A 5-year-old boy is brought to the office by his parents to establish medical care. The family recently immigrated to the United States from Nigeria. Both parents have sickle cell trait, and the patient was diagnosed with homozygous sickle cell disease (HbSS) at the age of 6 months. He has had several prior vasoocclusive crises and takes folic acid and hydroxyurea. Physical examination shows no abnormalities. Hemoglobin electrophoresis in this patient is most likely to reveal which of the following predominant hemoglobin patterns?
Electrophoresis patterns in sickle cell syndromes | |||||
HbA | HbA2 | HbF | HbS | HbC | |
Normal | ++++ | + | + | None | None |
Sickle cell trait | +++ | + | + | +++ | None |
Sickle cell anemia (SCA) | None | + | + | ++++ | None |
SCA on hydroxyurea | None | + | ++ | +++ | None |
Hemoglobin SC disease | None | + | + | +++ | +++ |
In healthy children and adults, the predominant hemoglobin is hemoglobin A (HbA), which contains a pair of alpha and beta globins. However, small quantities of other hemoglobin types are also present; these include hemoglobin A2 (HbA2), which contains a pair of alpha and delta globins, and hemoglobin F (HbF), which contains a pair of alpha and gamma globins.
In homozygous sickle cell disease (sickle cell anemia), there are point mutations in both beta globin genes that substitute valine for glutamate at position 6. This generates a new type of hemoglobin called hemoglobin S (HbS), which is composed of a pair of alpha and a pair of beta sickle globins. HbS polymerizes when deoxygenated, reducing erythrocyte deformability and promoting painful vasoocclusion and chronic hemolysis.
Because patients with sickle cell anemia have mutations in both beta globin genes, they are unable to produce HbA (Choices B, C, and D). However, forms of normal hemoglobin that do not contain beta globin (eg, HbF, HbA2) are present at normal or mildly increased levels. Raising the concentration of these normal hemoglobins is particularly helpful because it dilutes HbS, preventing it from polymerizing. Therefore, hydroxyurea, which increases HbF production, is often administered to limit symptoms and complications of the disease.
(Choice E) Patients with hemoglobin SC disease have 1 beta globin with the sickle mutation and 1 beta globin with a mutation that substitutes lysine for glutamate at position 6. They produce two predominant hemoglobins: HbS and Hemoglobin C, the latter of which is not seen in sickle cell anemia as there is no hemoglobin C mutation.
Educational objective:
Homozygous sickle cell disease is marked by a point mutation in both beta globin genes. This leads to the generation of a new predominant hemoglobin called hemoglobin S (HbS), which polymerizes when deoxygenated. Because hemoglobin F (HbF) prevents HbS polymerization, hydroxyurea is often administered to increase HbF levels and reduce complications of the disease.