Hands (A) and feet (B) of a child with hand-foot syndrome showing marked periosteal reaction and diffuse osteolysis and osteosclerosis. Sickle cell anemia (SCA) is the most common single-gene disorder in African Americans, affecting approximately 1 in 375 African Americans in the United States. It was first described in a 20-year-old dental student from Grenada in 1910, and Dr. Linus Pauling described the gene encoding of the disease in 1949. The major clinical manifestations of the disease include the five INs: insufficient ossification (marrow hyperplasia), infarction, infection, in failure (because of the anemia), and involution (of the spleen). A common clinical presentation of vascular occlusion in SCA is hand-foot syndrome (sickle cell dactylitis), which most commonly occurs between the ages of 6 months and 2 years. Imaging findings, best appreciated on radiography, include soft tissue swelling, symmetric mixed osteosclerosis, and osteolysis of the shafts of the involved bones with diffuse periostitis. Epiphyseal infarction and osteonecrosis, most commonly of the femoral head, may be seen in any patient with SCA. Other manifestations of infarction include the bone-within-a-bone appearance and medullary infarction of long bones, H-shaped or Lincoln-log vertebral bodies, and the “snow-capping” appearance of the humeral head. Infection is 100 times more likely to occur in patients with SCA than in the normal population. The most common organism overall is Staphylococcus aureus. However, SCA patients are susceptible to Salmonella and other enteric organisms because of bowel ischemia and also to encapsulated organisms because of their splenic autoinfarction. The differential diagnosis of SCA includes sickle cell thalassemia and thalassemia. Hip findingsSickle cell anemia (SCA)differential diagnosis of may mimic Legg-Calvé-Perthes diseaseLegg-Calvé-Perthes disease, and on occasion, the vertebral findings may resemble the biconcave appearance of osteoporosis. The current major therapies for SCA are geared toward replacing the lost hemoglobin (Hb) SS cells by transfusion or by decreasing the number of Hb S cells that are produced.