Pathophysiology
Alpha: 1-4 gene deletions (silent, minor, HbH, hydrops fetalis Barts). Beta: point mutations causing beta-thal minor, intermedia or major (Cooley anaemia) with ineffective erythropoiesis.
Sources: BSH Beta-Thal 2016; Beti-cel (NEJM 2022;386:415)
Presentation
Beta-thal major: severe anaemia by 6 months, hepatosplenomegaly, skeletal deformities (chipmunk facies), extramedullary haematopoiesis, iron overload from transfusions.
Diagnosis
CBC (microcytosis with normal RDW and near-normal ferritin), Hb electrophoresis (HbA2 elevated in beta-thal trait; HbH bands in HbH disease); molecular studies for alpha deletions.
Management
Beta-thal major: chronic transfusion + iron chelation (deferasirox, deferiprone). Splenectomy sometimes required. Curative options: allogeneic HSCT; gene therapy (betibeglogene autotemcel, exa-cel) for transfusion-dependent beta-thal.
