Genetic Disorders
Thalassemia
지중해빈혈
Microcytic anemia from defective α/β-globin chain synthesis
- How common
- Common in Mediterranean, SE Asian populations
- Typical age
- Infant/child onset (severe forms)
What is it?
Mutations in α-globin (HBA1/2, chr 16) or β-globin (HBB, chr 11) → chain imbalance → ineffective erythropoiesis + hemolysis.
Commonly affected: RBCs, marrow, spleen, liver, heart (iron overload)
How it develops
- Globin gene mutationα-thal: deletions; β-thal: point mutations
- Chain imbalanceExcess chains damage RBCs
- Ineffective erythropoiesis + hemolysisMarrow hyperplasia, splenomegaly
- Iron overload + bone deformityTransfusion dependence, bone changes ("crew cut")
Symptoms
- Severe microcytic anemiaHb 3–7 g/dL (severe)
- Iron overloadHeart failure, cirrhosis, endocrinopathies
- HepatosplenomegalyExtramedullary hematopoiesis
- Bone deformityExpanded marrow cavity
- Growth retardationChronic anemia causes delay
How it is examined
- Peripheral smearMicrocytic, target cells, basophilic stippling
- Hb electrophoresisβ-thal: HbA2, HbF↑; α-thal: HbH
- Genetic testingConfirm HBA1/2 deletions or HBB point mutations
Imaging
Skull XR: "crew cut" (radial striations). Chest: cardiomegaly.
- "Crew cut" skull
- Cardiomegaly
Cardiac T2* MRI for iron overload (LIC).
- Cardiac iron deposition
- Hepatic iron content↑
Non-surgical care
- Regular transfusionEvery 3–4 wks (maintain Hb >9)
- Iron chelationDeferasirox (PO), deferoxamine (SC)
- FolateChronic hemolysis increases need
- Luspatercept (β-thal)TGF-β superfamily ligand trap
Conservative options are generally tried first. Medications listed here can have side effects — discuss them with your prescriber.
When surgery is considered
Refractory or curative intent
Procedures that may be discussed
- HSCT - curative
- Gene therapy (beti-cel for β-thal)
- Splenectomy (reduces transfusion needs)
Outlook
With transfusion + chelation, survival >50 years. HSCT/gene therapy curative.