Page 336 - Textbook of Pathology, 6th Edition

320 disorder of HbC may occur as benign homozygous HbC chain synthesis. Thalassaemias were first described in people
disease, or as asymptomatic heterozygous HbC trait, or as of Mediterranean countries (North Africa, Southern Europe)
double heterozygous combinations such as sickle-HbC from where it derives its name ‘Mediterranean anaemia.’ The
disease and HbC-β thalassaemia. Word ‘thalassa’ in Greek means ‘the sea’ since the condition
was found commonly in regions surrounding the
HbD Haemoglobinopathy Mediterranean sea. The condition also occurs in the Middle
HbD occurs in North-West India, Pakistan and Iran. About East, Indian subcontinent, South-East Asia and, in general
3% of Sikhs living in Punjab are affected with HbD in blacks (see Fig. 12.27).
haemoglobinopathy (called HbD Punjab, also known as Hb-
Los Angeles). HbD Punjab arises from the substitution of GENETICS AND CLASSIFICATION
glutamine for glutamic acid at β-121 globin chain position. Thalassaemias are genetically transmitted disorders.
Normally, an individual inherits two β-globin genes located
HbE Haemoglobinopathy one each on two chromosomes 11, and two α-globin genes
HbE is predominantly found in South-East Asia, India, one each on two chromosomes 16, from each parent i.e.
Burma and Sri Lanka. HbE arises from the substitution of normal adult haemoglobin (HbA) is α β *. Depending upon
2 2
lysine for glutamic acid at β-26 globin chain position. Like whether the genetic defect or deletion lies in transmission of
other abnormal haemoglobins, HbE haemoglobinopathy may α- or β-globin chain genes, thalassaemias are classified into
also occur as asymptomatic heterozygous HbE trait, α- and β- thalassaemias. Thus, patients with α-thalassaemia
compensated haemolytic homozygous HbE disease, or as have structurally normal α-globin chains but their production
SECTION II
double heterozygous states in combination with other is impaired. Similarly, in β-thalassaemia, β-globin chains are
haemoglobinopathies such as HbE-β thalassaemia and HbE- structurally normal but their production is decreased. Each
α thalassaemia. of the two main types of thalassaemias may occur as
heterozygous (called α- and β-thalassaemia minor or trait), or
Haemoglobin O-Arab Disease as homogygous state (termed α- and β-thalassaemia major).
Hb O-Arab disease was first identified in an Arab family The former is generally asymptomatic, while the latter is a
but has now been detected in American blacks too. The severe congenital haemolytic anaemia.
homozygous form of the disease appears as mild haemolytic A classification of various types of thalassaemias
anaemia with splenomegaly. alongwith the clinical syndromes produced and salient
laboratory findings are given in Table 12.12.
Unstable-Hb Haemoglobinopathy
The unstable haemoglobins are those haemoglobin variants PATHOPHYSIOLOGY OF ANAEMIA IN
which undergo denaturation and precipitation within the red THALASSAEMIA
cells as Heinz bodies. These give rise to what is known as A constant feature of all forms of thalassaemia is the presence
congenital non-spherocytic haemolytic anaemia or congenital of anaemia which occurs from following mechanisms:
Heinz body haemolytic anaemia. These disorders have either
autosomal dominant inheritance or develop from sponta- α-Thalassaemia: In α-thalassaemia major, the obvious cause
neous mutations. The unstable haemoglobins arise from of anaemia is the inability to synthesise adult haemoglobin,
either a single amino acid substitution in the globin chain or while in α-thalassaemia trait there is reduced production of
due to deletion of one or more amino acids within the β- normal adult haemoglobin.
globin chain so that the firm bonding of the haem group β-Thalassaemia: In β-thalassaemia major, the most impor-
within the molecule is disturbed leading to formation of tant cause of anaemia is premature red cell destruction
Haematology and Lymphoreticular Tissues
methaemoglobin and precipitation of globin chains as Heinz brought about by erythrocyte membrane damage caused by
bodies. the precipitated α-globin chains. Other contributory factors
Over 100 unstable haemoglobins have been described. are: shortened red cell lifespan, ineffective erythropoiesis,
They are named according to the place where they are and haemodilution due to increased plasma volume. A
encountered. For instance: Hb-Koln, Hb-Hammersmith, Hb- deficiency of β-globin chains in β-thalassaemia leads to large
Zurich, Hb-Sydney, and so on. The diagnosis of unstable Hb excess of α-chains within the developing red cells. Part of
disease is made by test for Heinz bodies and by haemoglobin these excessive α-chains are removed by pairing with γ-globin
electrophoresis. chains as HbF, while the remainder unaccompanied α-chains
precipitate rapidly within the red cell as Heinz bodies. The
REDUCED GLOBIN CHAIN SYNTHESIS: precipitated α-chains cause red cell membrane damage.
THALASSAEMIAS During their passage through the splenic sinusoids, these
red cells are further damaged and develop pitting due to
DEFINITION removal of the precipitated aggregates. Thus, such red cells
The thalassaemias are a diverse group of hereditary disorders
in which there is reduced synthesis of one or more of the *In a normal adult, distribution of haemoglobin is as under: HbA (α β )
2 2
globin polypeptide chains. Thus, thalassaemias, unlike = 95-98%, HbA2 (α 2 δ 2 ) (a minor variant of HbA) = 1.5-3.5%, HbF (α 2 γ 2 ) =
haemoglobinopathies which are qualitative disorders of less than 1%. But the level of HbF in children under 6 months is slightly
haemoglobin, are quantitative abnormalities of polypeptide globin higher.