Thalassemia is an inherited blood disorder characterized by reduced hemoglobin production. It is caused by mutations in genes that encode the alpha or beta globin chains that make up hemoglobin. There are different types of thalassemia depending on which chain is affected, including alpha-thalassemia affecting alpha chains and beta-thalassemia affecting beta chains. Symptoms range from none to severe anemia. Diagnosis involves blood tests like complete blood count and hemoglobin electrophoresis. Treatment depends on severity but may include blood transfusions, iron chelation therapy, and bone marrow transplantation.

1. Thalassemia
Dr. Vijay Pathak
MD (Ayu. Pediatrics)

2. INTRODUCTION
1. Thalassemia are inherited blood disorders characterized by decreased
hemoglobin production. Symptoms depend on the type and can vary from
none to severe.
2. Thalassemia is caused by mutations in the DNA of cells that make
hemoglobin
3. The mutations associated with thalassemia are passed from parents to
children.

3. • Hemoglobin molecules are made of chains called alpha and beta
chains that can be affected by mutations.
• In thalassemia, the production of either the alpha or beta chains are
reduced, resulting in either alpha-thalassemia or beta-thalassemia.

4. Structure of Hemoglobin

5. Haemoglobin structural biology
❑Hemoglobins are composed of two pairs of globin chains, each of which contains one
alpha-like (α-like) chain and one beta-like (β-like) chain.
❑Embryonic Hbs are expressed as early as four to six weeks of embryogenesis and disappear
around the eighth week of gestation as they are replaced by fetal Hb. Embryonic Hbs
include:
i. Hb Gower-1, composed of two ζ globins (zeta globins) and two ε globins (epsilon
globins) (ζ2ε2)
ii. Hb Gower-2, composed of two alpha globins and two epsilon globins (α2ε2)
iii. Hb Portland, composed of two zeta globins and two gamma globins (ζ2γ2)

6. Adult Hb V/S Fetal Hb

7. Fetal Hb
Fetal Hb (Hb F) is produced from approximately eight weeks of gestation
through birth, It declines during the first few months of life. Hb F is composed
of two alpha globins and two gamma globins (α2γ2).

8. Adult Hb
• Adult Hb (Hb A) is the predominant Hb in children by six months of age and
onward; it constitutes 96-97% of total Hb in individuals without a
hemoglobinopathy. It is composed of two alpha globins and two beta globins
(α2β2).
• Hb A2 is a minor adult Hb that normally accounts for approximately 2.5-3.5%
of total Hb from six months of age onward. It is composed of two alpha
globins and two delta globins (α2δ2).

9. Pathophysiology
• The thalassemias are classified according to which chain of the hemoglobin
molecule is affected.
• In α-thalassemias, production of the α-globin chain is affected, while in β-
thalassemia, production of the β-globin chain is affected.

10. • The β-globin chains are encoded by a single gene on chromosome 11;
α-globin chains are encoded by two closely linked genes on
chromosome 16.
• Thus, in a normal person with two copies of each chromosome, two
loci encode the β chain, and four loci encode the α chain.

11. Inheritance

12. Alpha-thalassemias
• The α-thalassemias involve the genes HBA1 and HBA2. Two gene loci and so
four alleles exist.
• Two alleles are maternal and two alleles are paternal in origin.
• The severity of the α-thalassemias is correlated with the number of affected
α-globin, more alleles involved, the more severe will be the manifestations
of the disease.

13. Alpha-thalassemias
• Alpha-thalassemias result in decreased alpha-globin production; therefore,
fewer alpha-globin chains are produced, resulting in an excess of β chains in
adults and excess γ chains in newborns.
• The excess β chains form unstable tetramers (called hemoglobin H or HbH of
4 beta chains), which have abnormal oxygen dissociation curves.

15. No of missing alleles Types of alpha thalassemia Symptoms
1 Silent carrier No symptoms
2 Alpha thalassemia trait Minor anemia
3 Hemoglobin H disease Mild to moderate anemia; may lead normal life
4 Hydrops fetalis Death usually occurs in utero or at birth
Types of alpha thalassemia

16. Beta-thalassemia
➢Beta thalassemias are due to mutations in the HBB gene on
chromosome 11, also inherited in an autosomal, recessive fashion.
➢Mutated alleles are called β+ when partial function is conserved and
βo when no functioning protein is produced.
a) β thalassemia major : caused by a βo/βo genotype.
b) β thalassemia intermedia : caused by a β+/βo or β+/β+ genotype.
c) β thalassemia minor : caused by a β/βo or β/β+ genotype.

17. Beta-thalassemia Inheritance

18. Delta-thalassemia
As well as alpha and beta chains present in hemoglobin, about
3% of adult hemoglobin is made of alpha and delta chains. Just
as with beta thalassemia, mutations that affect the ability of this
gene to produce delta chains can occur.

19. Signs and symptoms
✓Iron overload: People with thalassemia can get an overload of iron in their
bodies, either from the disease itself or from frequent blood transfusions.
✓Infection: People with thalassemia have an increased risk of infection. This is
especially true if the spleen has been removed.
✓Bone deformities: Thalassemia can make the bone marrow expand, which
causes bones to widen. This can result in abnormal bone structure, especially
in the face and skull.

20. Signs and symptoms
✓Enlarged spleen: The spleen aids in fighting infection and filters unwanted
material, such as old or damaged blood cells.
✓Slowed growth rates: anemia can cause the growth of a child to slow down.
✓Heart problems: Diseases, such as congestive heart failure and abnormal
heart rhythms, may be associated with severe thalassemia.

21. Diagnosis of Thalassemia
Thalassemia can be diagnosed via a
• Complete blood count,
• Hemoglobin electrophoresis,
• High-performance liquid chromatography,
• DNA testing,
• Mentzer index.

22. Hemoglobin electrophoresis

23. Mentzer index
The index is calculated from the results of a complete blood count.
Mentzer index = MCV, in fL / RBC, in Millions per microliter
If Mentzer index is less than 13, thalassemia is said to be more likely.
If Mentzer index is more than 13, iron-deficiency anemia is said to be
more likely.

24. Management of thalassemia
1. Mild thalassemia: People with thalassemia traits do not require medical or follow-up
care after the initial diagnosis is made.
2. Anemia : People with severe thalassemia require medical treatment. A blood
transfusion regimen was the first measure effective in prolonging life.
3. Growth hormone therapy : There is some evidence that growth hormone replacement
therapy may help to increase the rate at which children with thalassemia grow taller.

25. Management of thalassemia
1. Iron overload : Multiple blood transfusions can result in iron overload. The
iron overload related to thalassemia may be treated by chelation therapy
with the medications deferoxamine, deferiprone, or deferasirox.
2. Bone marrow transplantation : It may offer the possibility of a cure in
young people who have an HLA-matched donor. Success rates have been in
the 80–90% range.

26. THANK YOU