This document provides information about beta thalassemia, including its classification, epidemiology, etiology, clinical features, diagnosis, complications, management, prognosis, and prevention. It begins by defining beta thalassemia as a genetic disorder of hemoglobin synthesis where there is reduced or absent production of beta globin chains. It then discusses the different types of beta thalassemia, the genetic basis and inheritance patterns, clinical presentation including anemia and organomegaly, diagnostic testing including blood counts and hemoglobin electrophoresis, complications related to iron overload, and long-term management through blood transfusions and chelation therapy. The document concludes with topics of prognosis, highlighting increased mortality risks, and prevention through carrier screening,

1. Beta Thalassemia
and
Prevention of Thalassemia
Classification, Epidemiology, Etiology
Clinical Features, Diagnosis, Complications,
Management, Prognosis, Prevention
Prof. Imran Iqbal
Fellowship in Pediatric Neurology (Australia)
Prof of Paediatrics (2003-2018)
Prof of Pediatrics Emeritus, CHICH
Prof of Pediatrics, CIMS
Multan, Pakistan

2. In the name of Our Creator
Allah,
the most Gracious,
the most Merciful

3. OBJECTIVES
• What is Beta Thalassemia ?
• What are the different types ?
• How to differentiate it from other childhood anemias ?
• What are its complications ?
• How to manage the Thalassemic child ?

4. What is Beta Thalassemia ?

5. Structure of Hemoglobin

6. Types of Hemoglobin
• Adult Hemoglobin (Hb A) – a 2 b 2
- 97 % in normal adults
• Adult Hemoglobin (Hb A2) – a 2 d 2
- < 3% in normal adults
- mild increase in Thalassemia carriers
• Fetal Hemoglobin (Hb F) – a 2 g 2
- 60 – 80 % at birth
- < 5 % at 6 months
- main hemoglobin in Thalassemia patients

7. Beta Thalassemia
• Genetic disorder of Hemoglobin synthesis
• Reduced or absent production of Beta globin chains
• Excess Alpha chains in RBCs damage the RBCs
• Decreased RBC survival
• Increased destruction of RBCs in bone marrow and
peripheral circulation
• Clinical anemia

8. Beta Thalassemia
Genetics

9. Human DNA in each Cell

10. Abnormal DNA
• 2 beta globin genes are on
Chromosome no 11
• Mutation in beta globin
gene results in Beta
Thalassemia
• One gene abnormal – Beta
Thalassemia carrier
• Both genes abnormal – Beta
Thalassemia disease

11. Beta Thalassemia – Genetic Transmission
• Thalassemia is autosomal
recessive
• Thalassemia patient gets
two abnormal genes – one
each from his parents
• Thalassemia carrier gets
one abnormal gene from
one of his parents

12. Both parents are
carriers
One parent is
carrier
Beta Thalassemia – from Parents to Children

13. Thalassemia Patient
Two abnormal genes – one from each parent

14. Thalassemia Carrier
One abnormal gene – from one of the parents

15. Autosomal Recessive Inheritance
• When both parents are
Thalassemia carriers, What
are the chances of the next
baby being affected ?
• Next child suffering from
Thallasemia
= 25 % chances

16. Beta Thalassemia – Genetic Types
• b-Thalassemia Minor
• (carrier)
• (1 abnormal gene)
• asymptomatic
• b-Thalassemia Major
• (patient )
• (2 abnormal genes )
• Severe disease

17. Beta Thalassemia
Epidemiology

18. b-Thalassemia in Pakistan
 b-thalassaemia major is a major public health problem in
Pakistan
• Carrier rate 5-8 %
• 7-11 million carriers in the country
• ~100,000 patients (Only 28000 are registered)
• 6000 thousands new patients/year
• Each Pt needs 26 units blood/year i.e.
• 2.5 Million Unit blood is needed/year to support these patients
» ( Ahmad S et al Br J Haematol 1996)

19. Beta Thalassemia
Clinical Features

20. Beta Thalassemia – Clinical Types
• 3 clinical types of Beta Thalassemia
• b-Thalassemia Major ( 2 abnormal genes ) - Severe disease
• b-Thalassemia Intermedia ( 2 abnormal genes) - moderate
disease (different mutations)
• b-Thalassemia Minor (carrier)
- (1 abnormal gene) - asymptomatic

21. Case Scenario
• A 18 months old child
presents to the OPD with
the complaints of poor
feeding and frequent crying
for the last 6 months.
• On examination, weight of
the child is 8 kg. He has
marked pallor on his
tongue and hands. His
abdomen is distended. Liver
and spleen are palpable by
8 cm each below the costal
margin.

22. Beta Thalassemia Major
• Most common Hemolytic anemia in Pakistan
• Severe hemolysis
• Anemia starts in first six months of life
• Spleen enlarged early
• Significant bony changes develop gradually

23. Beta Thalassemia Major – Clinical Features
• Anemia (mild to severe, may be masked by blood transfusion)
• Jaundice (unconjugated, in some cases)
• Hepato-Splenomegaly
• Bony deformities (due to Bone Marrow expansion in poorly
transfused children of Thalassemia major)
• Iron-overload results in dark skin complexion

24. Clinical Features of Thalassemia Major

25. Severe Facial Deformities in Beta Thalassemia Major

26. X-ray Skull in Thalassemia
(Bone marrow expansion)

27. Beta Thalassemia
Diagnosis

28. Beta Thalassemia – Lab Diagnosis
• Hb and RBC count low
• Anemia is microcytic hypochromic (MCV, MCH, MCHC are low)
• Reticulocyte Count increased > 2 %
• Peripheral blood film shows target cells and Normoblasts
• Bone Marrow exam (rarely needed) shows Erythroid
Hyperplasia

29. Peripheral film in Thalassemia Major
• Anisocytosis, poikilocytosis
• Microcytosis, Hypochromia
• Reticulocytes increased
• Target cells, Normoblasts

30. Hemoglobin in Beta Thalassemia
• Beta globin chains not produced
• Hb A (a 2 b 2) is reduced
• Beta Thalassemia patients - Hb F (a 2 g 2) is increased to 20 – 90 %
• Beta Thalassemia carriers - Hb A2 (a 2 d 2 )is increased to > 3.5 %

31. Beta Thalassemia – Lab diagnosis
• Hb A = 32.5 %
• Hb F = 64.4 %
• Hb A2 = 3.1 %

32. Detection of Thalassemia Minor (carriers)
• Carriers are asymptomatic or may have mild anemia
• Carriers detected by Hb electrophoresis which shows raised
Hb A2 to > 3.5 %
• Diagnosis of parents as Thalassemia Carriers helps to confirm
the diagnosis of Thalassemia in the child

33. Beta Thalassemia – Genetic Diagnosis
• Detection of Thalassemia gene mutations in peripheral blood
samples
• Usually blood of patient, mother and father is analyzed for
detection of common mutations
• DNA analysis performed at major labs in Pakistan

34. Beta Thalassemia
Common Thalassemia Mutations in Multan, Pakistan

35. Beta Thalassemia
Differential Diagnosis

36. Differential Diagnosis
Iron deficiency Anemia and Thalassemia
Iron deficiency Anemia
• Onset in late infancy
• Slow developing anemia
• No splenomegaly
• Serum Ferritin low
• Reticulocyte count < 2 %
• Hb electrophoresis shows Hb A
Thalassemia
• Onset in early infancy
• Rapidly developing anemia
• Splenomegaly
• Serum Ferritin raised
• Reticulocyte count > 2 %
• Hb electrophoresis shows raised
Hb F

37. Beta Thalassemia
Complications

38. Complications
• Massive Hepatosplenomegaly
• Bony abnormalities (deformities, osteoporosis)
• Iron overload (Fe 1 mg in each ml of packed RBCs)
• Skin - dark pigmentation
• Liver dysfunction (fibrosis)
• Endocrine abnormalities (Hypothyroidism,
Hypoparathroidism, diabetes, short stature, delayed puberty)
• Cardiac failure (due to cardiac hemosiderosis)

40. Complications of Iron Overload in Thalassemia

41. Beta Thalassemia
Management

42. Beta Thalassemia – Management
• Blood Transfusions
• Iron Chelation Therapy
• Hydroxyurea
• Splenectomy
• Bone Marrow Transplant

43. Beta Thalassemia – Blood Transfusions
• Needed for developing Anemia
• Packed cells transfused
• Usually monthly transfusions
• Requirement increases with age
• Allergic reactions are common
• Iron overload is major complication

44. Beta Thalassemia – Iron Chelation Therapy
• Started when serum ferritin > 1000 ng/ml
• Deferasirox (oral)
• Deferioxamine (subcutaneous infusions by infusion pump)
• Deferiprone (oral)

45. Beta Thalassemia – Hydroxyurea
• Anti-metabolite medication
• Inhibits DNA synthesis
• Increases Hb F production
• Hydroxyurea decreases blood transfusion requirement in 70 %
children with Thalassemia
• Some patients remain transfusion free with mild to moderate
anemia

46. Beta Thalassemia – Splenectomy
• Indications
• Massive splenomegaly
• Blood packed cells transfusion requirement more than 200
ml/kg/yr
• Splenectomy
Decreases blood transfusion requirement
• Predisposes to infections
• Does not cure the disease

47. Beta Thalassemia – Bone Marrow Transplant
• Curative treatment for Beta Thalassemia
• Facilities being developed in Pakistan
• Cost Rs 2 – 3 million
• Success rate 60-80 %
• High risk procedure
• Matched HLA sibling donor needed

48. Beta Thalassemia
Prognosis

49. Prognosis of Thalassemia in Pakistan
• High morbidity (sickness)
• Patients need significant medical support and resources
• Life span shortened due to multiple complications
• High mortality
0
20
40
60
80
100
120
2 4 6 8 10 12 14 16 18 20 22 24 25
1996
2006

50. Beta Thalassemia
Prevention

51. Beta Thalassemia carriers in Pakistan
 Punjabi 4.6 %
 Pathan 5.2 %
 Sindhi 4.3 %
 Baluchi 8.0 %
 Urdu speaking 5.3 %
 Overall 5.5 %

52. Prevention of Thalassemia
• Carrier Screening – detect Thalassemia carriers in population
by Extended Family Carrier Screening
• Genetic Counselling – guide parents to understand genetic
transmission of disease
• Prenatal Diagnosis – detect Thalassemia before birth by
chorion villus biopsy

53. Prevention of Thalassemia - Carrier Screening
Types
• Mass population screening – screen all population - (5%
carriers)
• Screening in Pregnancy – screen all pregnant women……if
they are positive, screen their husbands - (5% carriers)
• Extended Family Screening – screen all members of extended
family of Thalassemia patients - (30 % carriers)
• Family members are likely to have common genes

54. Prevention of Thalassemia
Extended family Carrier Screening
• Detect Thalassemia Carriers in families of Thalassemia
patients by carrier screening (blood tests)
• Carrier screening of married couples to know the risk of birth
of Thalassemia children in their family
• Carrier screening before marriage to know the risk of birth of
Thalassemia children after marriage
• Carrier screening before marriage to avoid marriage between
Thalassemia carriers

55. Prevention of Thalassemia
Extended family Carrier Screening
Fig: 9.8. Coefficient of inbreeding and thalassaemia screening in the members of Family No: 5. (NA=not available for testing).
(S. Ahmed et al, NEJM 2002)

56. • Identify the carriers
• Genetic Counselling
about risk of birth of
Thalassemic child
• Offer prenatal diagnosis to
the affected couples
Prevention of Thalassemia - Genetic Counseling

57. Prevention of Thalassemia - Genetic Counseling
• To understand and adapt to medical, familial and
psychological consequences of Genetic Disease
• Understanding the chance of passing a genetic condition on to
children.
• To help the family learn more about the Thalassemia and
how it can affect the family.
• Guiding through decision-making about genetic testing, family
planning, or medical planning.
• Finding supportive resources to help manage a genetic
condition.

58. Prevention of Thalassemia – Prenatal Diagnosis
• Both parents are Thalassemia carriers
• Chorion villus biopsy to get fetal DNA at 8-10 weeks of LMP /
Gestation
• Genetic / DNA analysis to detect presence of Thalassemia in
fetus

59. Identify Couple at Risk
Pregnancy
Fetal Sampling
Lab Diagnosis
Affected Fetus Normal Fetus
Termination of Pregnancy
Prevention of Thalassemia – Prenatal Diagnosis

60. Punjab Thalassemia Prevention Program, Multan
Prenatal Screening (2017)
• Total samples = 1284
• Thalassemia fetus diagnosed = 374

61. Medical Ethics
Abortion / Termination of Pregnancy
• Medical ethics for Muslims is related to Islamic jurisprudence
or Fiqh based on Consensus view of scholars

62. Islamic view of Abortion
Abortion
is allowed to be performed
Prior to 120 days
from the start of conception
if
Fetus is having a proven, serious, untreatable
congenital malformation
or
is likely to develop serious disease or handicap after
birth

63. Thalassemia Prevention Programs have reduced
Thallasemia Births in many populations

64. Prevention of Thalassemia
What should We do ?

65. Unmarried Persons
• Know your Thalassemia status by a simple Blood Test (CBC
and Hb electrophoresis) before marriage
• If you are a Thalassemia carrier, know the Thalassemia status
of your “Would be” before marriage
• If both “Would be” parents are Thalassemia carriers, Prenatal
testing in every pregnancy

66. Married couples
• If married, both Husband and Wife get tested for Thalassemia
• If both parents Thalassemia carriers, Prenatal testing
(diagnosis before birth) for every pregnancy

67. Prevention of Thalassemia – Health Education

68. Prevention of Thalassemia – Health Education

69. Take Home Message
• Thalassemia is common in our children
• Anemia and Splenomegaly are important signs on
physical examination
• Hemoglobin Electrophoresis with increased HbF in blood
is required for diagnosis
• We need to focus on Prevention of Thalassemia in our
country
• Every person should know his Thalassemia carrier status