Review Question - QID 106635

This child is presenting with findings classic for sickle cell crisis. Sickle cell anemia is caused by a valine substitution for glutamic acid in the 6th position of the ß-globin chain of hemoglobin.

Sickle cell anemia is an autosomal recessive disorder due to a mutation in the hemoglobin ß-chain. Patients frequently present with acute vaso-occlusive episodes. Acute vaso-occlusive sickling episodes are often precipitated by infection, acidosis, hypoxia, or dehydration. Vaso-occlusive crises can present in a variety of ways, including chest pain, bone pain, fever, stroke, priapism, abdominal pain, and dactylitis (Figure A).

Dhaliwal and Cornett discuss sickle cell anemia. Sickle cell anemia is an inherited disorder caused by a point mutation of glutamic acid to valine at position 6 of the hemoglobin ß-chain. The mutated hemoglobin (Hgb S) tetramers polymerize causing sickling of deoxygenated RBCs. Membrane abnormalities from sickling, as well as oxidative damage caused by Hgb S, lead to splenic sequestration of RBCs. Additionally, some degree of intravascular hemolysis occurs. To aid in diagnosis, hemoglobin electrophoresis can be used, which reveals a predominance of hemoglobin S. Additionally, characteristic sickle cells are observed on the peripheral smear (seen in Figure B).

Manwani and Frenette discuss treatment for sickle cell anemia. Hydroxyurea has emerged as an important treatment to prevent acute sickle cell crises. Hydroxyurea is a potent inducer of fetal hemoglobin (HbF). There are multiple mechanisms by which hydroxyurea induces HbF production. While there are few children who do not respond to treatment, up to one-third of adults are non-responders. The medication has high efficacy in those who respond to treatment. Unfortunately, myelosuppression is a dose-limiting side effect.

Figure A shows dactylitis, a common presentation in children affected by sickle cell anemia. Figure B shows sickled RBCs. Illustration A demonstrates the pathological mechanism behind sickle cell disease.

Incorrect Answers:
Answer 1: Tri-nucleotide repeat amplification is not involved in sickle cell disease.
Answer 2: Mutations in the gene coding for the alpha subunit are responsible for alpha-thalassemia, not sickle cell disease.
Answer 4: Increased HbF is not causative of sickle cell disease. In fact, increased HbF is desirable, as it reduces sickling. This is the intended effect of hydroxyurea, as discussed above.
Answer 5: Reduced levels of folic acid do not cause sickle cell disease.