Alpha-thalassemia

Alpha-thalassemia is an inherited hemoglobin disorder characterized by reduced or absent production of alpha-globin chains, which are essential components of normal hemoglobin. It is caused by deletions or, less commonly, point mutations in the HBA1 and HBA2 genes located on chromosome 16. Because there are four alpha-globin gene copies (two on each chromosome 16), the clinical severity of alpha-thalassemia depends on how many genes are affected. The disease primarily affects the hematologic system but can have widespread consequences on multiple organ systems due to chronic anemia and ineffective erythropoiesis. The clinical spectrum ranges from a silent carrier state (one gene deleted, clinically asymptomatic) to alpha-thalassemia trait (two genes deleted, mild microcytic anemia), hemoglobin H (HbH) disease (three genes deleted, moderate to severe hemolytic anemia with splenomegaly, jaundice, and fatigue), and hemoglobin Bart's hydrops fetalis syndrome (all four genes deleted, the most severe form, which is usually fatal in utero or shortly after birth without intervention). HbH disease may also be caused by non-deletional mutations, which tend to produce a more severe phenotype. Patients with HbH disease can experience worsening anemia during infections, pregnancy, or exposure to oxidant drugs. Alpha-thalassemia is most prevalent in Southeast Asia, southern China, the Mediterranean region, the Middle East, and sub-Saharan Africa. Treatment depends on clinical severity. Silent carriers and those with alpha-thalassemia trait generally require no treatment. Patients with HbH disease may need intermittent or regular red blood cell transfusions, folic acid supplementation, and monitoring for iron overload, which may require iron chelation therapy. Splenectomy may be considered in cases of significant hypersplenism. For Bart's hydrops fetalis, intrauterine transfusions and early postnatal management have allowed survival in some cases, though affected individuals require lifelong transfusion therapy. Hematopoietic stem cell transplantation is a potentially curative option for severe forms, and gene therapy approaches are under investigation.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Alpha-thalassemia