Ch. 17 Hemoglobinopathies

Question 1

Destruction of Anemias can be either…

Answer 1

Hereditary
Acquired

Question 2

Hereditary Destruction Anemias can be classified as

Answer 2

Hemoglobinopathies
Membrane Structural defects
Enzyme defects in RBC defects

Question 3

Acquired Destruction Anemias can be classified as

Answer 3

Paroxysmal Hemoglobinuria
Immune mediated

Question 4

Hemoglobinopathies can be due to either

Answer 4

Defective globin synthesis (qualitative defect)
Underproduction of globin chains (quantitative defect)

Question 5

This is a quantitative defect hemoglobinopathy

Answer 5

Thalassemia

Question 6

Hemoglobin structure

Answer 6

Heme - 4 Fe atoms surrounded by pyrope ring
Globin - Each ring attached to globin

Question 7

Hgb A1

Answer 7

alpha 2 beta 2
97% of hemoglobin

Question 8

Hgb A2

Answer 8

alpha 2 delta 2
<3% of hemoglobin

Question 9

Hgb F

Answer 9

alpha 2 gamma 2
<2% of hemoglobin

Question 10

How can gene mutations affect globin chains?

Answer 10

Deletions or substitution of amino acids

Question 11

Mutations of globin chains can lead to

Answer 11

Dysfunctional hemoglobins that may or may not be clinically silent

Question 12

What does the efficiency of variant globin chains look like?

Answer 12

Less efficient, see more hgb A1 in heterozygotes than variant hemoglobin

Question 13

Almost all clinically important globin mutations are where?

Answer 13

Beta chain

Question 14

If gamma chain abnormalities were present, what would happen?

Answer 14

Fetal death, incompatible with life

Question 15

Delta chain abnormalities are present, what would happen?

Answer 15

Unimportant because Hgb A2 is <3%

Question 16

How many copies of defective beta globin chains would one need to have to see disease?

Answer 16

4 copies of alpha chain genes (2 from mom 2 from dad), so more copies are required to see disease

Question 17

Why is beta chain defect so important?

Answer 17

HgbA1 is the most abundant

Question 18

Most common lethal mutation in humans

Answer 18

Hemoglobinopathies

Question 19

Hemoglobinopathies are concentrated in what countries?

Answer 19

Africa
Mediterranean basin
Southeast Asia
Heritages from those countries

Question 20

How were hemoglobinopathies named initially?

Answer 20

Letters of the alphabet
Hgb A for adult, F for fetal, M for methemoglobin, S for sickle cells.

Question 21

How are hemoglobinopathies named now?

Answer 21

Which globin chain is affected and what amino acid has changed
(Hgb S = alpha2 beta2 6glu–>val)

Question 22

Heterozygous

Answer 22

trait

Question 23

Homozygous

Answer 23

Disease or anemia

Question 24

Most prevalent hemoglobinopathy world wide

Answer 24

Hgb S

Question 25

Where is the substitution made on Hgb S?

Answer 25

Valine instead of glutamic acid
6th position of the beta chain

Question 26

Homozygous notation for Hgb S

Answer 26

Alpha 2 Beta 2 6 glu –> val

Question 27

Hgb S notation for heterozygous

Answer 27

alpha 2 beta 1 beta 1 6 glu –> val

Question 28

What is the theory surrounding Hgb S?

Answer 28

Heterozygous state against P. falciparum malaria

Question 29

Hemoglobin C substitution

Answer 29

Glutamic acid –> Lysine substitution
6th position of the beta chain

Question 30

Homozygous notation for Hgb C

Answer 30

alpha 2 beta 2 6 glu –> lys

Question 31

Heterozygous notation for Hgb C

Answer 31

alpha 2 beta 1 beta 1 6 glu –> lys

Question 32

Geographic Association with Hgb C

Answer 32

same as Hgb S

Question 33

Why is Hgb C prevalent in the same populations as Hgb S?

Answer 33

thought to assist with malaria resistance

Question 34

Homozygous Hgb S

Answer 34

Hemoglobin SS
Sickle Cell Anemia

Question 35

How much hgb A1 is produced in Hgb SS?

Answer 35

None

Question 36

What percent of African descendants in the US have Hgb SS

Answer 36

0.3-1.3%

Question 37

Heterogynous Hgb S

Answer 37

Hemoglobin SA
Sickle Cell trait

Question 38

What percentage of African descendants have Hgb SA

Answer 38

8-10%

Question 39

How does hemoglobin S function under normal oxygen tension?

Answer 39

Normally