betathalassemia

Beta-thalassemia is an inherited blood disorder caused by mutations in the HBB gene that reduce or abolish the production of beta-globin chains, a component of hemoglobin. It is inherited in an autosomal recessive pattern, so affected individuals usually have two defective copies, while carriers have one defective copy and typically show no or mild symptoms.

The condition has a clinical spectrum that includes beta-thalassemia major (Cooley’s anemia), intermedia, and minor (trait). Major form usually becomes symptomatic in early childhood with severe anemia, pallor, fatigue, jaundice, bone changes of the face and skull, splenomegaly, and growth delays. Intermedia forms present with moderate anemia, while trait individuals are typically asymptomatic or have mild microcytosis.

Pathophysiology involves reduced beta-globin synthesis leading to an imbalance with alpha-globin chains, causing ineffective erythropoiesis and hemolysis. Accumulation of unpaired alpha chains damages red blood cells, contributing to a chronic anemia and related complications.

Diagnosis is based on blood tests and genetic confirmation. Complete blood count typically shows microcytic, hypochromic anemia. Hemoglobin electrophoresis reveals low or absent HbA and increased HbA2 and HbF; genetic testing confirms the specific mutations. Prenatal diagnosis and newborn screening are available in many regions.

Management for major disease centers on regular transfusions to maintain adequate hemoglobin levels and iron chelation therapy to prevent iron overload (options include deferoxamine, deferasirox, and deferiprone). Supportive care includes folic acid, vaccination against encapsulated bacteria, and surveillance for organ complications. Splenectomy may be considered in selected cases. Curative options are allogeneic hematopoietic stem cell transplantation in appropriate patients, with gene therapy approaches under investigation.

Prognosis has improved with modern care, but iron overload remains a key challenge. Genetic counseling, carrier screening, and prenatal testing are important for family planning. Global prevalence is higher in the Mediterranean, Middle East, South Asia, and parts of Africa, reflecting historical selective pressures and population genetics.