Thalassemia Presentation m2

8/8/2019 Thalassemia Presentation m2

1/37

The Most Common Hereditary Disorder

Worldwide


2/37

Hb-A


3/37

ThalassemiaA Multi-organ disorder

Organs affected that need close clinical

assessment:- Spleen (immunity)

- Bones

- Liver

- Glands

- Heart

- Teeth


4/37

THALASSEMIA MAJOR ANDTHALASSEMIA INTERMEDIA

Thalassemia Major Requiring regular transfusions to manage clinical

complications (e.g., severe anemia, bone changes,cardiac, hepatic, endocrine)

Thalassemia Intermedia Requiring no or infrequent transfusions. Complications

appear later in life (thrombophilia, pulmonaryhypertension).

Genotype of patients


5/37

Objectives of transfusion inthalassaemia major

Correction of anaemia Child grows normally as a result

Suppression of erythropoiesis

Prevention of skeletal abnormalities due tomarrow expansion

Prevention of liver and splenic enlargement

Prevention of hypermetabolic state


6/37

WHOM TO TRANSFUSE

Hb < 7 g/dl on 2 occasions, > 2 weeks

apart

HB > 7 g/dl with:

facial changes

poor growth

fractures

extramedullary hematopoiesis

Thalassemia Major


7/37

WHOM TO TRANSFUSE

Consistently declining hemoglobin level

Acute exacerbations of anemia

Fatigue, weakness, poor quality of life, poorgrowth

The appearance of serious complications: leg

ulcers, thrombosis, ulmonar h ertension.

Thalassemia Intermedia


8/37

TRANSFUSION PROGRAMS INTHALASSEMIA MAJOR

Hypertransfusion (Hb > 9g/dl)

*improved growth

*less organomegaly

*fewer fractures

*less facial deformity

*less impairment ofnormal activity


9/37


10/37

ManagementTreatment Cure

1. Blood Transfusion 1. Bone Marrow2. Iron Chelation 2. BM Transplantation3. Splenectomy (Stem Cell transplantation)

2. Manipulation of HbF

4.Vital Organ Evaluation 4. Gene Therapy


11/37

Iron loading inthalassaemia

Sources:

Increased absorption from gut

Multiple blood transfusions

Rate of iron loading can be estimated from:

Volume of blood transfusedAmount of iron accumulated from the gut


12/37

Molecular Genetics

in Thalassemia


13/37

Globin Production


14/37


15/37


16/37


17/37

What is b-Thalassemia ? Autosomal Recessive Hereditary Blood

Disorder ( qalassa ). Classification (Minor, Intermedia, Major).

Anemia, Retarded Growth, and Vital Organs

Complications.


18/37

Mode of Inheritance


19/37


20/37

DiagnosisClinical Signs

Minima: Asymptomatic Minor: Majority Asymptomatic

Intermedia: Symptomatic, Moderate Anemia

Major: Severe Anemia, Craniofacial Features,Retarded Growth, Splenomegaly, Iron Overload.


21/37

Experimental Approach

Buffy Coat Preparation

DNA Extraction

PCR

ARMS Direct Sequencing

Whole Blood (3-5 ml)

A lifi ti R f t M t ti S t


22/37

Amplification Refractory Mutation System


23/37


24/37

* A Normal Sequence For IVS-I-110

* A Heterozygote Patient For IVS-I-110

* A Homozygote Patient For IVS-I-110


25/37


26/37

* A Normal Sequence For Codon 37

* A Heterozygote Patient For Codon 37

* A Homozygote Patient For Codon 37


27/37

- 30

Cd6

- 28

Cd5

Cd27

IVS-I-110

Cd37

IVS-I-6

Cd 8/9

IVS-I-5

IVS-I-1

Cd30 Cd39

IVS-II-848IVS-II-1

Cd 106/107

IVS-IIExon 1 IVS-I Exon 2Exon 3

IVS-II-745

Localization of the 17b-Thalassemia Mutationsin the b-Globin Gene


28/37

Premarital Testing

-Test for carriers at the time of marriage

- Minimize or prevent marriage of carriers to

control the birth of new patients


29/37

Prenatal Diagnosis


30/37


31/37


32/37


33/37


34/37


35/37

Pre-implantation Testing


36/37


37/37

Genes Create The Vital Plan For What We Are,

What We Will Be And What We Will Pass OnTo Our Children

Documents

Thalassemia Presentation m2