Hemoglobin Variants

An Overview of Hemoglobin and Newborn Screen Testing

Doctor's desk
Doctor's desk. Andrew Brookes/Creative RF/Getty Images

Hearing your child has an abnormal hemoglobin on newborn screen can be scary.  Take a deep breath and let's take a closer look at what that means for you and your child.  

Newborn screening has dramatically improved the lives of numerous children by identifying life threatening illnesses as newborns so that treatments can be started prior to complications.  This has been achieved by continuing to improve the screening tests included.

 In addition to identifying important medical conditions, sometimes, these tests identify children as carriers of conditions.  

Specific to blood disorders, newborn screening is used to identify children with sickle cell disease and thalassemia (alpha and beta). This area of the newborn screen might be labeled hemoglobinopathies, disorders of hemoglobin. Identifying these conditions allows early referral to a hematologist and the ability to start life-saving treatment prior to complications.  The testing performed, however, is not specific to just these disorders.  

What is hemoglobin?

Hemoglobin is a protein housed inside the red blood cell.  The hemoglobin carries oxygen in the red blood cell to all the tissues in the body.  When there is not enough hemoglobin present, you are labeled as having anemia.  There are two broad types of disorders of hemoglobin.  Hemoglobinopathies are disorders due to structural changes in the hemoglobin.

 Sickle cell disease is the most common hemoglobinopathy.  There is also thalassemia, disorders due to dysfunctional production of hemoglobin.  The two most common of these are alpha thalassemia and beta thalassemia.

What does the newborn screen look for?

Shortly after birth, infants should make two types of hemoglobin, hemoglobin F (fetal) and hemoglobin A (adult).

 At birth, the body should be making more hemoglobin F than hemoglobin A.  On newborn screen of a baby without hemoglobinopathy, the result will read FA indicating only these two hemoglobins were noted.  Results other than FA are considered abnormal but does not mean your baby has a hemoglobinopathy.  The newborn screen can also identify carriers of these disorders, also called trait status.  

What are the possible results for newborn screening?

There are a long list of possibilities.  The most common ones are listed below grouped by hemoglobin affected.  

Hemoglobin S (sickle hemoglobin)

  • FAS indicates sickle cell trait. 
  • FS indicates sickle cell disease, either hemoglobin SS or sickle beta zero thalassemia.
  • FSA indicates sickle beta plus thalassemia, a generally milder form of sickle cell disease.
  • FSC indicates a type of sickle cell disease called hemoglobin SC.

Hemoglobin C - Hemoglobin C appears to have originated in West Africa.

  • FAC indicates hemoglobin C trait or carrier.
  • FC indicates hemoglobin CC disease or hemoglobin C beta zero thalassemia.  This generally causes a mild to moderate anemia that is well tolerated.
  • FCA indicates hemoglobin C beta plus thalassemia.  This may cause a mild anemia.

Hemoglobin E - Hemoglobin E is most common in Southeast Asia 

  • FAE indicates hemoglobin E trait or carrier.
  • FE indicates hemoglobin EE disease or hemoglobin E beta zero thalassemia.  Hemoglobin EE is very mild with little to no anemia.  The red blood cells in hemoglobin EE are very small (low MCV).  Hemoglobin E beta zero thalassemia can vary greatly from moderate anemia to transfusion dependent anemia.  Because of the large difference between these two disorders your child will likely see a hematologist to determine the final diagnosis.
  • FEA indicates hemoglobin E beta plus thalassemia.  This condition can vary greatly.  Your child will likely be referred to a hematologist for further work-up.

Other hemoglobin variants

  • FAOther indicates a hemoglobin variant trait.  There are over 1000 hemoglobin variants and very few of them cause any issues.  Most of them are small structural changes that do not affect the hemoglobin's function.  In this circumstance, it is generally recommended to obtain additional lab work after 6 months of age to determine if this hemoglobin variant is going to be a problem.  Hemoglobin variants are named for the location they were first described.  Examples include hemoglobin Austin, hemoglobin New York, and hemoglobin Philly.

Thalassemia

  • F only indicates the presence of beta thalassemia, likely major.
  • FABarts generally indicates alpha thalassemia trait, a carrier state.  Some babies with alpha thalassemia trait will not be identified on newborn screen and may be diagnosed later in life.  
  • FA + elevated Barts generally indicates Hemoglobin H disease, a form of alpha thalassemia.  

This is not a complete list as there are numerous possible results on newborn screen testing.  If you have questions or concerns about your child's newborn screen result, contact your child's pediatrician.  

Continue Reading