Hemoglobinopathies

Genes coding for globin chains

What is hemoglobinopathy?

Whenever the biological function is altered due to

mutation in haemoglobin

All hemoglobinopathies arise due to a genetic

mutation
What are the types of
hemoglobinopathies?
 Quantitative hemoglobinopathies :
Lack or decreased synthesis of alpha or beta globin
chain
Eg: alpha and beta thalassemia

 Qualitative or structural hemoglobinopathies :

Altered sequence of amino acids in globin chain
Eg: sickle cell disease , HbM, HbC
Thalassemia

 Caused due to genetic mutation

 Lack or decreased synthesis of α or β globin chain
 There is compensatory increase in other globin
chain – δ , γ
 Characterised by hypochromic anaemia
 Commonly seen in Mediterranean area
What are the types of thalassemia ?

 Αlphathalassemia – lack / reduced synthesis of

alpha globin

 Betathalassemia – lack / reduced synthesis of

beta globin chain
Alpha thalassemia
 Alpha thalassemia results in genetic defect in one or more
copies of alpha globin gene located in chr 16

 This results in decreased or total absence of alpha globin

chains

 Structure is normal , but due to reduced quantity function

is abnormal
Types of alpha thalassemia
Based on the no. of genes affected :

1. Silent carrier – when one gene is affected

2. Alpha thalassemia minor / trait – two genes

3. Hemoglobin H disease – three genes

4. Alpha thalassemia major / Hydrops fetalis/ Hb barts – four

genes
Spectrum of disease
Type Gene deletion manifestation

Silent carrier One gene deletion Asymptomatic

Sufficient alpha chain

Alpha thal minor Two gene deletion Mild anaemia

Hemoglobin H disease Three gene deletion Moderate to severe hemolytic

anaemia

Hydrops fetalis All four copies Incompatible

Still birth
Beta thalassemia

 Beta thalassemia results in genetic defect in one

or two copies of alpha globin gene located in chr
11

 This results in decreased or total absence of beta

globin chains
Types Gene deletion Clinical manifestation

Beta thal minor / trait Single Asymptomatic

B/B+ or B/B0

Beta thal intermedia B+/B+ or B+/B0 Mild anaemia

Beta thal major B0/B0 Severe anaemia

Bo is complete absence
B+ is partial absence
Clinical features
 Globin chain forms aggregates inside the cell –
inclusion bodies
 RBC destruction – hemolytic anaemia
 Peripheral smear shows – microcytic hypochromic
picture
 Compensatory increase in HbF in B thal

Anaemia , hepatosplenomegaly,
expansion of Bone marrow , bone
abnormalities , growth defect ,
jaundice
Sickle cell anaemia

 Anaemia due to abnormal haemoglobin synthesis (Hb S)

 Mutation of the gene coding the B globin chain leading to

abnormal amino acid sequence
Mutation in sickle cell anaemia

Alteration in the 6 position of

the B globin chain
What happens because of altered amino
acid?
 Valine being nonpolar is present instead of glutamate
which is polar and charged
 Thus there is reduction in the negative charge
 When the haemoglobin is deoxygenated it produces a
sticky hydrophobic projection in the outer surface of the
haemoglobin
 Which another haemoglobin is attached
Inheritance

 Sickle cell disease – homozygous , severe manifestation

 Sickle cell trait – single gene defect, mild symptoms

Sticky end formation
Clinical manifestation of sickling

 Sickled RBC block the minor vessels Hypoxia

 Cause ischemia to organs – autospleenectomy
 Sickled RBC undergo hemolysis – hemolytic anaemia
 Bone pains, repeated infections , growth failure ,
ulcerations
 Sickle cell crisis
Diagnosis

 Hemoglobin electrophoresis

 Sickling test
Treatment

 Sickle cell crisis – conservative management

 Blood transfusion
 Hydroxy urea, sodium butyrate, asprin – increases HbF
synthesis
Other hemoglobinopathies
 Hb E – replacement of glutamic acid by lysine, seen in
south asia , mild anaemia

 Hb C – glutamic acid replaced by lysine , no clinical

features , incidental finding

 Hb D – punjab variant seen in India , property similar to

HbS but no sickling

 Hb lepore and antilepore

Reason out …

 Why patients with sickle cell anaemia are not

affected by malaria ?

 Why do patients with SCA and thal have high HbF?

Case history
A 12 year old boy was admitted with history of severe bone
pains and yellowish discoloration of skin and sclera. On
examination he had pallor , icterus and mild
hepatospleenomegaly and was underweight for his age . His
Hb was 7g/dl and Peripheral smear showed the following
picture

What is the diagnosis and how do you confirm it ?

Case history
 A 10 months old female baby was admitted in the pediatric ward with
chest infection and fever . The mother gives history of poor feeding ,
repeated infection and breathlessness. The mother also gives similar
history of her brother’s child On examination the baby was
underweight, had palor and hepatomegaly . Hb was 8 g/dl , PS
showed microcytic anaemia. Hb electrophoresis showed . How do you
confirm the diagnosis