Thalassaemias: β and α
- Lesion
Too few globin chains of one kind: cells are small and pale, the unpaired chains clump and kill precursors, and iron builds up.
What it is
The thalassaemias are inherited disorders in which synthesis of α- or β-globin chains is reduced or absent. Beta-thalassaemia is usually caused by point mutations (splicing, promoter, chain-terminating) and alpha-thalassaemia by gene deletions. The missing chain causes underhaemoglobinized microcytic cells; the surplus chain is the real culprit. In β-thalassaemia free α chains precipitate and kill erythroid precursors in the marrow (ineffective erythropoiesis), which drives marrow expansion, extramedullary haematopoiesis and excessive iron absorption through suppression of hepcidin.
Structure
- Smear: microcytosis, hypochromia, marked anisopoikilocytosis, target cells, basophilic stippling, nucleated red cells.
- Marrow: striking erythroid hyperplasia with dying precursors.
- Bone: expanded marrow erodes cortex; new bone forms perpendicular spicules (crew-cut on radiograph).
- Organs: haemosiderosis and secondary haemochromatosis in liver, heart and endocrine glands; spleen enlarged by extramedullary haematopoiesis.
Step by step
- Mutations reduce β-globin (β+) or abolish it (β0); deletions remove α-globin genes.
- Less HbA forms: small, pale cells.
- Unpaired α chains precipitate in precursors, damaging membranes: most die in the marrow.
- Severe anaemia raises erythropoietin; the marrow expands and haematopoiesis spreads to spleen and liver.
- Erythroid precursors release erythroferrone, which suppresses hepcidin: gut iron absorption rises.
- Iron from absorption and transfusions deposits in heart, liver and glands.
Thalassaemia syndromes
| Syndrome | Genotype | Clinical picture | Haemoglobin findings |
|---|---|---|---|
| β-thalassaemia major | Two defective β alleles (β0 or β+) | Severe anaemia from infancy, transfusion-dependent | Mostly HbF; little or no HbA |
| β-thalassaemia minor (trait) | One defective β allele | Mild microcytic anaemia, often none | HbA2 raised |
| Silent carrier | One α gene deleted | None | Normal or slight microcytosis |
| α-thalassaemia trait | Two α genes deleted (same or opposite chromosomes) | Mild microcytic anaemia | Normal HbA2; Hb Bart at birth |
| HbH disease | Three α genes deleted | Moderate haemolytic anaemia | HbH (β4) inclusions |
| Hb Bart hydrops fetalis | Four α genes deleted | Fetal death or severe hydrops | Hb Bart (γ4) with very high oxygen affinity |
Markers
- HbA2
- HbF
- HbH inclusions
- Ferritin
Clinical notes
- Trait vs iron deficiency: thalassaemia trait has a normal or high red cell count, normal ferritin and raised HbA2 (in β-trait).
- Chelation prevents cardiac death; stem cell transplantation and gene therapy can cure β-thalassaemia major.
Test yourself
Think of the answer, then tap the question to see it.
Why is erythropoiesis ineffective in β-thalassaemia major?
Excess unpaired α chains precipitate in erythroid precursors, damaging membranes so most die in the marrow.
Which haemoglobin is raised in β-thalassaemia trait?
HbA2 (α2δ2).
Why do patients absorb too much iron?
Expanded erythroid precursors release erythroferrone, which suppresses hepcidin and increases gut iron uptake.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Beta thalassemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Alpha thalassemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.