, pediatricians can consider obtaining iron studies and hemoglobin electrophoresis:

  • If the hemoglobin electrophoresis is abnormal, the patient can be referred to a hematologist.
  • If hemoglobin electrophoresis is normal and the iron panel and ferritin level are low, the pediatrician can initiate iron supplementation and monitor ferritin levels.
  • If hemoglobin electrophoresis is normal and the iron panel and ferritin level are within normal limits, alpha thalassemia trait/silent carrier is the likely diagnosis. The pediatrician can counsel the family regarding alpha thalassemia trait, and there is no need to refer to a hematologist. 

Dr. Glass is a member of the AAP Section on Hematology/Oncology (SOHO). Dr. Majumdar is a member of the SOHO Executive Committee. 

Close Modal

or Create an Account

Close Modal
Close Modal