Page 113 - Essential Haematology

Chapter 7 Genetic disorders of haemoglobin / 99

ineffective erythropoiesis. Conversely, patients with δ β - fusion chain is synthesized ineffi ciently and

β - thalassaemia trait who also have excess (five or six) normal δ - and β - chain production is abolished. Th e

α genes tend to be more anaemic than usual. Th e homozygotes show thalassaemia intermedia and the
patient with thalassaemia intermedia may show heterozygotes thalassaemia trait.
bone deformity, enlarged liver and spleen, extramed-

ullary erythropoiesis (Fig. 7.13 ) and features of iron Hereditary p ersistence of f etal
overload caused by increased iron absorption. Iron h aemoglobin
chelation with oral drugs or (gentle) venesections These are a heterogeneous group of genetic condi-

may be needed to treat this. Hb H disease tions caused by deletions or cross - overs aff ecting the
(three - gene deletion α - thalassaemia) is a type of production of β and γ chains or, in non - deletion

thalassaemia intermedia without iron overload or forms, by point mutations upstream from the γ -
extramedullary haemopoiesis.
globin genes or in the BCL11A gene (see p. 90) .

δ β - Thalassaemia

Association of β - t halassaemia t rait with

This involves failure of production of both β and δ o ther g enetic d isorders of h aemoglobin
chains. Fetal haemoglobin production is increased The combination of β - thalassaemia trait with Hb E

to 5 – 20% in the heterozygous state which resem- trait usually causes a transfusion - dependent thalas-
bles thalassaemia minor haematologically. In the saemia major syndrome, but some cases are interme-
homozygous state only Hb F is present and haema- diate. β - Thalassaemia trait with Hb S trait produces

tologically the picture is of thalassaemia intermedia. the clinical picture of sickle cell anaemia rather than
Haemoglobin F gives up oxygen to tissues less well of thalassaemia (see p. 104) . β - Th alassaemia trait
than haemoglobin A.
with Hb D trait causes a hypochromic microcytic
anaemia of varying severity.
Haemoglobin Lepore
This is an abnormal haemoglobin caused by unequal Sickle c ell a naemia

crossing - over of the β and δ genes to produce a
polypeptide chain consisting of the δ chain at its Sickle cell disease is a group of haemoglobin disor-
amino end and β chain at its carboxyl end. Th e ders resulting from the inheritance of the sickle β -

Figure 7.13 β - Thalassaemia

intermedia: magnetic resonance
imaging (MRI) scan showing
masses of extramedullary
haemopoietic tissue arising from
the ribs (arrowed) and in the
paravertebral region (arrowed)
without encroachment of the
spinal cord.