Beta thalassemia major (Cooley's anemia) is an autosomal recessive hereditary disease characterized by absent (β0) or greatly reduced (β+) beta globin chain synthesis due to homozygous or compound heterozygous mutations in the beta globin gene. High prevalence is seen in the Mediterranean basin, Middle East, Southeast Asia and Africa; in Turkey it is particularly frequent in the Aegean, Marmara and Southeast regions. Carrier frequency in Turkey is approximately 2-3%. The disease was described in 1925 by Cooley.
Pathophysiologically, insufficient beta globin production leads to excess alpha globin chains; these accumulate in red cell precursors causing ineffective erythropoiesis (premature cell death in bone marrow) and peripheral hemolysis. As a result severe microcytic hypochromic anemia develops. To compensate for chronic anemia the bone marrow expands, causing bone deformities (chipmunk facies, bone thinning), and extramedullary hematopoiesis leads to organomegaly (hepatosplenomegaly). Chronic transfusion need and increased gastrointestinal iron absorption cause iron overload (secondary hemochromatosis); untreated, cardiomyopathy, endocrine disorders (hypogonadism, diabetes, hypothyroidism, hypoparathyroidism) and liver disease develop, leading to early death.
Diagnosis usually begins between 6-24 months with severe anemia. CBC (severe microcytic hypochromic anemia, Hb usually <7 g/dL), peripheral smear (target cells, basophilic stippling, nucleated RBCs), and hemoglobin electrophoresis/HPLC (decreased/absent HbA, markedly increased HbF 70-90%) are diagnostic. Genetic testing confirms beta globin gene mutations. Treatment includes regular transfusion every 3-4 weeks (target pre-transfusion Hb 9-10.5 g/dL), iron chelation (deferoxamine, deferasirox, deferiprone), allogeneic stem cell transplantation (curative in matched sibling donors), and recently approved gene therapy (betibeglogene autotemcel) and luspatercept.