This document discusses thalassemia, a blood disorder caused by mutations in hemoglobin genes. It provides information on the types of hemoglobin normally present at different stages of life, the genes responsible for alpha and beta chains, common mutations that cause thalassemia in India, and the decrease in globin protein synthesis that results in thalassemia. It also summarizes strategies for screening, diagnosis, and prevention of thalassemia births through counseling, prenatal testing, and preimplantation genetic diagnosis.

6. Haema
is Greek for blood.
Thalassa
is Greek for the sea.

8. 2ᶑ& 2 βchain
97% Adult haemoglobin
After birth Hb F is replaced by Hb A By six months of age
HbF: 2ᶑ& 2 ϒchain
At birth HbFis 70-90%, That fall to 25% by one month & <2% by one year of age
HbA2 : 2ᶑ& 2δchain
1.5 to <3.5% in normal adult
Types of Haemoglobin

9. The Gene of Alpha chain is
located on Chromosome 16.
Molecular aspect of Thalassaemia
The Gene of Beta chain is
located on Chromosome 11.

10. SEQUENCE OF BASES - “GENE”
Molecular aspect of Thalassaemia
T C G A T G
A G C T A C
Substitution, Deletion , Insertion of base pair of a gene results in another sequence of GENE called “ GENE MUTATION”.

11. Mutation causes either decrease or absent synthesis of globin protein .
•Decrease synthesis of Beta globin chain –
•Beta Thalassaemia
•Decrease synthesis of
•Alpha globin chain -
•Alpha Thalassaemia

12. •Approximately>200mutationsareknown
tocauseThalassemiaallovertheworld.
OfthemFivecommonThalassemia
mutationsin“INDIA”are–
•(IVS)1-S (G ->C)
•IVS 1 -1 (G->T)
•619 bp DELETION
•+1 Codon 8/9(+G)
•-Codon 41/42(-CTTT)
Beta -Thalassaemia Major

13. Beta -Thalassaemia Pathophysiology

17. Repeated BT causes iron load.
Desferoxamine is Given S.C. for 8 hours
every day for 5-6 days a week so as to chelate
iron load.

18. In 15 years of life span

24. Preventing the Birth of a “Thalassaemia” child is the only answer to this world wide problem

25. How does the birth of a thalassemia child occur ?

26. When both partners are carrier ,there is 25% chance of child to be affectectdwith Thalessaemiain each pregnancy
CARRIER
50 % CARRIER
25% NORMAL
25% T .MAJOR
CARRIER

27. But when only one partner is carrier then no child will be affected with Thaessemia
CARRIER
50 % CARRIER
NORMAL
50% NORMAL

28. -Carriers are Asymptomatic -They are silent culprit

31. Hb11.5 gm%
MCV60.6 MCH 18.6
MENTZER INDEX -MCV/TRBC 60.6/6.12 = 9.8

35. GeneticCounseling
If marriage is unavoidable due to cultural
& social reasons or diagnosed as carriers after
marriage or after conception

36. P
Then what is the option ?
PRENATAL DIAGNOSIS

37. G1P0A0
Dx
Haemogram
MCV 53.2
MCH 15.8
TRBC5.6
MCV/TRBC = 9.
Couple came for consultation at 18 weeks

38. G1P0A0
MCV 60.6
MCH 18.8
TRBC6.12
MCV/TRBC = 9.9
MCV 53.2
MCH 15.8
TRBC5.6
MCV/TRBC = 9.
Couple came for consultation at 18 weeks

39. G1P0A0
Thalassemia carrier
HbA2 4.6
HbA2 5.5
Couple came for consultation at 18 weeks
Thalassemia carrier

40. G1P0A0
Thalassemia carrier
Couple came for consultation at 18 weeks
Thalassemia carrier
Amniocentesis
Couple’s blood in EDTA along with amniotic fluid was
sent for Gene mutation analysis

41. Invasive
C.V.S.
Amniocentesis
Non Invasive
Free fetal DNA in maternal blood
PRENATAL DIAGNOSIS

42. Paternal mutant gene
Absent
Fetus is normal or
carrier
Continue the pregnancy
Paternal mutant gene
present
Fetus has 50%
chance being
Thalassaemia Major
Massively parallel DNA
Sequencing done
Maternal blood is collected for Isolation of Fetal DNA
fetal DNA is then tested for Paternal mutant gene
NONINVASIVE

43. PRENATAL DIAGNOSIS
INVASIVE PROCEDURE
under USG Guidance by 18 gauge needle
Trans abdominal Trans vaginal
-
Chorionic villous sampling (CVS)
11-14 weeks; Preferably at 11 weeks( 73 Days)

44. PRENATAL DIAGNOSIS
Trans abdominal -Ultrasound guided after 16 weeks
22 g needle
Initial -2-3 ml is discarded
Usually 20cc amniotic fluid
Results –2 to 3 weeks
AMNIOCENTESIS
INVASIVE PROCEDURE

45. Gene mutation in DNA obtained from FETUS is matched with family gene mutation
If fetus is normal
or carrier for thalassaemia
If fetus is thalassaemia Major
After genetic counseling couple should be given option for termination of pregnancy
Continue pregnancy
Gene mutation study Should be done among all carrier for Future family planning after birth

46. G3P1A2
Thalassemia carrier
Thalassemia carrier
Thalassemia Major

47. Pre-implantation Genetic diagnosis
PGDisastateoftheARTprocedureusedininconjunctionwithIVF.InwhichtheembryoistestedforGeneticdisorderspriortobeingplacedinthewombofthewoman-

48. Pre-implantation Genetic
diagnosis IVFBiopsy on Day 3Genetic AnalysisTransfer of Unaffected EmbryoNormal Baby-

49. Benefits of Pre-implantation Genetic diagnosis
Forcoupleswhohavealreadyanaffectedchild,PGDallowsHLAmatchingforpre- selectionofpotentialdonorprogenyfortheaffectedsiblingwhorequirebonemarrowtransplantation.
Psychologicalstressofterminationofpregnancycanbeavoided

51. World wide 240 million people are
carriers of β-thalassemia i.e.
1.5% of total world population.
Approximately 15 million people are estimated to suffer from
“Thalassemia Major”.
Every year One lac children are
born with thalassemia major

52. On an average 1 person in every 25 Indians is a thalassemia carrier i.e. approximately 30 million people are thalassaemia carrier .
Every hour “One” Thalassaemia major child is born i.e. every year approximately10,000 new Thalassaemia patients are born in India.

53. beta-thalassemia trait in India
Panjab 6.5%
Delhi 2.2 -9.2%
LarkanSindhi 17%
DaduSindhi 8%
Bhanishali15%
Lohana13.6%
Kerala 0.6%
Assam 5 %
Gujarat 10-15%

54. TO REDUCE TO PREVENT TO SET UP TO DIAGNOSE

56. Lack of
Education
Lack of
experts
Social factors
Lack of
National
policy
lack of
Fetal medicine
Centre
Lack Genetic entre
lack of
Funds
lack of
Screening

57. Lack of Education
Illiteracy is a big challenge for prevention of ThalassaemiaIn India

58. Lack of Education
lack of Pre marital screening
Detection of Carrier state
seems to be is a “stigma” to
their life and may
Affect their marriages
hence deprived of it.
Lack of Pre-conception counseling–
Even When family is having
affected Child, Couple have
unplanned pregnancy due
lack of knowledge & fund for
Screening methods.

59. Lack of Education
They do not have early
antenatal Booking
Hence deprived of
prenatal screening
And
prenatal diagnostic
care for
Thalassaemia

60. Lack of knowledge & attitude
Of pregnant woman & her family

61. Challenges of Social factors
Consanguineous Marriage
Marriage among Close blood relative is a big hurdle for prevention of Thalassaemia.
Feticide is “SIN”Hence they avoid termination of even when fetus is affected.

62. Lack of well equipped laboratory

63. Lack of genetic laboratory

64. Challenges of Economic burden
Fund for
Education, Training and awareness programmes
Fetal medicine Centre 50 -70 lacs
Lab -Cell counter 08-10 lacs
-HPLC 70-80 lacs
Genetic lab 25-75 lacs

65. Economic burden on patients

72. Mass screening :
Means screening of each individuals for thalassemia in reproductive age group (15 to 45 years)

76. P
Report should be high lighted with logo of ‘Thalassemia free India”.
Should calculate the Mentzer index and include it in haemogramreport
Should highlight the MCV, MCH, TRBC indices in haemogramreport

78. 3.Casscade screening :
Screening of relatives of index Thalassemia major

79. Government should formulate a policy for implementation of universal Thalassaemia screening programme“FREE OF COST” for infants, school and college going children, And those attending preconceptional and antenatal clinics. “Registration of marriage by the court should be done only when Blood report of Thalassemia screening is produced”

80. Like “Janani surksha yojana” the government should formulate the policy Of “ SWASTH SHISHU YOJANA” to prevent the birth of child with “THALASSEMIA” by providing prenatal diagnostic facility “FREE OF COST” at each and every corner of our country.
Psychological and financial support should be given to the pregnant women for safe termination of pregnancy if the fetus is affected with Thalassemia major.

83. Join hands

85. I AM A SMALL AND PRETTY CREATURE
WILL SOON COME TO THIS WORLD IN FUTURE.
BUT WOULD LIKE TO SEE SMILING DAD AND MOM
WHEN I COME OUT OF THE WOMB
THIS IS POSSIBLE ONLY WHEN
I BORN HEALTHY ONLY THEN
SO I APPEAL TO MY DOCTOR FRIENDS
DO INVESTIGATE ON ME BEOFRE JOURNEY ENDS
START WITH GENETIC COUNSELLING WITH MOM
BEFORE I ARRIVE IN THE WOMB
DO MOM’S HAEMOGRAM BLOOD TEST
TAKE MCV &MCH CRITERIA IN SET
IF MCV LESS THAN 75 & MCH LESS THAN 25 INDICE
THEN GO FOR ESTIMATION OF HbA2 IN PRECISE
IF VALUE COMES TO BE MORE THAN 3.5 PERCENT
LABLE MY MOM AS THALASSAEMIA CARRIER INSTANT
ADVISE FOR MY DAD’S CARRIER SCREEN TEST
IF COMES POSITIVE , GO FOR MY PRENATAL TEST
DO CVS AT 12 WEEKS OF MY GESTATIONAL LIFE
TAKE OUT VILLOUS TISSUE BY SMALL NEEDLE PIPE
SENT CVS TO GENETIC LAB FOR GENE MUTATION ANALYSIS
ALONG WITH REPORT OF MY PARENT’S BLOOD ANALYSIS
IF I STOOD THALASSAEMIA CARRIER OR NORMAL
CONTINUE MY JOURNEY IN THE WOMB AS USUAL
IF MY REPORT SHOW MUTATION FOR THALASSAEMIA DISORDER
TAKE ME OUT OF WOMB TO PREVENT THIS GENETIC DISOREDR
THIS WILL BE VERY PAINFUL TO MY MOM & DAD
FOR ME ALSO, NOT TO GET ENTERY IN THIS WORLD
HENCE I APPEAL TO YOU ALL MY DEAR
GO FOR PREMARITAL SCREENING WITHOUT FEAR
SO THAT MY LIFE NEVER COMES IN DANGER ZONE
AND I COMLPETE MY JOURNEY HAPPILY IN THE WOMB
I WOULD LIKE TO SEE ALL PARENTS WITH HAPPY & SMILLING FACE
AND MY NATION WILL SHINE AS THALASSAEMIA FREE IN WORLD RACE
.

88. “INVITATION”
13THBIENNIAL CONFERENCE OF
“ISPAT”
JODHPUR
SUN CITY OF INDIA
13THBIENNIAL CONFERENCE OF
JODHPUR
SUN CITY OF INDIA