THALASSEMIA CLASS 11 PROJECT WORK BIOLOGY

I. INTRODUCTION
Thalassemia, one of the most prevalent hereditary diseases globally,
recognized by the World Health Organization (WHO) as a major global
health concern included in its global disease burden assessments.
Thalassemia are a heterogeneous grouping of genetic disorders that
result from a decreased synthesis of alpha or beta chains of hemoglobin
(Hb). Hemoglobin serves as the oxygen-carrying component of the red
blood cells. It consists of two proteins, an alpha, and a beta. If the body
does not manufacture enough of one or the other of these two
proteins, the red blood cells do not form correctly and cannot carry
sufficient oxygen; this causes anemia that begins in early childhood and
lasts throughout life. Thalassemia is an inherited disease, meaning that
at least one of the parents must be a carrier for the disease. It is caused
by either a genetic mutation or a deletion of certain key gene
fragments.
If any of proteins are defective or missing, you’ll have thalassemia.
 Alpha globin protein chains consist of four genes, two from each
parent.
 Beta globin protein chains consist of two genes, one from each
parent.
The thalassemia you have depends on whether your alpha or beta
chain contains the genetic defect. The extent of the defect will
determine how severe the condition is.
Most previous estimates of thalassemia incidence and mortality are
derived from published research reviews, national registries, and data
collected by the now-defunct WHO Hemoglobin Disorders Working
Group.According to a 2008 report by the WHO, over 40,000 babies are
born with β-thalassemia annually, with approximately 25,500 of these
cases being transfusion-dependent β-thalassemia. For every thousand
carriers of the thalassemia gene, outcomes differ starkly between high-

and low-income countries. While most carriers in high-income
countries may experience chronic disease conditions, in low-income
countries, most children with the disease die before the age of five.
Hemoglobinopathies, including thalassemia, account for 3.4% of global
mortality in children under five and 6.4% in Africa.
Previous studies have found that thalassemia prevalence is highest in
the Mediterranean, the Middle East, and Southeast Asia. However,
migration has led to a shift in its global distribution. As a result, β-
thalassemia has become increasingly common in traditionally non-
endemic areas, including Western Europe and North
America. According to a 39-year follow-up study, the lifetime cost of
treating TDT is estimated at $5.4 million. The majority of this cost is
attributed to iron chelation therapy (68%, or $3.7 million) and blood
transfusions (30%, or $1.6 million). Implementing cost-saving measures
in iron chelation therapy could reduce the estimated lifetime cost by
about 33%, bringing it down to $4.2 million. Therefore, the lifetime cost
of TDT is projected to range from $5 million to $5.7 million.15
II. CAUSES AND TYPES
1. Alpha thalassemia is caused by alpha-globin gene deletion which
results in reduced or absent production of alpha-globin chains.
Four genes are involved in making the alpha hemoglobin chain,
You get two from each of your parents. The seriousness of alpha-
thalassemia depends on how many copies of the genes are
missing:

 If one copy of the gene is missing, you'll have no symptoms of
thalassemia. But you carry the disease and can pass it on to your
children.
 If two copies of the genes are missing, your thalassemia symptoms
likely will be mild. You might hear this condition called alpha-
thalassemia trait.
 If three copies of the genes are missing, your symptoms likely will be
moderate to severe.
It's rare to be missing all four copies of the genes. It usually leads to
stillbirth (the death of a baby before or during birth). Babies born with four
missing genes often die shortly after birth. Or they need blood
transfusions for the rest of their lives.
2. Beta thalassemia results from point mutations in the beta-globin
gene. Two genes are involved in making the beta hemoglobin
chain. You get one from each of your parents. Small changes in
the gene cause beta-thalassemia. These changes lead to reduced
production of the beta chain. If you inherit:
 One gene with changes, you'll usually have mild symptoms.
This condition is called nontransfusion-dependent
thalassemia. If you have no symptoms, you may hear your
condition called beta-thalassemia trait or thalassemia minor.
 Two genes with changes, your symptoms typically will be
moderate to severe. This condition is called transfusion-
dependent beta-thalassemia or thalassemia major.
Babies born with two changed beta hemoglobin genes usually are
healthy at birth. They often get symptoms within the first two years of
life. But it is possible to get a milder form of the disease with two
changed genes.

III. SYMPTOMS
Thalassemia presentation varies widely depending on the type and
severity. A complete history and physical examination can give several
clues that are sometimes not obvious to the patient themselves. The
following findings can be noted:
Skin
Skin can show pallor due to anemia and jaundice due to
hyperbilirubinemia (a condition characterized by elevated levels of bilirubin
in the blood, leading to jaundice). Patients usually report fatigue due to
anemia as the first presenting symptom.
Musculoskeletal
Extramedullary expansion of hematopoiesis (the formation of blood cells
outside the bone marrow) results in deformed facial and other skeletal
bones and an appearance known as chipmunk face.
Cardiac
Iron deposition in cardiac myocytes (units of muscle tissue) due to
chronic transfusions can disrupt the cardiac rhythm, and the result is
various arrhythmias (an irregular heartbeat). Due to chronic anemia,
heart failure can also result.
Abdominal
Chronic hyperbilirubinemia can lead to precipitation of bilirubin gall
stones and manifest as typical colicky pain of cholelithiasis.
Hepatosplenomegaly can result from chronic iron deposition and also
from extramedullary hematopoiesis in these organs. Splenic infarcts or
autophagy result from chronic hemolysis due to poorly regulated
hematopoiesis.
Slow Growth Rates Anemia can inhibit a child's growth rate, and
thalassemia can cause a delay in puberty. Particular attention should
focus on the child's growth and development according to age.

Iron overload. People with thalassemia can get too much iron in their
bodies. This can be due to the disease or to frequent blood
transfusions. Too much iron can result in damage to the heart, liver,
and glands that make and release hormones.
Infection. People with thalassemia have a higher risk of infections. This
is especially true if they've had their spleens removed.
Enlarged spleen. The spleen is an organ that helps the body fight
infection. It also helps remove old or damaged blood cells. Often,
thalassemia happens along with the destruction of a large number of
red blood cells. This causes the spleen to get bigger and work harder
than usual.
An enlarged spleen can make anemia worse. It also can reduce the life
of red blood cells received in a transfusion. If spleen grows too big, the
health care professional might recommend surgery to remove it.
IV. DIAGNOSIS
1. Complete blood count (CBC): CBC is often the first
investigation in a suspected case of thalassemia. A CBC
showing low hemoglobin and low MCV (a blood test that
measures the average size of your red blood cells) is the first
indication of thalassemia, after ruling out iron deficiency as
the cause of anemia. The calculation of the Mentzer
index (mean corpuscular volume divided by red cell count) is

useful. A Mentzer lower than 13 suggests that the patient
has thalassemia, and an index of more than 13 suggests that
the patient has anemia due to iron deficiency.
2. Iron studies (serum iron, ferritin, unsaturated iron-binding
capacity (UIBC), total iron-binding capacity (TIBC), and
percent saturation of transferrin are also done to rule out
iron deficiency anemia as the underlying cause.
3. DNA analysis: These tests serve to help confirm mutations in
the alpha and beta globin-producing genes. DNA testing is
not a routine procedure but can be used to help diagnose
thalassemia and to determine carrier status if needed.Since
having relatives carrying mutations for thalassemia increases
a person's risk of carrying the same mutant gene, family
studies may be necessary to assess carrier status and the
types of mutations present in other family members.
4. Hemoglobin electrophoresis Hemoglobin electrophoresis is
the process healthcare providers use to analyze hemoglobin
in your red blood cells. Hemoglobin electrophoresis helps
diagnose serious conditions like sickle cell anemia. It’s also
one of several tests that screen newborn babies for sickle
cell anemia and other rare but serious illnesses.
5. Multisystem evaluation: Evaluation of all related systems
should be done on a regular basis due to their frequent
involvement in the disease progression. Biliary tract and gall
bladder imaging, abdominal ultrasonography, cardiac MRI,
serum hormone measurements are a few examples that can
be done or repeated depending on the clinical suspicion and
case description.

Hemoglobin electrophoresis
Hemoglobin electrophoresis uses electrical charges to separate
hemoglobin types so healthcare providers can compare the level of
each type with normal levels. The major hemoglobin types have
different electrical charges. Here’s the typical test procedure:
 Healthcare providers place dissolved red blood cells from the
sample on a cellulose strip.
 Then, they put the strip with the sample into a machine called an
electrophoresis chamber. The chamber is a machine that passes
electrical currents through the sample.
 Hemoglobin types react to the electric current, moving away from
each other. Eventually the hemoglobin types appear as different-
colored bands.
 Healthcare providers compare the test results with results from a
normal hemoglobin sample.
 Hemoglobin type levels that are too high or too low may be signs
of a blood disorder. For example, if your hemoglobin Type S looks
different from a normal Type S, it could mean you have sickle cell
anemia.
V. Prevention
Beta thalassemia might be prevented by the identification of carrier,
‐
prenatal diagnosis, and genetic counseling (Origa & Comitini, 2019).
Genetic counseling offers the evidence for the risk of carriers of both
parents and risk in offspring. Prenatal diagnosis can be carried out by a

study of gene of fetus about 4–5 months of development or sampling at
11 weeks of gestation from chorionic villi. Examination of fetal DNA in
the serum of mother and investigation of fetal cells in maternal blood
might be useful to detect mutations in father (Mavrou et al., 2007).
Lymphocytes, trophoblasts, and nucleated erythrocytes (NRBCs) are the
three types of cells, which are utilized as sources of fetus DNA (Khan et
al., 2019). The burden of thalassemia can be reduced by the prevention
of the birth of homozygotes. Since the last two decades, numerous
Mediterranean and Western countries have succeeded to make a
substantial alteration in the population of homozygote. Some republics
such as Turkey, Lebanon, Iran, Canada, Egypt, Malaysia, Pakistan, and
China also have thalassemia control programs (Italia et al., 2019).
VI. TREATMENT
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. Thalassemia treatment depends on the
type and severity of the disease.
Mild thalassemia (Hb: 6 to 10g/dl):
Signs and symptoms are generally mild with thalassemia minor and
little if any, treatment is needed. Occasionally, patients may need a
blood transfusion, particularly after surgery, following childbirth, or to
help manage thalassemia complications.
Moderate to severe thalassemia (Hb less than 5 to 6g/dl):
 Frequent blood transfusions: More severe forms of thalassemia
often require regular blood transfusions, possibly every few
weeks. The goal is to maintain Hb at around 9 to 10 mg/dl to give
the patients a sense of wellbeing and also to keep a check on
erythropoiesis ( process by which red blood cells (erythrocytes)
are produced in the bone marrow ) and suppress extramedullary

hematopoiesis(formation of blood cells outside the bone marrow) . To
limit transfusion-related complications, washed, packed red blood
cells (RBCs) at approximately 8 to 15 mL cells per kilogram (kg) of
body weight over 1 to 2 hours are recommended.
 Chelation therapy: Due to chronic transfusions, iron starts to get
deposited in various organs of the body. Iron chelators
(deferasirox, deferoxamine, deferiprone) are given concomitantly
to remove extra iron from the body.
 Stem cell transplant: Stem cell transplant, (bone marrow
transplant), is a potential option in selected cases, such as
children born with severe thalassemia. It can eliminate the need
for lifelong blood transfusions. However, this procedure has its
own complications, and the clinician must weigh these against the
benefits. Risks include including graft vs. host disease, chronic
immunosuppressive therapy, graft failure, and transplantation-
related mortality.
 Gene therapy: It is the latest advancement in severe thalassemia
management. It involves harvesting the stem cells (HSCs) from the
patient and genetically modifying them with vectors expressing
the normal genes. These are then reinfused to the patients after
they have undergone the required conditioning to destroy the
existing HSCs. The genetically modified HSCs produce normal
hemoglobin chains, and normal erythropoiesis ensues.
 Genome editing techniques: Another recent approach is editing
genomic libraries, such as zinc-finger nucleases, transcription
activator-like effectors, and cluster regulated interspaced short
palindromic repeats (CRISPR) with Cas9 nuclease system. These
techniques target specific mutation sites and replace them with
the normal sequence. The limitation of this technique is to
produce a large number of corrected genes sufficient to cure the
disease.

 Splenectomy: Patients with thalassemia major often undergo
splenectomy to limit the number of required transfusions.
Splenectomy is the usual recommendation when the annual
transfusion requirement increases to or more than 200 to 220 mL
RBCs/kg/year with a hematocrit value of 70%. Splenectomy not
only limits the number of required transfusions but also controls
the spread of extramedullary hematopoiesis. Postsplenectomy
immunizations are necessary to prevent bacterial infections,
including Pneumococcus, Meningococcus, and Haemophilus
influenzae. Postsplenectomy sepsis is possible in children, so this
procedure is deferred until 6 to 7 years of age, and then penicillin
is given for prophylaxis until they reach a certain age.
 Cholecystectomy: Patients can develop cholelithiasis due to
increased Hb breakdown and bilirubin deposition in the
gallbladder. If it becomes symptomatic, patients should undergo
cholecystectomy at the same time when they are undergoing
splenectomy.
 Diet and exercise:
Reports exist that drinking tea aids in reducing iron absorption
from the intestinal tract. So, in thalassemia patients tea might be
a healthy drink to use routinely. Vitamin C helps in iron excretion
from the gut, especially when used with deferoxamine. But using
vitamin C in large quantities and without concomitant
deferoxamine use, there is a higher risk for fatal arrhythmias. So,
the recommendation is to use low quantities of vitamin C along
with iron chelators (deferoxamine)
Thalassemia minor is usually asymptomatic and has a good
prognosis. It normally does not increase morbidity or mortality.
Thalassemia major is a severe disease, and the long-term
prognosis depends on the treatment adherence to transfusion
and iron chelation therapies

VII.CASE STUDIES
A. Patient Profile
Name: Baby Naseeba
Age: 16 months (1 year and 4 months)
Gender: Female
Chief Complaints
• Pallor (pale skin and tiredness) – for 1 month
• Breathing difficulty – for 5 days
Medical History
• Baby was apparently healthy until 6 months of age.
• At 6 months, symptoms of severe anemia were noticed.
• Underwent hemoglobin electrophoresis, which confirmed
Thalassemia Major.
• First blood transfusion was given at 8 months of age.
Transfusion Details
• Pre-transfusion Hemoglobin (Hb): 3 g/dL
• Post-transfusion Hemoglobin (Hb): 11 g/dL
• Regular blood transfusions were started and continue to manage
anemia.
Clinical Findings
• Severe anemia
• Failure to thrive (poor growth and development)
• Secondary malnutrition
• Enlarged liver and spleen (suspected from general findings)
• Mild breathing difficulty due to low oxygen-carrying capacity

Diagnosis
• Based on clinical signs, family history, and hemoglobin
electrophoresis:
- Confirmed diagnosis: Beta Thalassemia Major
Treatment Plan
• Lifelong blood transfusions every 2–4 weeks to maintain Hb >10 g/dL
• Iron chelation therapy to prevent iron overload (due to repeated
transfusions)
• Nutritional support and supplements
• Regular monitoring of growth parameters and organ functions
Preventive Measures for Family & Society
• Genetic counseling for the family
• Carrier testing of parents (likely both are thalassemia carriers)
• Prenatal testing for future pregnancies
• Community awareness to prevent inherited thalassemia
Conclusion
This case highlights the lifelong challenges faced by a child with
thalassemia major, including the need for regular medical support,
transfusions, and emotional and financial care. With early diagnosis and
appropriate treatment, children with thalassemia can live longer and
healthier lives. Genetic counseling and public awareness are key tools
in preventing this inherited disorder.
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B. Patient Details
 Age: 19 years
 Gender: Male
 Diagnosis: Beta-Thalassemia Major (diagnosed at age 1)
Symptoms and Diagnosis
 At age 1, the patient showed poor feeding, irritability, slow
development, and low weight.
 Blood tests showed very low hemoglobin (4 g/dL).
 A special test called hemoglobin electrophoresis confirmed Beta-
Thalassemia Major.
 He started regular blood transfusions, and his spleen was
removed at age 7.
Family History
 In 2014, his parents and all three siblings were found to be
thalassemia carriers (thalassemia minor).
 They were healthy but received genetic counseling to understand
the risks.
Complications
 In 2020, he was diagnosed with Type 1 Diabetes after high blood
sugar and weakness.
 In 2023, tests showed:
o Iron overload
o Liver enlargement (hepatomegaly)
o Mild lung fluid (pleural effusion)
o Thyroid problems

o Weak bones (osteoporosis)
Treatment
 Blood transfusions every 3 weeks
 Iron chelation medicine (Deferasirox) to remove extra iron
 Insulin injections for diabetes
 Calcium, Vitamin D, and Folic acid supplements
Conclusion
This case shows that Beta-Thalassemia Major is a serious condition
that needs lifelong care. It can lead to other problems like diabetes and
bone weakness. Early diagnosis, regular treatment, and family
awareness are very important to improve the patient’s life.
VIII. CONCLUSION
Thalassemia has negative repercussions for many organs, and
without a cure, it has high morbidity. The disorder is best
managed by an interprofessional team that includes a
thalassemia care team, cardiologist, hepatologist,
endocrinologist, and psychologist. Also, family care, nursing
support, and social support are an integral part of the
management. A lead consultant should be in charge of the
patient care, and a nurse specialist, along with other specialists in
the respective fields, should be involved to cover all the aspects
of the disease. Patient education is crucial, and social worker
involvement, including a geneticist, is essential. In some parts of
the world, preventive strategies include prenatal screening,
restrictions on issuing marriage licenses to two people with the
same disease. The screening of children and pregnant women
who visit clinicians is an effective strategy to limit the disease

morbidity. The social worker should ensure that the
caregiver/patient has adequate support and financial resources
so that they can continue with treatment. Nurses should educate
patients on the importance of treatment compliance to avoid
serious complications, as well as monitoring treatment progress.
Pharmacists may soon play a greater role as there are new drug
products to assist in gene therapy on the horizon that can
eliminate the need for ongoing transfusions.

THALASSEMIA CLASS 11 PROJECT WORK BIOLOGY

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