Page 105 - Essential Haematology

Chapter 7 Genetic disorders of haemoglobin / 91

ated), the state of the chromosome packaging appear to have been selected because the carrier
and various enhancer sequences all play a part in state aff ords some protection against malaria.
determining whether a particular gene will be
transcribed.
Thalassaemias

These are a heterogeneous group of genetic disor-
Haemoglobin a bnormalities
ders that result from a reduced rate of synthesis of

These result from the following: α or β chains. β - Thalassaemia is more common in
the Mediterranean region while α - thalassaemia is
1 Synthesis of an abnormal haemoglobin.
more common in the Far East.
2 Reduced rate of synthesis of normal α - or β -
globin chains (the α - and β - thalassaemias).
Table 7.1 shows some of the first group of syn-

dromes that arise from synthesis of an α or β chain Table 7.1 The clinical syndromes produced
with an amino acid substitution. In many cases, by haemoglobin abnormalities.
however, the abnormality is completely silent. Th e
Syndrome Abnormality
clinically most important abnormality is sickle cell
anaemia. Haemoglobin (Hb) C, D and E are also Haemolysis Crystalline
common and, like Hb S, are substitutions in the β haemoglobins (Hb S,
chain. Unstable haemoglobins are rare and cause a C, D, E, etc.)
chronic haemolytic anaemia of varying severity with Unstable haemoglobin
intravascular haemolysis (see Table 6.2 ). Abnormal Thalassaemia α or β resulting from
haemoglobins may also cause (familial) polycythae- reduced globin chain
mia (see Chapter 15 ) or congenital methaemoglo- synthesis

binaemia (see Chapter 2 ).
Familial polycythaemia Altered oxygen affi nity

The genetic defects of haemoglobin are the most
common genetic disorders worldwide. Th ey occur Methaemoglobinaemia Failure of reduction
(Hb Ms)
in tropical and subtropical areas (Fig. 7.3 ) and most
Thalassaemia
Sickle cell anaemia
Hb C
Hb D
Hb E

Figure 7.3 The geographical distribution of the thalassaemias and the more common inherited structural

haemoglobin abnormalities.