Paeds · haematology-oncology-and-transfusion

Thalassaemia syndromes

Also known as Beta-thalassaemia major · Cooley anaemia · Thalassaemia major · Alpha-thalassaemia · Haemoglobin H disease · Thalassaemia intermedia

Fellowship guide to the thalassaemia syndromes in children, the inherited disorders of globin-chain synthesis that range from the transfusion-dependent beta-thalassaemia major of early childhood to the lethal Hb Bart hydrops fetalis of four-gene alpha-thalassaemia. Covers the pathophysiology of unbalanced globin production, ineffective erythropoiesis and chronic haemolysis, the diagnosis by haemoglobin electrophoresis or high-performance liquid chromatography with a raised haemoglobin F, and the three pillars of major-disease care: regular leucodepleted transfusion keeping the pre-transfusion haemoglobin at 90 to 100 g per litre every two to five weeks, iron chelation with deferasirox started at 20 mg per kg per day once the ferritin exceeds 1000 micrograms per litre, and curative haematopoietic stem cell transplant or betibeglogene autotemcel gene therapy. Includes the alpha-thalassaemia gene-deletion ladder, transfusional iron overload monitored by cardiac T2 star magnetic resonance imaging, the luspatercept BELIEVE trial, and the alpha-thalassaemia, HbE beta-thalassaemia and thalassaemia intermedia subtypes.

high12 referencesUpdated 16 July 202628 min readVerification in progress

Practise this topic

On this page & tools

Your progress

Saved locally on this device.

Practise this topic

Target exams

RACP DWERACP DCEMRCPCH TheoryMRCPCH ClinicalABP General Pediatrics

Red flags

A child with beta-thalassaemia major presenting at six to twelve months with severe microcytic anaemia, failure to thrive and hepatosplenomegaly as the fetal haemoglobin falls needs urgent confirmation by haemoglobin separation and commencement of a regular transfusion programmeA falling cardiac T2 star of under 10 milliseconds on magnetic resonance imaging marks severe myocardial iron loading and a high short-term risk of heart failure, the leading cause of death in thalassaemia majorA child on deferiprone who develops fever and a neutrophil count under 0.5 times ten to the nine per litre has drug-induced agranulocytosis, an emergency that demands immediate cessation of the drug and broad-spectrum antibioticsA four-gene alpha-thalassaemia deletion produces Hb Bart hydrops fetalis, a condition incompatible with postnatal life without intrauterine transfusion, and a leading cause of perinatal mortality in South-East AsiaA transfusion-dependent adolescent who is short, delayed in puberty and glucose intolerant has endocrine iron overload of the anterior pituitary and pancreas, and needs hormone and endocrine surveillance

Life stages

fetalneonateinfanttoddlerpreschoolschool-ageadolescentyoung-adult-transition

Care settings

preventive-medical-homeoutpatientwarded-acutenicutelehealthrural-remote

Clinical exam formats

written-only

Board mappings

Recognises beta-thalassaemia major as the autosomal recessive disorder of beta-globin synthesis presenting at six to twelve months with severe microcytic anaemia, failure to thrive and hepatosplenomegalyStates the regular transfusion target of a pre-transfusion haemoglobin of 90 to 100 g per litre and names deferasirox at 20 mg per kg per day as the first-line oral iron chelatorNames the alpha-thalassaemia gene-deletion ladder from silent carrier through trait and haemoglobin H disease to Hb Bart hydrops fetalisExplains how unbalanced alpha-chain excess causes ineffective erythropoiesis and chronic haemolysis, and how transfusional and absorbed iron loads the liver, heart and endocrine glandsCoordinates the transfusion, chelation and monitoring programme with cardiac T2 star magnetic resonance imaging, and appraises allogeneic transplant against betibeglogene gene therapyAppraises the BELIEVE luspatercept trial and the deferasirox and deferoxamine chelation evidence of Cappellini, Piga, Borgna-Pignatti and ModellRegular leucodepleted transfusion keeps the pre-transfusion haemoglobin at 90 to 100 g per litre, given every two to five weeksDeferasirox starts at 20 mg per kg per day orally once daily and chelation begins once the ferritin exceeds 1000 micrograms per litreA cardiac T2 star under 10 milliseconds marks severe myocardial iron loading and a high risk of heart failureCounsels the family of a newly diagnosed infant on the inheritance, the lifelong transfusion and chelation burden, and the reproductive and curative optionsBuilds the multidisciplinary plan that runs haematology, transfusion, chelation, endocrine, cardiac and transition care togetherSynthesises the transfusion-dependent adolescent with iron overload, delayed puberty and glucose intolerance into an endocrine and chelation strategyLevel 1: Recognition of the severe microcytic anaemia of beta-thalassaemia major and initiation of the transfusion programmeLevel 2: Application of iron chelation and surveillance of iron load by ferritin and cardiac T2 star magnetic resonance imagingLevel 3: Coordination of curative therapy, endocrine and cardiac late-effects management, and transition to adult careThe genetics of the HBB and HBA gene clusters, the beta-zero and beta-plus alleles, and the four alpha-gene deletion ladderThe haemoglobin electrophoresis pattern of a raised haemoglobin F and the transfusion and chelation dosesThe T2 star thresholds, the BELIEVE luspatercept evidence, and the betibeglogene autotemcel gene therapy dataCommunication of the diagnosis, the inheritance, and the lifelong transfusion and chelation plan to the familyStructured assessment of the transfused child for growth, puberty, splenomegaly, pallor and endocrine and cardiac signsRecognition and counselling around the iron-overload and curative-therapy pathwayBeta-thalassaemia major as an autosomal recessive disorder of beta-globin synthesis diagnosed by haemoglobin electrophoresis with a raised haemoglobin FRegular transfusion, iron chelation and iron-overload monitoring as the pillars of careAllogeneic haematopoietic stem cell transplant and betibeglogene autotemcel gene therapy as the curative optionsRecognition of the six-to-twelve-month presentation of beta-thalassaemia major and the urgency of starting a transfusion programmeApplication of iron chelation and cardiac T2 star surveillance from the second year of lifeCoordination of the multidisciplinary thalassaemia team and the transition to adult careCanadian approach to carrier screening, prenatal diagnosis and newborn identification of the thalassaemia syndromesRegular transfusion, iron chelation and cardiac T2 star iron surveillanceCurative transplant and gene therapy and the long-term management of endocrine and cardiac late effects

Your progress

Saved locally on this device.

Practise this topic

Target exams

RACP DWERACP DCEMRCPCH TheoryMRCPCH ClinicalABP General Pediatrics

Red flags

Life stages

fetalneonateinfanttoddlerpreschoolschool-ageadolescentyoung-adult-transition

Care settings

preventive-medical-homeoutpatientwarded-acutenicutelehealthrural-remote

Clinical exam formats

written-only

Board mappings

Overview & Definition

A child born with thalassaemia makes haemoglobin that is structurally normal but quantitatively wrong, because one of the two globin protein chains is produced too slowly or not at all. The name covers a family of inherited anaemias in which the balance between alpha and beta globin is lost, the spare chains clump and destroy the red cell from within, and the child is left with severe, chronic, microcytic anaemia. The commonest and most severe form is beta-thalassaemia major, once called Cooley anaemia, in which the child makes little or no beta-globin and becomes dependent on lifelong blood transfusion from infancy. [12]

The thalassaemias are among the most common single-gene disorders in the world, and they cluster wherever malaria was historically intense, across the Mediterranean, the Middle East, South Asia and South-East Asia, because carrying one thalassaemia gene once protected a child against falciparum malaria. The severity spans a wide range, from the silent carrier who is never unwell, through the transfusion-dependent major, to the four-gene alpha-thalassaemia that kills the fetus in utero as Hb Bart hydrops fetalis. The paediatric fellow meets the whole spectrum, but the centre of gravity is the child with major disease whose life depends on a transfusion and chelation programme that begins in the first year. [12]

Three ideas make this topic central to the exam. The first is the molecular imbalance between the globin chains, because the unpaired alpha chains explain the ineffective erythropoiesis, the chronic haemolysis and the bone expansion that together shape the disease. The second is the transfusion programme, because a regular transfusion that keeps the pre-transfusion haemoglobin at 90 to 100 g per litre suppresses the abnormal marrow and lets the child grow. The third is iron chelation, because every transfusion loads the body with iron it cannot excrete, and the heart, the liver and the endocrine glands fail if that iron is not removed. The 2026 primer of Piel and colleagues and the landmark chelation trials together define modern care. [12][4]

Paediatrics Fellowship Pro

You have read the opening of this topic. The complete unit — every section and its primary-source references — is part of the Paediatrics Fellowship fellowship atlas.

References12Show ledger

[1]Thompson AA, Walters MC, Kwiatkowski J Gene therapy in patients with transfusion-dependent beta-thalassemia. N Engl J Med, 2018.PMID 29669226
[2]Cappellini MD, Viprakasit V, Georgiev P Long-term efficacy and safety of luspatercept for the treatment of anaemia in patients with transfusion-dependent beta-thalassaemia (BELIEVE): final results from a phase 3 randomised trial. Lancet Haematol, 2025.PMID 39947215
[3]Kwiatkowski JL, Thompson AA, Schneiderman J Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent beta-thalassemia. Blood, 2026.PMID 41525466
[4]Cappellini MD, Cohen A, Piga A A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood, 2006.PMID 16352812
[5]Piga A, Galanello R, Forni GL Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload. Haematologica, 2006.PMID 16818273
[6]Borgna-Pignatti C, Rugolotto S, De Stefano P Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica, 2004.PMID 15477202
[7]Borgna-Pignatti C, Cappellini MD, De Stefano P Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood, 2006.PMID 16373663
[8]Modell B, Khan M, Darlison M Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson, 2008.PMID 18817553
[9]Vichinsky EP Clinical manifestations of α-thalassemia. Cold Spring Harb Perspect Med, 2013.PMID 23543077
[10]Lal A, Viprakasit V, Vichinsky E Disease burden, management strategies, and unmet needs in alpha-thalassemia due to hemoglobin H disease. Am J Hematol, 2024.PMID 39037279
[11]Hoffbrand AV, Taher A, Cappellini MD How I treat transfusional iron overload. Blood, 2012.PMID 22919029
[12]Piel FB, de Montalembert M, Das R Thalassaemia. Nat Rev Dis Primers, 2026.PMID 42426018

Thalassaemia syndromes

Also known as Beta-thalassaemia major · Cooley anaemia · Thalassaemia major · Alpha-thalassaemia · Haemoglobin H disease · Thalassaemia intermedia

high12 referencesUpdated 16 July 202628 min readVerification in progress

Practise this topic

Overview & Definition

Paediatrics Fellowship Pro

You have read the opening of this topic. The complete unit — every section and its primary-source references — is part of the Paediatrics Fellowship fellowship atlas.

References12Show ledger

[1]Thompson AA, Walters MC, Kwiatkowski J Gene therapy in patients with transfusion-dependent beta-thalassemia. N Engl J Med, 2018.PMID 29669226
[2]Cappellini MD, Viprakasit V, Georgiev P Long-term efficacy and safety of luspatercept for the treatment of anaemia in patients with transfusion-dependent beta-thalassaemia (BELIEVE): final results from a phase 3 randomised trial. Lancet Haematol, 2025.PMID 39947215
[3]Kwiatkowski JL, Thompson AA, Schneiderman J Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent beta-thalassemia. Blood, 2026.PMID 41525466
[4]Cappellini MD, Cohen A, Piga A A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood, 2006.PMID 16352812
[5]Piga A, Galanello R, Forni GL Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload. Haematologica, 2006.PMID 16818273
[6]Borgna-Pignatti C, Rugolotto S, De Stefano P Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica, 2004.PMID 15477202
[7]Borgna-Pignatti C, Cappellini MD, De Stefano P Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood, 2006.PMID 16373663
[8]Modell B, Khan M, Darlison M Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson, 2008.PMID 18817553
[9]Vichinsky EP Clinical manifestations of α-thalassemia. Cold Spring Harb Perspect Med, 2013.PMID 23543077
[10]Lal A, Viprakasit V, Vichinsky E Disease burden, management strategies, and unmet needs in alpha-thalassemia due to hemoglobin H disease. Am J Hematol, 2024.PMID 39037279
[11]Hoffbrand AV, Taher A, Cappellini MD How I treat transfusional iron overload. Blood, 2012.PMID 22919029
[12]Piel FB, de Montalembert M, Das R Thalassaemia. Nat Rev Dis Primers, 2026.PMID 42426018