Lecture 10 - Hemoglobinopathies

Question 1

The structure of Hb is ___ subunits: two alpha subunits encoded by HBA on chromosome ____ and two beta subunits encoded by HBB on chromosome ___.

Answer 1

4 subunits:
HBA - chromosome16
HBB - chromosome 11

Question 2

Hemoglobin content varies with _______.

Answer 2

developmental stage

Question 3

Which type of (general type of) hemoglobinopathy is a structural chain variant?

Answer 3

Qualitative

Question 4

What happens to babies with sickle cell disease at 6 months of age?

Answer 4

Enough Beta S that it starts to sickle

Question 5

Which specific type of sickle cell crisis is a transient condition marked by the sudden increased lysis of RBC?

Answer 5

acute anemic crisis

Question 6

Which specific type of sickle cell crisis is a transient condition marked by the sudden disappearance of erythroblasts from the bone marrow?

Answer 6

acute aplastic crisis

Question 7

In sickle cell disease, the Beta subunit of HBB has a __________ mutation on chromosome 11.

Answer 7

missense mutation (GAT to GTG)

Question 8

What are the three classes of structural chain variants in SCD (usually caused by point mutations in one of the globin genes)?

Answer 8

1. Variants that cause hemolytic anemia
2. Variants with altered oxygen transport
3. Variants that cause Thalassemia

Question 9

What are the three types of hemoglobinopathies?

Answer 9

1. Qualitative (structural chain variants)
2. Quantitative (disrupt SYNTHESIS of globin chains)
3. Regulatory (impair switching of gamma-globin to beta-globin synthesis)

Question 10

Which of the 3 general types of hemoglobinopathies impairs switching of gamma-globin to beta-globin synthesis?

Answer 10

Regulatory hemoglobinopathy

Question 11

Which of the 3 general types of hemoglobinopathies disrupts SYNTHESIS of globin chains?

Answer 11

Quantitative hemoglobinopathy

Question 12

What disorder is caused by reduced synthesis or stability of HBB or HBA?

Answer 12

Thalassemia - sometimes described as the most common human single gene disorder

Question 13

alpha-Thalassemia is usually caused by _______ mutations.

Answer 13

deletion

Question 14

beta-Thalassemia is usually caused by _______ mutations.

Answer 14

point

Question 15

What are the two main types of alpha-Thalassemia?

Answer 15

1. Hydrops Fetalis (complete absence of a-chain in utero)

2. HbH disease (excess of Beta chains)

Question 16

What are the two main types of beta-Thalassemia?

Answer 16

1. Thalassemia major (absence of B-chain)

2. Beta+ thalassemia (some B-chain produced)

Question 17

Carriers of one Beta-thalassemia allele have:

Answer 17

Thalassemia minor

Question 18

The most physiologically important enzyme is:

Answer 18

methemoglobin reductase

Question 19

What enzyme maintains the heme iron in a reduced state?

Answer 19

methemoglobin reductase

Question 20

Cytochrome B5 reductase deficiency is an autosomal recessive disorder that falls into what class of structural chain variants?

Answer 20

Variants with altered oxygen transport

Question 21

Hemoglobin S is discovered by electrophoresis in a man who was skiing when he complained of severe skeletal pain and fever. Was the solubility of the HbS increased or decreased in the deoxygenated state?

Answer 21

HbS has decreased solubility in deoxygenated state

Question 22

Most alpha-thalassemias involve deletions of alpha-chain genes because of:

Answer 22

non-homologous cross over

Question 23

The major abnormal form of hemoglobin that accumulates in a fetus with the severe form of alpha-thalassemia is composed of:

Answer 23

A tetramer of 4 gamma-subunits

Question 24

Severe B-thalassemia may not become clinically apparent until a child is several months old because:

Answer 24

the gamma- to beta-globin switch is not complete until several months after birth

Question 25

Sickle cell disease can be caused by:

A) Loss or reduced synthesis of HBB
B) Loss or reduced synthesis of HBA
C) A compound heterozygote carrying HBS and a nonsense mutation in HBA
D) A compound heterozygote carrying HBS and a nonsense mutation in HBB

Answer 25

D.

Note: thalassemia disorders are caused by A&B - loss or reduced synthesis of HBA or HBB.