- Kwesi Sackey, MD*
- *Associate Professor of Pediatrics, Division of Hematology/Oncology, The University of Texas Medical Branch, Galveston, TX.
Upon completion of this article, readers should be able to:
Describe the infections to which children who have sickle cell disease are susceptible.
Describe the complications of sickle cell disease.
Describe the presentation of thalassemia major.
Sickle Cell Disease
Sickle cell disease is a hemoglobinopathy characterized by the inheritance of two abnormal hemoglobin genes, at least one of which is the sickle hemoglobin gene. The most common types are: hemoglobin SS disease, hemoglobin SC disease, and hemoglobin S-thalassemia. The inheritance of one normal hemoglobin gene (A) in association with hemoglobin S leads to the formation of hemoglobin AS, which also is called sickle trait and is considered a carrier state, not a “disease.”
The sickle gene is prevalent in West Africa, Central Africa, the Mediterranean, the Middle East, and certain parts of India. It also is present in other parts of the world where black immigrants from Africa comprise a substantial portion of the population. In the United States, the incidence of the sickle gene among African Americans is 8%.
PATHOLOGY, PATHOPHYSIOLOGY, AND PATHOGENESIS
In the sickle hemoglobin, a mutation in codon 6 of the beta chain (GAT8594’3fGGT) leads to replacement of glutamic acid by valine. This hemoglobin undergoes changes precipitated by many factors, with the classic one being deoxygenation. Deoxygenation is associated with the formation of crystals of less soluble hemoglobin S that align in a unique fashion, leading to the unusual shape of the cell. Other precipitating factors include pH changes and temperature. The rigid cells, in combination with the attendant increase in viscosity, result in sludging and organ infarction.
The clinical manifestations of sickle cell disease vary from patient to patient and from region to region, even among those who have apparently similar phenotypes. The variation ranges from a complete lack of symptoms even into adulthood to life-threatening complications beginning in early infancy. Most …