Thalassaemia
Inherited disorders of haemoglobin production causing variable anaemia and iron overload.
Overview
Thalassaemia syndromes result from reduced alpha or beta globin chain synthesis. Severity ranges from silent carrier state through transfusion-independent (intermedia) to transfusion-dependent (major) disease. Lifelong transfusion + iron chelation are mainstays; gene therapy and BCL11A modulation are transformative for selected patients.
Symptoms
- • Severe anaemia from infancy in beta thalassaemia major
- • Failure to thrive, hepatosplenomegaly, skeletal deformity (frontal bossing)
- • Jaundice, gallstones
- • Iron overload features: cardiac, endocrine, hepatic dysfunction
- • Alpha thalassaemia: variable — from silent to hydrops fetalis
Risk factors
- • Mediterranean, Middle Eastern, South and South-East Asian, African ancestry
- • Consanguinity
- • Both parents being carriers
Causes
- • Beta thalassaemia: HBB gene mutations (autosomal recessive)
- • Alpha thalassaemia: HBA1/HBA2 gene deletions
- • Compound forms: HbE/β-thalassaemia common in South-East Asia
🚨 Red flags — seek urgent care
- • Hydrops fetalis (alpha thalassaemia major) — usually fatal in utero
- • Cardiac iron overload — heart failure, arrhythmia
- • Severe anaemia with growth failure in childhood
When to seek care
- • Antenatal screening positive — partner testing and counselling
- • Child with unexplained microcytic anaemia not responding to iron
- • Symptoms of iron overload in known patient
Diagnosis
- • FBC: hypochromic microcytic anaemia, raised RBC count
- • Hb HPLC/electrophoresis: HbA2 >3.5% suggests beta carrier; HbH inclusions in alpha
- • Genetic testing to confirm and quantify deletions/mutations
- • Iron studies and ferritin to distinguish from iron deficiency
- • Cardiac and liver T2* MRI to quantify iron load
Treatment
- • Transfusion-dependent thalassaemia: regular transfusion to maintain Hb >95–105 g/L
- • Iron chelation: deferasirox, deferiprone, desferrioxamine — start when ferritin >1000 µg/L
- • Folic acid; hydroxycarbamide selectively
- • Luspatercept reduces transfusion burden in beta thalassaemia
- • Allogeneic stem-cell transplant — curative in selected patients
- • Gene therapy (betibeglogene autotemcel, exa-cel) for transfusion-dependent disease
- • Splenectomy occasionally for hypersplenism (vaccination + prophylaxis essential)
Prevention
- • Antenatal screening and partner testing
- • Prenatal diagnosis if both parents carriers
- • Genetic counselling for at-risk communities
Complications
- • Cardiac iron overload — heart failure, arrhythmia (commonest cause of death)
- • Endocrine: diabetes, hypogonadism, hypothyroidism, hypoparathyroidism
- • Cirrhosis, osteoporosis, leg ulcers
- • Alloimmunisation, transfusion-transmitted infections (now rare)
Prognosis
With optimal transfusion and chelation, life expectancy approaches normal. Transplant and gene therapy can be curative for selected patients.
Education & self-care
Lifelong specialist care, adherence to chelation, and family screening are central. Modern therapies offer realistic hope of long, full lives — and increasingly, cure.
Frequently asked questions
Can I take iron tablets?
Not unless iron deficiency is proven — most thalassaemia patients are iron-overloaded.
Is thalassaemia trait a disease?
No — carriers are usually well but should know their status for family planning.
Is gene therapy available in the UK?
Yes — for selected transfusion-dependent patients in specialist centres.