9: Haemogobinpathies

Question 1

Hemoglobin

Answer 1

the major functional protein in red cells and carries oxygen throughout the circulation

Question 2

Hemoglobin structure

Answer 2

a tetramer consisting of an alpha like globin chain and a beta like globin chain folded around a haem porphyrin center

Question 2

what are the two main groups of inhertied disorders of hemoglobin

Answer 2

• disorders of hemoglobin structures
• disorders of hemoglobin synthesis, the thalassemia’s

Question 2

during pre-natal life where does hematopoiesis happen

Answer 2

begins in the yolk sac, shifts to the liver, spleen and then bone marrow

Question 3

during post-natal life where does erythropoiesis happen

Answer 3

primarily in the bone marrow

Question 4

what are the two globin gene structures

Answer 4

alpha like cluster on chromosome 16
beta like cluster on chromosome 11

Question 5

Clinical syndromes associated with structural Hb variants

Answer 5

• Haemolytic anaemia
• Cyanosis
• Polycythaemia

Question 6

Haemolytic anaemia

Answer 6

unstable Hb
red blood cells are excessively fragile and break up causing anaemia and jaundice

Question 7

cyanosis

Answer 7

blue colour to skin and mucous membranes
Hb releases oxygen but remains in reduced form

Question 8

polycythaemia

Answer 8

excessive red blood cells which retain oxygen and do not release oxygen into tissues

Question 9

sickle cell anaemia

Answer 9

• autosomal recessive disorder
• red blood cells become more fragile and break up
• chronic anemia sickling crisis due to blockage of small blood vessels with fragmented red cells
• common in west Africa, Caribbean and African Americans

Question 10

treatment of sickle cell disease - acute crisis

Answer 10

pain relief
hydration

Question 11

treatment of sickle cell disease - chronic management

Answer 11

vaccination
prophylactic antibiotics
blood transfusion
hydroxyurea

Question 12

Thalassaemia

Answer 12

a group of genetic blood disorders when the body does not make enough hemoglobin which is a protein in red blood cells that carries oxygen

Question 13

Alpha thalassaemia

Answer 13

caused by the underproduction of alpha globin from alpha globin gene cluster on chromosome 16

Question 14

what does the severity of Alpha thalassaemia depend on

Answer 14

how many of the four genes are affected

Question 15

beta thalassaemia

Answer 15

underproduction of beta globin gene on chromosome 11

Question 16

where is alpha thalassaemia common

Answer 16

South East Asia

Question 17

where is beta thalassaemia common

Answer 17

Mediterranean

Question 18

what does the severity of Beta thalassaemia depend on

Answer 18

the nature of the gene mutations and whether one or both of the beta globin genes are affected

Question 19

deletion of all four alpha globin genes - what condition does it cause

Answer 19

• causes condition called Hb Bart’s
• most severe form of alpha thalassemia

Question 20

deletion of all four alpha globin genes - symptoms

Answer 20

babies with the condition are usually still born or die shortly after birth due to severe anaemia and heart failure
usually found in Asia

Question 21

deletion of 3 alpha globin genes - what does it cause

Answer 21

Haemoglobin H disease

Question 22

deletion of three alpha globin genes - why do the symptoms happen

Answer 22

People with Haemoglobin H disease only have one alpha globin that works properly.
To compensate for the lack of alpha chains the body starts to produce more beta chains, which form beta4 tetramers. These abnormal haemoglobins are less effective at transporting oxygen compared to normal haemoglobin.

Question 23

deletion of three alpha globin genes - symptoms

Answer 23

jaundice
growth delays
anemia

Question 24

deletion of two alpha globin genes

Answer 24

• alpha thalassemia
• mild, may not cause symptoms
• do not require blood transfusions

Question 25

deletion of 1 alpha globin gene

Answer 25

• very mild condition
• individual still produces enough alpha globin genes to form functional hemoglobin molecules

Question 26

what do repeated transfusions result in

Answer 26

premature death due to the complications of iron overload despite iron chelation therapy

Question 27

alpha beta thalassemia

Answer 27

deletion of both the alpha and beta globin chains on chromosome 11
surprisingly mild amaemia due to compensatory increased production of gamma globin chains