Alpha-thalassemia and related disorders

Alpha-thalassemia and related disorders (Orphanet code 275745) encompass a group of inherited hemoglobin disorders caused by reduced or absent production of alpha-globin chains, which are essential components of normal hemoglobin. The alpha-globin genes (HBA1 and HBA2) are located on chromosome 16, and humans normally carry four copies (two on each chromosome). The clinical severity of alpha-thalassemia depends on how many of these four alpha-globin genes are deleted or dysfunctional, ranging from a clinically silent carrier state (one gene affected) to the lethal condition known as hemoglobin Bart hydrops fetalis syndrome (all four genes affected). The spectrum of alpha-thalassemia includes several recognized clinical forms. Silent carriers (one gene deletion) are asymptomatic with minimal or no hematologic abnormalities. Alpha-thalassemia trait (two gene deletions) causes mild microcytic hypochromic anemia. Hemoglobin H (HbH) disease (three gene deletions) presents with moderate to moderately severe hemolytic anemia, splenomegaly, jaundice, and characteristic HbH inclusions in red blood cells. Hemoglobin Bart hydrops fetalis syndrome (four gene deletions) is the most severe form, typically resulting in fetal death or neonatal death due to severe anemia, generalized edema (hydrops fetalis), and heart failure. Related disorders include hemoglobin Constant Spring and other non-deletional alpha-thalassemia variants, as well as alpha-thalassemia associated with intellectual disability (ATR-X syndrome and ATR-16 syndrome). Alpha-thalassemia primarily affects the hematologic system but can have multisystem consequences in severe forms, including hepatosplenomegaly, skeletal changes from extramedullary hematopoiesis, gallstones, and growth retardation. The condition is most prevalent in Southeast Asian, Mediterranean, Middle Eastern, African, and South Asian populations. Treatment varies by severity: silent carriers and those with alpha-thalassemia trait generally require no treatment. HbH disease management includes folic acid supplementation, avoidance of oxidant drugs, monitoring for complications, and occasional blood transfusions during hemolytic crises or infections. Splenectomy may be considered in severe cases. For hemoglobin Bart hydrops fetalis, intrauterine transfusions and chronic transfusion therapy after birth have allowed survival in some cases, though these individuals require lifelong transfusion support and iron chelation therapy. Hematopoietic stem cell transplantation is a potential curative option for severe forms. Genetic counseling is essential, particularly for at-risk couples.

Common questions about Alpha-thalassemia and related disorders