Inderited Disorders Of Haemoglobin

Question 1

2 major classes of inherited disorders of haemoglobin

Answer 1

Production of abnormal globin proteins
⬇️ output of globin genes

Question 2

HbS

Answer 2

Point mutation in codon 6 of beta globin gene
Substitution of glu -> val
Sickle shaped RBC

Question 3

What happens to HbS in Sickle Cell Anaemia?

Answer 3

HbS becomes deoxygenated - capable of reversibility polymerising w/ other HbS

Question 4

Sickle Cell Trait

Answer 4

Genotype AS
Conc of HbS ~ 40% of total Hb

Question 5

Sickle Cell Disorder

Answer 5

Genotype SS - most severe form of sickle cell disorder

Question 6

New Born Screening Programme for sickle cell disorder

Answer 6

Heel prick test at 5-8 days

Question 7

HbSC Disease

Answer 7

Less severe sickling of RBC
Bone complications
Haemolytic anaemia

Question 8

Clinically significant Hb variants

Answer 8

Hb C, D, O, E

Question 9

HbE homozygous & heterozygous

Answer 9

Homozygous - mild anaemia & cell survival
Heterozygous HbE & beta thalassaemia- more severe

Question 10

Metahaemoglobin

Answer 10

Substitution of histidine
Fe2+ oxidised to Fe3+

Question 11

Alpha Thalassaemia

Answer 11

Deficiency in alpha globin synthesis due to deletions of ≥1 genes

Question 12

Excess beta globin proteins may form ____ in alpha thalassaemia

Answer 12

HbH
Excess of HbH in RBC = formation of inclusion bodies which ⬇️ oxygen carrying capacity

Question 13

Silent Carrier State

Answer 13

Genotype -α/αα
Asymptomatic
2 common deletions of 3.7 & 4.2 kb

Question 14

α Thalassaemia Trait

Answer 14

• -/αα or -α/-α

Question 15

Haemoglobin H Disease

Answer 15

-α/- -
High levels of beta chains
Unpaired beta chains self assemble -> HbH
Moderate to marked anaemia

Question 16

Haemoglobin Barts

Answer 16

• -/- -
  Predominant Hb = tetramer of gamma chains = Hb Barts
  No oxygen carrying capacity. Oxygen starvation of foetal tissue
  Heart failure -> marked oedema

Question 17

α+

Answer 17

1 gene on both chromosomes

Question 18

α-

Answer 18

2 genes on same chromosome

Question 19

Beta thalassaemia

Answer 19

Deficiency of β synthesis due to point mutations & small insertions & deletions
Extremely insoluble α globin tetramers form -> affect membrane function & leads to premature RBC destruction in bone marrow & spleen

Question 20

Thalassaemia Major

Answer 20

Severe anaemia from 1st year. Requires blood transfusions
Bone marrow ⬆️ efforts to produce blood
Cortex becomes thin -> fracturing & distortion of bones in face & skull
Hepatosplenomegaly
Microcytic hypochromic RBCs

Question 21

Consequence of long term blood transfusions & how to treat

Answer 21

Accumulation of iron in organ
Iron chelation therapy

Question 22

Thalassaemia Minor

Answer 22

Heterozygous. 1 normal β globin gene
Generally asymptomatic

Question 23

Hereditary Persistence of Foetal Haemoglobin

Answer 23

Benign condition
10< HbF >30 % as adult
Deletion or mutation
Gamma globin gene remains to compensate for loss of HbA & HbA2

Question 24

Beta thalassaemia mutations usually involve (5)

Answer 24

Point mutations in promoter
Mutations in translation initiation codon
Point mutations in polyadenylation signal
Mutations leading to splicing
Nonsense mutation