Hemoglobin H disease: not necessarily a benign disorder

Hb H disease is a form of α-thalassemia often manifested clinically as thalassemia intermedia with moderate anemia. It is commonly found in Southeast Asian, Middle Eastern, and Mediterranean populations. There is a wide spectrum of genotypes and phenotypic presentations. These range from those who appear clinically to be asymptomatic, to others who are more anemic, having significant hepatosplenomegaly and requiring occasional or even regular transfusions, to the severe Hb H hydrops fetalis syndrome that can cause death in the affected fetuses late in gestation. This hereditary disorder is usually caused by deletions removing all but one single α-globin gene (deletional Hb H disease). A small proportion of patients have deletions removing 2 α-globin genes plus a nondeletional mutation affecting a third α-globin gene (nondeletional Hb H disease). In general, nondeletional Hb H disease has a more severe clinical course than the deletional form. Review of recent literature suggests that Hb H disease is not as benign a disorder as previously thought. It can bring about growth retardation during childhood and iron overload in adults regardless of previous transfusion history, leading to hepatic, cardiac, and endocrine dysfunction. Significant anemia might occur during infections, fever, hypersplenism, or pregnancy that may necessitate the need for blood transfusions. An essential part of the maternal/child health care should include screening the partners of all pregnant women with Hb H disease for their thalassemia carrier status, and providing these and other couples who are at risk of conceiving offspring with Hb H disease with appropriate genetic counseling. Prospective and systematic studies of the natural history of Hb H disease, particularly during infancy and childhood, as well as during pregnancy, have not been carried out and are much needed. Information derived from these investigations can lead to better insight to potential risk factors associated with severe disease and can help to formulate future medical interventions and treatment strategies.