1. SECTIONS:
2. preface & acknowledgements
3. genetics at a glance
4. contacts, support & testing
5. testing & pregnancy
6. newborn screening
7. cancer in the family
8. cardiovascular conditions
9. chromosomal conditions
10. clotting & bleeding conditions
11. cystic fibrosis
12. diabetes
13. fragile X syndrome and other causes of developmental delay
14. haemoglobinopathies
15. hereditary haemochromatosis
16. neurofibromatosis
17. neurological conditions
18. psychiatric conditions
19. genetics in practice
20. emerging genetic technologies
21. glossary

Condition-specific information

 

β-Thalassaemia

 

Clinical features

1. The common clinical features of β-thalassaemia major manifest after birth, usually within 6 to 12 months and include:
2. Pallor
   
3. Lethargy
   
4. Poor appetite
   
5. Developmental delay
   
6. Failure to thrive
   
7. Irritability, difficulty settling
   
8. Splenomegaly, growth failure with bone changes, fractures and leg ulcers also develop during childhood
   
9. Haemolytic anaemia
10. Carriers for β-thalassaemia are usually asymptomatic but may have mild hypochromic anaemia.

 

Genetics

1. Haemoglobin A (HbA) contains two α-globin chains and two β-globin chains (α2β2).
   
2. HbA2 is a normal variant of haemoglobin and is composed of two α-globin and two δ-globin chains (α2δ2). It usually represents 2 to 3.5% of normal total adult haemoglobin.
   
3. HbF refers to fetal haemoglobin, a normal variant in fetal development that persists in small amounts postnatally. It is composed of two α-globin and two γ-globin chains (α2γ2) and usually represents less than 1% of normal total adult haemoglobin.
   
4. β-thalassaemia is caused by reduced or absent production of the β-globin chain of the haemoglobin molecule.
   
5. The β-globin gene (HBB) encodes the β-globin chain. Each individual has two copies of this gene, one from each parent.
   
6. β-thalassaemia major is caused by mutations in both copies of the β-globin gene, resulting in virtually no functional β-globin chains being produced. This is a severe medical condition requiring frequent blood transfusions and iron chelation therapy.
   
7. β-thalassaemia minor (also called β-thalassaemia trait) is the carrier state and is caused by a mutation in one copy of the β-globin gene. While this is not a serious medical condition, it manifests as reduced red cell indices and elevated concentrations of HbA2, and can be mistaken for iron deficiency.
   
8. β-thalassaemia major follows a pattern of autosomal recessive inheritance. Carriers have a 50% chance of passing the mutated β-globin gene to their children. Couples who are both carriers have a 25% chance of having an affected child. This risk applies for every pregnancy of that partnership.
   
9. Co-inheritance of β-thalassaemia minor and a haemoglobin variant (for example, Hb Lepore, HbC or HbE) may result in a form of β-thalassaemia major (see Other haemoglobinopathies caused by structural change). This is known as compound heterozygosity, as the two types of gene mutations are different.
   
10. Couples where one partner is a carrier for β-thalassaemia and the other is a carrier for α-thalassaemia are not at risk of having children with thalassaemia major.

 

Prevalence

1. There are particular sub-groups of the population who are at increased risk of being a carrier for
   α-thalassaemia:
2. 1 in 5 people of high-risk ethnic background (from the Middle East, Southern Europe, Indian subcontinent, Central and South East Asia and Africa) may carry a β-thalassaemia mutation
   
3. An individual with an MCH <27pg and/or MCV <80fL is at increased risk of having a thalassaemia minor carrier state. Some labs consider MCH ≤ 27pg and MCV ≤ 81fL
   
4. Individuals with a family history of β-thalassaemia major and/or β-thalassaemia minor
5. Also see Prevalence of haemoglobinopathies above.

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