Newborn Screening for Metabolic and Sickle Cell Disorders Program

Hemoglobinopathies Overview

Hemoglobinopathies are recessively inherited abnormalities in the structure of hemoglobin. Sickle cell diseases (SS, SC, S-beta thalassemia) affect about one in 1300 Georgia infants (about one in 400 infants of African American descent).

The most clinically significant abnormal hemoglobin condition is sickle cell anemia. In this condition, the predominant hemoglobin is hemoglobin S (HbS). In the oxygenated state, HbS functions normally, but when this hemoglobin is deoxygenated, it forms crystal-like rods that deform the red blood cell into a brittle sickle shape. These malformed red blood cells are easily destroyed, causing hemolytic anemia, and tend to occlude small blood vessels causing dactylitis, stroke, pulmonary infarction, splenic sequestration, damage to internal organs, and episodes of severe pain.

Clinical Features

The affected infant appears normal at birth. Anemia develops in the first few months of life as production of fetal hemoglobin decreases and production of HbS increases. The anemia is usually mild, needing no treatment. Enlargement of the spleen is caused by trapping of sickled red cells. If this occurs acutely, severe anemia develops rapidly and transfusions are necessary. Splenic sequestration can cause death. Strokes and acute chest syndrome are also life-threatening complications that occur in childhood.

Infants and children with sickle cell anemia are particularly susceptible to infection due to Streptococcus pneumoniae, Hemophilus influenzae type b, Mycoplasma pneumoniae, Staphylococcus aureus, E. coli, and Salmonella species. Infection may manifest as pneumonia, meningitis, osteomyelitis, septicemia or other infections. Prompt antibiotic therapy can be life saving. Studies showed that prophylactic oral penicillin started early and maintained throughout childhood decreases the number of episodes of infection and deaths from infection.

Sickle cell anemia affects growth. By about four years of age, height and weight growth rates may be slowed. Chronic hemolysis causes high prevalence of gallstones. Microvascular occlusion causes retinopathy, nephropathy, leg ulcers and myocardial dysfunction.

Variants and other clinically significant hemoglobinopathies identified by newborn screening

Clinically significant sickling disease also results when one of the beta globin genes produces hemoglobin S and the other four beta gene codes for hemoglobin C, D, E, or beta thalassemia: Hb SC, Hb SD, Hb SE, Hb S beta thalassemia.

Thalassemias are anemias caused by decreased synthesis of normal globin chains and therefore decreased production of hemoglobin A. Beta thalassemia genes may interact with genes for structurally abnormal hemoglobins to cause serious hemoglobinopathies.

Carrier Conditions ("Traits")

Individuals with one abnormal hemoglobin chain and one normal hemoglobin chain (heterozygotes) are carriers - often referred to as "trait". An inconclusive report refers to the possibility of transfusion interference or presence of other structurally similar hemoglobin. Most hemoglobin carriers have few or no clinical symptoms. Carrier detection provides the opportunity to educate families, to test other family members and to offer genetic counseling to those with positive results.

Laboratory Tests

The initial screening will be done by isoelectric focusing (IEF). All samples with abnormal initial screens will be retested and run through high-pressure liquid chromatograph (HPLC). All sickle cell cases will be identified by citrate agar electrophoresis (CAE) as well. It is expected that very low concentrations (less than 1% of the total hemoglobin) of HBS or HBC, especially in premature infants, may escape detection by IEF. Health care providers should be aware of this possibility.

Confirmatory Testing

Confirmation of suspected infants with sickle cell disease will be done at the Medical College of Georgia using a second liquid blood sample.

For questions, please call (706) 721-9640.

Caution: Solubility testing (Sickle Dex®, sickle prep) Never use as a confirmatory test.

Treatment

If a neonate is identified with sickle cell disease, prophylactic penicillin should be immediately initiated. Parents need education about how to take a temperature, the care of acute illness and how to assess spleen size. Consultation with a pediatric hematologist, who is knowledgeable in the diagnosis and management of hemoglobin disorders, is advised.

In addition to routine required immunizations, infants with sickle cell disease should receive the pneumococcal polysaccharide and conjugated vaccine, the hepatitis B vaccine and the trivalent influenza virus vaccine (flu vaccine) following recommended guidelines. In addition, many physicians recommend that infants with sickle cell disease receive the meningococcal vaccine. Families with sickle cell disease or trait should be referred for education, testing, and genetic counseling.

Expected Outcome

With appropriate medical care and management, death from infection and splenic sequestration can be prevented. This has resulted in a dramatic improvement in life expectancy for infants born with sickle cell disease. Median survival is now greater than 50 years. Complications from sickle cell disease can also be better treated and prevented.

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