HEREDITARY

DISORDER OF
HAEMOGLOBI
NOPATHY
Ustas:Tamer Imad
Haematology department
•Aetiological classification :
1- Intrinsic abnormality:
a) Congenital:
i. Membrane defects.
ii. Haemoglobin defects.
iii. Enzyme defects.
 Haemoglobin abnormalities

These result from the following :

Synthesis of abnormal haemoglobin.
Reduced rate of synthesis of normal globin.
THALASSEMI
AS
 The Thalassemias
Syndromes in which the rate of synthesis
of a globin chain is reduced.
Thalasaemias are group of microcytic
hypochromic anaemias .
They classified into two main group:
I. Alpha (α2) thalassemia syndromes.
II. beta (β2) thalassemia syndromes.
 They are divided clinically into:
I. Thalassaemia major.
II. Thalassaemia intermediate.
III. Thalassaemia minor.
 The alpha thalassemia
These are usually due to gene deletions result in
a reduce rate or defective synthesis of alpha globin
chain.
Reduction in alpha chain synthesis affect in the
normal haemoglobin production which form Barts

haemoglobin (γ 4) in fetus or Hb H (β4) in adult.

Classification and pathogenesis:-

The synthesis of alpha chains in the

haemoglobin molecule is directed by two
duplicated gene( 4 gene) on the pair of
chromosomes 16.
Two main types of alpha thalassaemia are
regnized on the basis of the extent of reduction in
Alpha chains synthesis:
α0 : characterized by complete absence of α
chain.
α+: characterized by complete suppression of α
chain.
Alpha Thalassaemia minor:-

α+ trait(Heterozygous - α / α α)
Deletion of one gene from one α chains.

Homozygous α+ (- α/ - α)
Deletion of one gene from both α chains.

α0 trait(Heterozygous - / α α) :
Deletion of two genes from one α chains.
 Clinical feature:-
Alpha Thalassaemia minor:-
Mild to moderate anaemia.
Hb level is usually normal or mildly reduced.
PCV is usually normal or mildly reduced.
Plateteles count is normal.
Blood indices: MCV :Low. MCH :Low .
Blood picture:
RBCS: Microcytic hypochromic red cell.
WBCs : Looked as normal.
PLTS: Normal morphology and distribution.
Alpha Thalassaemia intermediate:-

Deletion of three genes from α chains( double

heterozygous for α+(--/-α) and α0 (- -/- α).
Haemoglobin H disease in adult.
 Clinical feature
Alpha Thalassaemia intermediate:-

Moderate anaemia.
Mild jaundice.
Spleenomegaly.
Hb level : reduced.
PCV :reduced.
RBCs: elevated.
Plateteles count is normal.
Blood indices: MCV :Low(less than 60 fl). MCH :Low .
Blood picture:
RBCS: Microcytic hypochromic red cell.Target
cell,basophilic stippling
WBCs : Looked as normal.
PLTS: Normal morphology and distribution.
Mild reticulocytosis.
Hb H inclusions appear like the surface of the golf ball
when stained by supravital stain.
Alpha Thalassaemia major:-

Deletion of four genes from α chains.

Homozygous α0 genes (--/--).
Haemoglobin barts in fetus lead to hydrops fetalis.
 Clinical feature
Alpha Thalassaemia major:-

Hydrops fetalis:
is the most severe manifestation of the
alpha thalassaemia gene resulting
intrauterine death.
 The beta thalassemia

These syndromes is due to gene mutation result

in a reduce rate or defective synthesis of beta
globin chain.
Reduction in the amount of normal Hb A results
in microcytic hypochromic anaemia.
Classification and pathogenesis:-

Two main types of beta (β- thalassaemia are

regnized on the basis of the extent of reduction in
beta chains synthesis:
β0 : characterized by complete absence of beta
chain.
β+: characterized by complete suppression of beta
chain.
 Β thalassaemia major
Also known as Mediterranean or Cooley's
anaemia.
It is homozygous state for either β+ (- β/- β) or β0
(--/--) genes.
In the absence of β chain synthesis ,excess α –
chains precipitate in erythroblast and in mature red
cells causing severe ineffective erythropoeisis and
haemolysis.
 Clinical feature
Severe anaemia becomes apparent at 3-6 months
after birth.
Enlargement of the liver and spleen .
Expansion of bone due to intense marrow
hyperplasia lead to thalassaemic face and thining of
the cortex of many bones with tender to fractures
and bosing of the skill with hair-on end appearance
on X-ray. .
 Laboratory diagnosis
Severe hypochromic microcytic anaemia with
raised reticulocytes count and white cells count.
Blood picture shows microcytic hypochromic cells,
target cell nucleated RBCs, Polychromsia and
basophilic stippling.
The osmotic fragility test reveals an increase.
Hb electrophoresis reveals absence of Hb A with
increase level of Hb A2.
 Β thalassaemia minor
This disorder in the heterozygous state for the beta
thalassaemia gene.
Usually symptoms are less abnormal.

Laboratory diagnosis:-

•Characterized by microcytic hypochromic blood picture .

•The red cells market high.
•Hb level :10 -15g/dl.
•Hb A2: increases above 3.5%.
•Hb F: increased.
 Β thalassaemia intermedia

Case of thalasaemia of moderate severity and

the severity lies between minor and major forms.
Clinical feature:-
•Moderate anaemia.
•Enlarged liver and spleen.
•Bone deformality.
Laboratory diagnosis:-

Moderate anaemia with microcytic hypochromic

picture.
Hb electophoresis.