Moleculer Basis Of Hemoglobinopathies

Question 1

What are Hemoglobinopathies

Answer 1

are a diverse group of inherited blood disorders that result from variations in the structure and/or synthesis of hemoglobin.

Question 2

Hemoglobinopathies mainly include

Answer 2

1- thalassemias

2- sickle cell diseases (SCD)

Question 3

If a Hemoglobinopathies disease is h eterogeneous

Answer 3

then multiple genes and alleles are causing it not only one ( Diverse]

Question 4

What is the diffrence btw adult hemoglobin (HbA) and Fetal hemoglobin (HbF)

Answer 4

Normal adult hemoglobin (HbA) is a tetramer of two α chains and two β chains (α2β2). Fetal hemoglobin (HbF) is a is a tetramer of two α chains and two γ chains (α2γ2).

Question 5

HbA2

What is it

Answer 5

is the third normal adult hemoglobin and it consists of 2 alpha and 2 delta subunits. This type constitutes only 2.5% of the
blood.

Question 6

We have the fetal blood in our blood its about

Answer 6

2.5%

Question 7

HBA in adult is about ….%

Answer 7

97

Question 8

The globin genes are located in ….chromosomes

Answer 8

2

ch16 and 11

Question 9

Why the alpha globin gene dosenot follow Mendalian inheritance

Answer 9

Bcs it has double the standered smount of genes —-> 4 genes

Question 10

What is the importance of The locus control region (LCR

Answer 10

is the one reponsible for the switch between the transcription of the gamma globin chain gene and the b-globin chain gene.
- switch from embryonic to fetal to adult

Question 11

LCR only found in … and …..

Answer 11

gamma globin chain gene and the b-globin chain gene

Question 12

What is the importance of PYR complex

Answer 12

controls the switch of expression from

• gamma. To
• beta

Question 13

Why alpha globin genes synthesis considered Constant

Answer 13

We have 2 copies of alpha and therefore 4 genes in our body. It is continuously expressed (Constant)

Question 14

What happened to gamma globin gene synthesis

Answer 14

gamma globin dramatically decreases at birth

Question 15

Notice how after birth, the synthesis of ….globin decreases and the …. globin production isincreased

Answer 15

• gamma

- beta

Question 16

gamma globinisreplacedalmost completely by beta at the age of ….. weeks

Answer 16

50

Question 17

Adult can have a traces of gamma

Answer 17

T

Question 18

Thalassemia is

Answer 18

Reduction in either alpha or beta globin chain level is low but the structure is normal

Question 19

Thalassemia can be classified as

Answer 19

1. α-thalassemia: patients have a defective expression of α-globin genes
2. β-thalassemia: patients have a defective expression of β-globin gene

Question 20

…….patesints requiring lifelong blood transfusions with complications in multiple organ systems.

Answer 20

Thalassemia

Question 21

(αα/αα) The deletion or inactivation of only one α-globin gene usually results in …..

Answer 21

insignificant hematologic findings

Question 22

What is the result in insignificant hematologic findings

Answer 22

silent carriers)

• normal phenotype
• genotypes (α-/αα) or (αα/α-)

Question 23

When 2 α-globin genes are deleted or inactivated, either on the same chromosome (αα/–) [southeast Asia] (cis) or on opposite
chromosomes (α-/α-) [African] (trans.), the affected person has

Answer 23

borderline anemia

Question 24

What is borderline anemia

Answer 24

On the line between anemic or not

Question 25

borderline anemia, characterized by....rbcs

Answer 25

microcytic | hypochromic

Question 26

HbH disease caused by

Answer 26

The deletion of three a-globin [only one functional α-globin gene]

Question 27

HbH disease: patients usually have anemia at ..... but ......

Answer 27

At birth | Not lethal

Question 28

intrauterine anemia happened bcz of

Answer 28

Hb Bart's hydrops fetalis syndrome

Question 29

There is a difference between HbH disease and HbH hemoglobin as well as Hb Bart's hemoglobin and Hb Bart's hydrops fetalis syndrome.

Answer 29

T

Question 30

Level of. Hb Bart’s, above 15% at birth is an indicative of HbH disease

Answer 30

T

Question 31

Hb Bart's (All gamma chains hemoglobin) can be present in HbH disease, but in small amounts that is not fatal like in Hb Bart's Hydrops Fetalis syndrome

Answer 31

T

Question 32

If you have 100% Hb barts then it will cause prenatal/postnatal death.

Answer 32

T

Question 33

excess β-globin chains form β4 homotetramers [HbH Hb] leads to

Answer 33

severe form of α-thalassemia.

Question 34

What is the diffrence btw HbH disease and HbH hemoglobin

Answer 34

* HbH Hb : homotetramer structure of 4 beta subunits | * HbH disease : Mutation in 3 genes when only one alpha is functional the other 3 are not working

Question 35

HbH disease are not transfusion-dependent but may require transfusion support for

Answer 35

infections and other oxidative stresses.

Question 36

The most common nondeletional form of HbH disease is

Answer 36

HbH Constant Spring

Question 37

what is β-thalassemia

Answer 37

The aggregation/deposit of alpha globins lead to ineffective erythropoesis leading to premature death of RBCs.

Question 38

Heinz bodies found in ....

Answer 38

hBH Erythrocyte

Question 39

β-Thalassemia

Answer 39

β-thalassemia is caused by the reduction (β+) or absence (β0) of β globin chains synthesis.

Question 40

There are three main types of β-thalassemia

Answer 40

1. β-thalassemia carrier state or minor (clinically asymptomatic; heterozygous) 2. β-thalassemia intermedia, (clinically and genotypically very heterogeneous) 3. β-thalassemia major (severe transfusion-dependent anaemia)

Question 41

The accurate identification of thalassemia intermedia versus thalassemia minor and major can be difficult if based on

Answer 41

clinical presentation alone

Question 42

is the most accurate approach for distinguishing between the different types of β-Thalassemia.

Answer 42

Genetic analysis

Question 43

Half of clinically severe thalassemia actually have the ....genotype

Answer 43

HbE/β- thalassemia genotype.

Question 44

There were two siblings with HbE/β-thalassemia and one of them died immediately after birth while the other survived. If u looked at the genetic composition what will u find ?

Answer 44

The one who died had a mutated α chain because we said it becomes more severe when its combined with alpha mutation!