THALASSEMIA

B A D H A I , B I J AY
CHALISE, SAGAR
CARIÑO, ZERWIN DEAN
CUISON, MIRZI DOROTHY
 HEMOGLOBIN
• Quaternary structure consists of 141 amino
acids in the alpha chain and 146 amino acids
in the beta chain.
• The two identical α chains and the two
identical β chains are arranged tetrahedrally.
• Heme is a prosthetic group.
• Fe(II) ion is at the center of the heme for
oxygen binding. Each subunit of hemoglobin
has a histidine residue that forms a covalent
bond to the heme.
• The two identical alpha chains and two
identical beta chains are arranged
tetrahedrally. These units are held together
by hydrophobic interactions, hydrogen
bonding, and salt bridges.
 THALASSEMIA
• Came from the Greek word “Thalassa” which means “sea” and “Hema“
which means “blood”.
• Thalassemia is an inherited blood disorder that causes patients body to
have less hemoglobin than normal thus, can cause anemia, leaving
patients fatigued.
• If patients have mild thalassemia, they might not need treatment
however, more severe forms might require regular blood transfusions.
THALASSEMIA
X-linked alpha thalassemia.
 EPIDEMIOLOGY
 Alpha-Thalassemia- prevalent in Asian and African population.
 Beta-Thalassemia- prevalent in Mediterranean population. (Example:
Greece and Turkey)
 There is no effective screening method in place.
PATHOPHYSIOLOGY and ETIOLOGY
 Hemoglobin
-Protein molecule in the red blood cells that carries oxygen.
 In Thalassemia there is an excessive destruction of red blood cells, which results
in Anemia.
 Common cause of Microcytic Anemia.
 Caused by deletions or mutations of Hb genes, results in underproduction or
absence of alpha or beta chains
 It is an Autosomal Recessive Disease
PATHOPHYSIOLOGY and
ETIOLOGY
PATHOPHYSIOLOGY and ETIOLOGY
 Thalassemia Minor
Only one parent is a carrier.
Develops minor symptoms.
 Thalassemia Major
Both parents are carriers.
Develops major symptoms.
 PATHOPHYSIOLOGY and ETIOLOGY
 Alpha globin protein chains consist of four genes, two from each parent.
 Beta globin protein chains consist of two genes, one from each parent.
 Decreased synthesis of Alpha or Beta chains of Hemoglobin.
 Results in Red Blood Cell Deformity that will result in decrease level of oxygen.
 In Alpha Thalassemia it depends on the number of gene mutations that is inherited
from the parents.
 In Beta Thalassemia it depends on which part of the hemoglobin molecule is
affected.
 There are 200 identified mutations as the culprit of thalassemia
 ALPHA THALASSEMIA
 ABNORMALITY: Hemoglobin does not produce enough alpha protein
 characterized by a reduced production of the α-globin chains of the hemoglobin
molecule, while the β-globin chains are normally produced. This means that there
will be an accumulation of the β-(unpaired) globin chains, within the developing red
cell.

 Four genes are involved in making the alpha hemoglobin chain. 2 from each parent
• One mutated gene: No Signs and Symptoms. But is a carrier of the disease
• 2 mutated genes: Mild symptoms. Might be called alpha-thalassemia trait.
• 3 mutated genes : Signs and symptoms are Moderate to Severe
TYPES OF ALPHA THALASSEMIA

1. Alpha plus (α+) thalassemia

carrier
2. Alpha zero (α0) thalassemia
carrier
3. Hgb H disease
4. Alpha Thalassemia Major
Silent Carrier State/ Alpha plus (α+) thalassemia
carrier
• Difficult to detect
• It causes no health problems
• Lack of alpha protein is so small that the
hemoglobin functions normally
• Diagnosis is through deduction – a normal
individual has a child with alpha
thalassemia trait or hemoglobin H disease.
• individual has only one (out of four) non-
functional gene. The other three α-globin
genes produce nearly normal amounts of
hemoglobin.
Alpha Thalassemia Minor / Mild Alpha Thalassemia /
Alpha zero (α0) thalassemia carrier
• Lack of alpha protein is somewhat greater
• has two (out of four) α-genes missing
(deleted) or non-functional and is said to be a
carrier of alpha zero thalassemia.
• The two missing or defective genes, may be
on the same chromosome (cis position) or on
different chromosomes (trans position).
• Patients have smaller red blood cells and has
a mild microcytic anemia
• Many patients do not experience symptoms
• Often mistaken for iron deficiency anemia –
iron supplements has no effect
 Hemoglobin H Disease
• three α-globin genes are missing or non-functional
• Lack of alpha protein is great enough to cause severe anemia
and serious health problems
• Enlarged spleen
• Bone deformities
• Fatigue

• Named after the abnormal hemoglobin H ( created by the

remaining beta globin) that destroys red blood cells
• the excess β-chains which continue to be produced by the fully
functional β-globin genes, cannot pair up with the α-globin
chains to produce common hemoglobin (HbA).
• HbH has the capacity, like common adult hemoglobin (HbA) to
deliver oxygen efficiently to the tissues. It is, however, a
relatively unstable molecule, and its continuous breakdown
results in early death, or breakdown, of red cells (hemolysis).
FETAL HEMOGLOBIN VS ADULT HEMOGLOBIN
Alpha Thalassemia Major / Hemoglobin Bart’s Hydrops
Fetalis
• Four α-globin genes are deleted.
• Only Hgb Bart’s are formed - The gamma globins produced by the
fetus, join together to form an abnormal hemoglobin called
hemoglobin Barts
• This type of hemoglobin does not have any oxygen carrying capacity and
thus cannot sustain life.
• The term hydrops refers to the consequences of anemia, which
causes massive enlargement of liver and spleen and, eventually,
heart failure.
• In Utero, results to:
• profound anemia
• congestive heart failure (CHF)
• and death if not identified early enough for intrauterine transfusion to occur.
• The most severe form of alpha thalassemia
• Can only be treated by intra-uterine blood transfusions and regular
transfusions, after the baby is born.
• There is also an increased risk of maternal complications when the
fetus has hydrops.
 Beta Thalassemia
 Genetic disorder where
there's a deficiency in the
production of the β-
globin chains of
hemoglobin, which is the
oxygen carrying protein
in red blood cells
 Most common: In
Mediterranean, African
and South East Asian
populations.
 Types of Beta Thalassemia
 Thalassemia Major
• Cooley's Anemia
• Severe form of beta thalassemia
• Presence two abnormal genes that causes a severe decrease of Beta globin
production.
 Thalassemia Minor
• Presence of one normal gene and one with a mutation (carrier state)
• Mostly asymptomatic
• Very mild anemia.
  Thalassemia Intermedia
• • Presence of gene where there is diminished but not absent quantity of beta
globulin
• • Variable severity
 Molecular Genetics
 Mutation occurs in the beta globin
gene present on chromosome 11
 Occurs if reduced, or complete
absent beta globin chain synthesis.
 Autosomal recessive disease, two
mutated copies of the gene, one
from each parent, are needed to
develop the disease (β 0, β+).
 Beta thalassemia minor = 1 mutated gene (reduced or absent
production of beta globin chains)
 Beta thalassemia intermedia = 2 mutated genes that code for
reduced beta globin chain synthesis
 Beta thalassemia major = 2 β 0 mutations then no beta globin chains
are produced.
 Biochemical mechanism
 Free a-
chains
 Missing or
deficient B
globin
chains
 E BETA THALASSEMIA
 Abnormality: Hemoglobin E
 Common in Southeast Asian ancestry – Cambodians, Vietnamese, and
Thai
 Produced when Beta Thalassemia is combined with hemoglobin E
 It is a moderately severe anemia
 Symptoms are like Beta Thalassemia intermedia
SICKLE BETA THALASSEMIA
 Abnormality: Hemoglobin S (sickle cell disease)
 Common in Mediterranean ancestry – Italians, Greeks and Turks
 Produced when Beta Thalassemia is combined with hemoglobin S
 When no beta globin is produced by the beta gene, the condition is
almost identical with sickle cell disease.
 The more beta globin produced by the beta gene, the less severe the
condition.
 COMPLICATIONS
 Iron overload :-
• People with thalassemia can get
too much iron in their bodies,
either from the disease or from
frequent blood transfusions.
• Too much iron can result in
damage to your heart, liver and
endocrine system.
 May get frequent severe
infections, especially if
patients receive a lot of blood
transfusions.
 In cases of severe thalassemia
 Bone deformities. Thalassemia can make your bone marrow expand, thus resulting
in abnormal bone structure, especially in your face and skull. Bone marrow
expansion also makes bones thin and brittle, increasing the chance of broken bones.
 Enlarged spleen. This disease is often accompanied by the destruction of a large
number of red blood cells which causes spleen to enlarge and work harder than
normal
 Heart problems. Congestive heart failure and abnormal heart rhythms can be
associated with severe thalassemia.
 Slowed growth rates. Anemia can both slow a child's growth and delay puberty.
 DIAGNOSIS
 Before diagnosing a patient , doctor will interrogate with
following topics :
• Their family background

• Their ethnic group

• Will consider , whether their anemia is due to iron deficiency instead of

thalassemia
 So to diagnose this disease physician can
use some test
• Complete blood count test (CBC): here they
will look whether the no. of RBC is low, smaller
cells of RBC and low level of hemoglobin
• Hemoglobin test : here doctor will look for
mutated alpha or beta globin chains
 A reticulocyte count (a measure of
young red blood cells) may indicate that
your bone marrow isn’t producing
enough red blood cells.
 Genetic testing is used to diagnose alpha
thalassemia.
 Hemoglobin electrophoresis is used to
diagnose beta thalassemia.
 PREVENTION
 Can thalassemia be prevented?
• No, you can't but we can know whether anyone in the couple is carry the
gene by genetic testing. So, by knowing this one can get help during
pregnancy if they plan to conceive.
 Can thalassemia be cured?
• A bone marrow transplant from a compatible sibling offers the best chance at
a cure for thalassemia. Unfortunately, most people with thalassemia lack a
suitable sibling donor. Also, a bone marrow transplant is a high-risk procedure
that may result in severe complications, including death.
 TREATMENT
 A blood transfusion 
• It involves receiving injections of red blood cells through a vein to restore
normal levels of healthy red blood cells and hemoglobin. 
• Transfusion is received every 4 months for moderate or severe case.
• with beta thalassemia major, every two to four weeks. 

 Iron chelation 
• It involves the removal of excess iron from patient's body.
 Folic acid supplements 
• This can help patients body make healthy blood cells.
 TREATMENT
 Bone marrow and stem cell transplant
• It is received from a compatible related donor is the only treatment to cure
thalassemia. Compatibility means the donor has the same types of proteins,
called human leukocyte antigens (HLA), on the surface of their cells as the
person receiving the transplant. 
 Luspatercept 
• It is an injection that’s given every three weeks which can help patient body
make more red blood cells.

Heart disease from iron overload is the leading cause of death in people with
thalassemia, so keeping up with iron chelation therapy is extremely important.
 References
 Bajwa H, Basit H. Thalassemia. [Updated 2022 Jun 7]. In: StatPearls [Internet]. Treasure Island
(FL): StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK545151/
 https://www.mayoclinic.org/diseases-conditions/thalassemia/symptoms-causes/syc-20354995
 https://medlineplus.gov/ency/article/000587.htm
 https://my.clevelandclinic.org/health/diseases/14508-thalassemias?
fbclid=IwAR0rkwm0iuDdN_c3Lyr2Au9zK-9k1KTNslP2Dus7x1F-uQ6sLB2OCFQa-QU
 https://www.thalassemia.org/learn-about-thalassemia/about-thalassemia/
 https://thalassemia.com/alpha-thalassemia.aspx#gsc.tab=0
 https://thalassaemia.org.cy/education/learn-about-thalassaemia/haemoglobin-disorders/
alpha-thalassaemia/
Thank you for your attention