W2 LECT 3: Basic concepts in haemoglobinopathies

Question 1

3 Hemoglobin percentages within the RBC after 1 year of ife

Answer 1

HbA (α2 β2) : >95%
Hb A2 (α2 δ2) : 2.5–3.5%
HbF (α2 γ2) : <2%

Question 2

What are hemoglobinopathies?

Answer 2

Genetic disoders characterized by abnormal Hb producion, or reduced Hb synthesis, or a complete failure of Hb production

Question 3

Provide 2 main divisions of hemoglobinopathies

Answer 3

• Thalassaemias
• Hemoglobin varients

Question 4

Name and describe 2 types of thalasemmias

Answer 4

alpha thalassaemia: genetic disoder characterized by decreased alpha globin chain production

Beta thalassaemia: Genetic disoder characterised by decreased or complete absence of beta globin chain production

Question 5

Differentiate between the 2 divisions of hemoglobinopathies

Answer 5

Thalassaemias:

-reduced / absent globin
synthesis
- α, β, γ or δ thalassaemia
- Clinically imp: α & β

Hemoglob varients:
-Abnormal globin chain
synthesis
- α, β, γ or δ variants
- Clinically imp: α & β

Question 6

How many genes does alpha globin has?

Answer 6

4 genes on chromosome 16

Question 7

A feature of alpha thalassemia separating it from Beta thalassemia?

Answer 7

In alpha thalassemia there is deletion of alpha genes, not mutations

Question 8

Feature of B thalasemia differentiating it from alpha thalassemia

Answer 8

Beta globin gene (HBB), on chromosome 11 is mutated not deleted:
-Intra-genic mutations &
Promoter mutations

Question 9

alpha thalasemmias terminology

Answer 9

• 1 alpha genes deleted: a+
• 2 alpha genes deleted: a0

Question 10

Name the 4 types of alpha gene deletions we have

Answer 10

-1. single gene deletion
Clinically: Asymptomatic
-Hb: Normal
-MCV: Normal / borderline low
-HbA2: Normal

2. 2 gene deletion
   Clinically: Asymptomatic
   -Hb: N/borderline low
   -MCV: ↓ed
   -HbA2: N/↓ed
   -Mentzer index (MCV/RCC): <13
3. 3 gene deletion» HbH disease
   -Clinically: Effects of long term haemolysis
   Hb: Moderate anaemia → usuallycompensated
   MCV: ↓ed
    HbA2: ↓ed
4. 4 gene deletion
   -Clinically: Severe anaemia and hypoxia
   in-utero → hydrops fetalis
   Not compatible with life
   → death in 2nd / 3rd trimester

*hydrops fetalis_accumulation of fluid in two or more body compartments of a fetus or newborn

Question 11

HbH disease diagnostic procedures or techniques

Answer 11

• Clinical presentation (Anaemia,
  Jaundice, Complications)
   PB and reticulocyte smear (Peripheral Blood Smear)
   Hb Electrophoresis
   HPLC
   Genetic studies (PCR and Gene sequencing)

*The same diagnoses applies to Similar homozygous B thalassemia

Question 12

What are the clinical features of HbH disease?

Answer 12

Moderate anaemia (Hb ~8.5 g/dL)
usually compensated
-β4 (HbH) Does not function as O2 carrier

Complications of EVH:
-Fe overload
Bony abnormalities
Gall stones
Splenomegaly
Leg ulcers, etc

Question 13

What is the appropriate management of single and 2 gene deletion alpha thalasemmias?

Answer 13

• No treatment
• Genetic counselling
• Family studies (screening)

Question 14

How to manage HbH disease?

Answer 14

• Long term transfusion is usually not necessary
  Ad hoc red cell
  Fe chelation
• Ad hoc Red cell: administration of red blood cell transfusions on an as-needed basis, rather than on a scheduled or regular basis

Question 15

Name Two types of B thalassemia mutations

Answer 15

• Homozygous beta thalassaemia: B0 (absent production of B chain)

FEATURES:
Severe anaemia at 3-7 months
Transfusion dependent (uncompensated)
Complications-chronic EVH

• Heterozygous beta thalassemia: B+ (present, but reduced production of B globin )
  -Compensated haemolysis
  (Hb ~8.5g/dL)
  Therefore milder disease

FEATURES:
- Clinically: Asymptomatic
 Hb: Normal / borderline low
 MCV: ↓ed
 HbA2: ↑ed

Question 16

Normal B globin cluster

Answer 16

• 4 allelic γ globin genes
• 2 allelic β, δ and ε globin genes

Question 17

What are the complications of homozygous B thalassaemia?

Answer 17

Chronic EVH
 Fe overload
 Bony abnormalities
 Gall stones
 Splenomegaly
 Leg ulcers, etc

Question 18

Management of Homozygous β thalassaemia

Answer 18

• Red cell transfusion:
  β0/β0- red cell T/F every 3-4 weeks
  -Fe chelation, for there will be iron overload from Blood transf

β+/β+- Not transfusion dependent
 Fe chelation