Page 107 - Essential Haematology

Chapter 7 Genetic disorders of haemoglobin / 93

Table 7.2 Classifi cation of thalassaemia.

Clinical
Hydrops fetalis Thalassaemia minor
0

Four gene deletion α - thalassaemia β - Thalassaemia trait
+

β - Thalassaemia trait

Thalassaemia major
Hereditary persistence of fetal haemoglobin
Transfusion dependent, homozygous

δ β - Thalassaemia trait

0

β - thalassaemia or other combinations

0

α - Thalassaemia trait

of β - thalassaemia trait

+
α - Thalassaemia trait

Thalassaemia intermedia
See Table 6.5
Genetic
Type Haplotype Heterozygous Homozygous
thalassaemia trait

(minor) *
†

α - Thalassaemias
0

α – – / MCV, MCH low Hydrops fetalis

0
+

α – α / MCV, MCH minimally As heterozygous α - thalassaemia

reduced
β - Thalassaemias

0
β MCV, MCH low Thalassaemia major (Hb F 98%,

(Hb A 2 > 3.5%) Hb A 2 2%)
+
β MCV, MCH low Thalassaemia major or intermedia

(Hb A 2 > 3.5%) (Hb F 70 – 80%, Hb A 10 – 20%,
Hb A 2 variable)

δ β - Thalassaemia and MCV, MCH low (Hb F Thalassaemia intermedia (Hb F
hereditary 5 – 20%, Hb A 2 100%)
persistence of fetal normal)
haemoglobin
Hb Lepore MCV, MCH low (Hb A Thalassaemia major or intermedia
80 – 90%, Hb Lepore (Hb F 80%, Hb Lepore 10 – 20%,
10%, Hb A 2 reduced) Hb A, Hb A 2 absent)
MCH, mean corpuscular haemoglobin; MCV, mean corpuscular volume.

* Occasionally heterozygous β - thalassaemia is dominant (associated with the clinical picture of thalassaemia intermedia).
There are several explanations.
† 0 +

Compound heterozygote α α ( – – / – α ) is haemoglobin H disease.

greater the α - chain excess, the more severe the tions. These mutations may be within the gene

‘
anaemia. Production of γ chains helps to mop up ’ complex itself or in promoter or enhancer regions.
excess α chains and to ameliorate the condition. Certain mutations are particularly frequent in some
Over 400 different genetic defects have now been communities (Fig. 7.7 ) and this may simplify ante-

detected (Figs 7.7 and 7.8 ). natal diagnosis aimed at detecting the mutations in

Unlike α - thalassaemia, the majority of genetic fetal DNA. Thalassaemia major is often a result

lesions are point mutations rather than gene dele- of inheritance of two different mutations, each