Complexity of alpha thalassemia: growing health problem with new approaches to screening, diagnosis, and therapy

Alpha thalassemia, the most common genetic disorder of hemoglobin synthesis, affects up to 5% of the world's population. It represents a group of conditions with reduced or absent synthesis of one to all four of alpha globin genes. Deletional or nondeletional mutations occur on chromosome 16. Its severity ranges from asymptomatic to fatal in utero. Hemoglobin H disease, a mutation of three alpha globin genes, is more severe than previously recognized. Anemia, hypersplenism, hemosiderosis, growth failure, and osteoporosis are commonly noted as the patient ages. Alpha thalassemia major, a usually fatal in utero disease, is now recognized to have a complex molecular and phenotypic expression with increasing births being reported. Surviving newborns without intrauterine transfusion often have congenital anomalies and neurocognitive injury. Serious maternal complications often accompany pregnancy. Doppler ultrasonography with intrauterine transfusion ameliorates these complications. The high incidence in many populations mandates population screening and prenatal diagnosis of at-risk couples. Universal newborn screening has been adopted in several regions with DNA confirmatory testing. These advances have resulted in ethical dilemmas for the family and the provider.