Haemoglobinopathy

Question 1

Explain the normal structure of adult haemoglobin

Answer 1

• 2 alpha globin chains
• 2 beta globin chains
• each chain has a haem group (porphyrin ring + iron)

Question 2

What chromosome is the alpha chain found in and how many copies?

Answer 2

• chromosome 16
• 2 genes per chromosome
• 4 per cell

Question 3

What chromosome are beta chains found in and how many copies?

Answer 3

• chromosome 11

- 1 copy per chromosome, 2 per cell

Question 4

What is unique about Hb production during lifespan?

Answer 4

• alpha globulin produced throughout

- beta globulin produced in 3rd trimester, reaching level 4-6mnths postnatal

Question 5

What is a haemoglobinopathy?

Answer 5

• inherited condition affecting globin chain synthesis

- autosomal recessive

Question 6

2 main types of haemoglobinopathies?

Answer 6

• thalassaemia (decreased rate of globin chain synthesis)

- structural haemoglobin variants (normal rate of production, abnormal chain)

Question 7

Define thalassaemia?

Answer 7

• normal chains
• abnormal production
• alpha thalassemia
• beta thalassemia

Question 8

Consequences of thalassaemia?

Answer 8

• microcytic hypochromic anaemia

- haemolysis

Question 9

Explain alpha thalassaemia?

Answer 9

• unaffected individuals have 4 normal genes
• trait = 1 or 2 genes missing = asymptomatic carrier
• HbH disease = only 1 alpha gene left
• Hb Barts hydrops fetalis = no functional genes left

Question 10

3 degrees of alpha thalassaemia?

Answer 10

• trait
• HbH disease
• Hb Barts hydrops fetalis

Question 11

Explain beta thalassemia

Answer 11

• point mutation within the gene
• reduced beta production (b+) or absent (b0)
• only seen in adult haemoglobin
• b trait
• b intermedia
• b major

Question 12

3 degrees of beta thalassemia

Answer 12

• b thalasemia trait
• b thalassemia intermedia
• b thalassaemia major

Question 13

Explain HbH disease

Answer 13

• only one copy of alpha globulin

- commonest in SE Asia

Question 14

Symptoms of HbH disease

Answer 14

• only 1 copy of alpha globulin
• jaundice
• splenomegaly
• Anaemias

Question 15

When does b thalassemia major typically present

Answer 15

• age 6-24mnths

- when HbF drops

Question 16

management of beta thalassemia major

Answer 16

• regular transfusion

Question 17

Consequences of an iron overload

Answer 17

• endocrine dysfunction
• cardiac disease
• liver disease

Question 18

Management of iron overload

Answer 18

• iron chelating drugs (desferrioxamine)

Question 19

Consequences of ongoing blood transfusion

Answer 19

• iron overload

Question 20

What causes sickle cell anaemia

Answer 20

• point mutation in codon 6 of the beta globulin
• glutamine substituted to valine
• produces Bs
• HbS causes red cell membrane damage

Question 21

What is sickle cell trait

Answer 21

• one copy of HbS

- Asymptomatic carrier state

Question 22

What defines sickle cell anaemia?

Answer 22

• 2 copies of HbS

- distorted cells - block microvascular flow

Question 23

Precipitants of a sickle crisis

Answer 23

• hypoxia
• dehydration
• stress

Question 24

Treatment of a sickle cell crisis

Answer 24

• analgesia
• hydration
• oxygen
• antibiotics
• transfusion

Question 25

Long term management of sickle cell disease?

Answer 25

• prophylactic penicillin
• folic acid supplementation
• hydroxycarbamide

Question 26

How are haemoglobinopathies diagnosed?

Answer 26

• FBC, Hb, red cell indicies
• blood film
• liquid chromatography

Question 27

What diagnosises beta thalasemia trait?

Answer 27

• Raised HbA2