Conditions · Metabolism: heme, bilirubin and iron
Thalassemias (α and β) !
Inherited diseases in which too little α or β globin is made; red cells come out small and few, from almost no symptoms to severe anemia.
Updated 2026-11-01
Structures involved
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In biochemistry
- Chromatography
- Iron metabolism
- Hemoglobin variants (HbA, HbA2, HbF, HbS, HbC)
- RNA processing (cap, poly-A tail and splicing)
- Types of mutations
- Gene therapy
- CRISPR-Cas9 and genome editing
- Spliceosome
- Oxygen binding: haemoglobin versus myoglobin
In immunology
In histology
In the clinical exam
In physiology
Why it happens
- Pigments in tissue: lipofuscin, hemosiderin, melanin, bilirubin, carbon
- Fetal hydrops: immune and nonimmune
What it is
Quantitative hemoglobinopathies from reduced synthesis of α chains (HBA1/HBA2 genes, usually deletions) or β chains (HBB gene, usually point mutations). Autosomal recessive inheritance.
Who gets it
Very common around the Mediterranean, the Middle East, South Asia and Africa. In Colombia they are found mainly in people with African or Mediterranean ancestry, especially on the Caribbean coast; the trait is often mistaken for iron deficiency.
Causes
- α-thalassemia: loss of 1 to 4 of the α genes
- β-thalassemia: mutations that reduce (β⁺) or abolish (β⁰) the β chain
Risk factors
- Carrier parents
- Mediterranean, African, Asian or Middle Eastern ancestry
Pathophysiology
One chain is missing and the other is left over. In β-thalassemia free α chains precipitate inside precursors and destroy them in the marrow (ineffective erythropoiesis) and spleen (hemolysis). The marrow expands (skull and facial bones), liver and spleen resume blood formation, and erythroferrone lowers hepcidin: extra iron is absorbed on top of transfused iron. In α-thalassemia γ chains (Hb Bart's) or β chains (HbH) are left over and do not deliver oxygen.
Classification
- α: silent carrier (1 gene), trait (2), HbH disease (3), Hb Bart's hydrops fetalis (4)
- β: minor or trait (one allele), intermedia (non-transfusion-dependent) and major or Cooley (transfusion-dependent)
Symptoms and signs
- Trait: no symptoms or mild anemia with small red cells
- Major: pallor, irritability and poor growth between 6 and 24 months
- Large abdomen from an enlarged liver and spleen
- Prominent forehead and enlarged upper jaw
- Jaundice
Diagnosis
- Clinical
- Microcytic anemia that does not respond to iron, with a family history or at-risk ancestry.
- Tests
- Blood count: marked microcytosis with normal or high red-cell count (Mentzer index below 13); smear with target cells; normal ferritin; electrophoresis or HPLC: HbA2 above 3.5 % in β-thalassemia minor, high HbF in the major form; HbH inclusions; molecular testing (essential in α-thalassemia).
- Imaging
- Skull X-ray with a «hair-on-end» appearance in the major form; T2* MRI for liver and heart iron; abdominal ultrasound for the spleen.
Treatment
- Conservative
- Trait: no treatment needed; avoiding unnecessary iron and offering genetic counselling
- Procedure
- Regular transfusions in the major form to maintain hemoglobin and suppress the marrow
- Medical
- Iron chelation (deferoxamine, deferasirox, deferiprone) and folic acid
- Medical
- Luspatercept, which improves erythroid maturation and reduces transfusions in adults
- Surgical
- Splenectomy for hypersplenism with high transfusion needs
- Procedure
- Hematopoietic stem cell transplantation (curative) and gene therapies in specialised centres
Drugs for this condition
Complications
- Iron overload: cardiomyopathy, cirrhosis, diabetes, hypogonadism
- Bone deformities and osteoporosis
- Gallstones
- Thrombosis and infections after splenectomy
Prognosis
The trait carries a normal life; in the major form, adequate chelation has extended survival into later adulthood.
Prevention
- Carrier screening and prenatal diagnosis
Test yourself
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How is thalassemia trait distinguished from iron deficiency on a blood count?
In the trait microcytosis is marked with a normal or high red-cell count (Mentzer below 13) and normal ferritin.
Which hemoglobin fraction confirms β-thalassemia minor?
HbA2 above 3.5 %.
Why does β-thalassemia major appear after 6 months of age?
Before then HbF (α₂γ₂), which needs no β chains, predominates.
Which tetramer forms when all four α genes are missing?
Hb Bart's (γ₄), which does not release oxygen and causes hydrops fetalis.
Related conditions
- Hereditary hemochromatosis
- Sickle cell disease
- Iron deficiency anaemia
- Gallstones (cholelithiasis)
- Heart failure
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Beta thalassemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Alpha thalassemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Thalassemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Thalassemia | Beta Thalassemia | MedlinePlus (MedlinePlus, US National Library of Medicine, 2026).
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