Haemolytic anaemias IV: genetic defects of haemoglobin – thalassaemia


c16-fig-5002



Normal haemoglobins


The haemoglobins are made up of four globin chains each containing a haem group. Embryonic haemoglobins (Portland, Gower I and II) are present in early fetal life. Fetal haemoglobin (Hb F, α2γ2¬) dominates by late fetal life. Hb F has a higher oxygen affinity than Hb A and this allows the fetus to obtain oxygen from the mother (Fig. 2.3). A switch occurs at 3–6 months in the neonatal period to normal adult haemoglobin (Hb A, α2δ2) (Fig. 16.1). Low levels of Hb F and the minor adult haemoglobin Hb A2 (α2δ2) are also present in normal adults (see Table 2.1).



Genetic disorders of haemoglobin



1 Disorders of α- or β-globin chain synthesis (the thalassaemias) (Table 16.1; Fig. 16.2);

2 Structural defects of haemoglobin which give rise to haemolysis (e.g. sickle cell anaemia, haemoglobin C);

3 Unstable haemoglobins (rare); and

4 Structural disorders giving rise to polycythaemia or methaemoglobinaemia (rare).


Table 16.1 Classification of thalassaemia




















Clinical phenotype Thalassaemia (thal) syndrome
Hydrops foetalis Homozygous α-thal major → complete lack of α-globin
Thalassaemia major Homozygous β or doubly heterozygous β thal → complete or almost complete lack of β-globin
Thalassaemia intermedia See below
Thalassaemia trait Heterozygous β-thalassaemia (β-thal minor, lack of one functional β-globin gene*)
Heterozygous α-thalassaemia (α-thal minor, lack of one or two α-globin genes†)

*Normal individual has two (one from each parent on each allele)


†Normal individual has four (two from each parent on each allele)


The first and second have a wide global prevalence, particularly where malaria is, or was, common, as the carrier states give some protection against falciparum malaria. Compound heterozygote states of a thalassaemic allele and a haemoglobin structural variant allele frequently occur and include sickle/β-thalassaemia and Hb E/β-thalassaemia.



Thalassaemia


These autosomal recessive syndromes divide into α- and β-thalassaemia depending on whether there is reduced synthesis of α- or β-globin (Table 16.1, Fig. 16.2).


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Jun 12, 2016 | Posted by in HEMATOLOGY | Comments Off on Haemolytic anaemias IV: genetic defects of haemoglobin – thalassaemia

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