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Flashcards in HEREDITARY ANAEMIAS Deck (52):
1

Where is the world is sickle cell anaemia most prevalent?

Africa
Middle East
India

2

What are the two common haemoglobinopathies?

Sickling disorders
Thalassaemias

3

What are the two types of adult haemoglobin?

Hb A and Hb A2

4

How many pairs of peptide chain are contained within each haemoglobin molecule?

2

5

What are the two pairs of chain contained within Hb A?

Alpha and Beta

6

What are the two pairs of chain contained within Hb A2?

Alpha and Delta

7

What are the two pairs of chain contained within foetal haemoglobin?

Alpha and Gamma

8

What type of haemoglobin is most abundant in the adult bloodstream?

Hb A

9

What are the different forms of sickling disorder? For each one give the corresponding genotype.

Sickle cell anaemia - Hb SS
Hb SC disease
Sickle cell thalassaemia - Hb S/β+ thalassaemia
Sickle cell thalassaemia - Hb S/β˚ thalassaemia
Hb SD disease

10

Which chain is affected as a result of sickle cell mutation?

Beta chain

11

What types of haemoglobin will an adult heterozygote for sickle cell disease produce?

60% Hb A
40% Hb S
Small proportional increase in Hb A2

12

How does Hb S cause pathology in sickle cell disease?

The haemoglobin is normal as long as the oxygen saturation is high enough, however any drop in oxygen will lead to polymerisation of the chains and a subsequent change in shape of the red blood cells. This causes a sickle cell crisis.

13

Which chromosome contains the allele for the beta chain of haemoglobin?

Chromosome 11

14

Which chromosome contains the allele for the alpha chain of haemoglobin?

Chromosome 16

15

What types of haemoglobin will an adult homozygote for sickle cell disease produce?

Mostly Hb S
Small amount of Hb F (more than an unaffected individual)

16

What is a compound heterozygote with reference to sickle cell disease?

An individual with two alleles each with a different mutation in the gene for the β chain. For example Hb SC disease. This patient will have equal amounts of Hb S and Hb C.

17

What type of haemoglobin do compound heterozygotes who inherit the sickle cell gene from one parent and the β thalassaemia gene from the other predominantly make?

Mainly Hb S

18

What is the main clinical feature of sickle cell disease in heterozygotes (sickle cell carriers)?

No anaemia and mainly normal
Occasional renal papillary necrosis

19

What are the clinical features of sickle cell anaemia?

Painful crisis - widespread bone pain
Haemolytic anaemia
Low Hb concentration
High reticulocytes (precursor to erythrocytes)

20

What are the complications of sickle cell anaemia?

Gallstones (bile salt stones)
Chronic leg ulcers
Hand and foot syndrome (swelling of digits)
Aplastic crisis
Splenic sequestration crisis
Hepatic sequestration crisis
Lung disease
Infections - Strep pneumoniae, Haemophilus influenzae
Progressive renal failure
Aseptic necrosis of humoral/femoral head
Chronic osteomyelitis - sometimes due to Salmonella typhi

21

Infections from which organisms are people with sickle cell anaemia particularly susceptible to?

Encapsulated organisms - Strep pneumoniae, Haemophilus influenzae

22

Why are sickle cell anaemia patients particularly susceptible to infection by encapsulated organisms?

Autosplenectomy as a result of splenic crisis leads to reduced splenic function. As a result these organisms are not opsinized as efficiently.

23

What is the opsinization of encapsulated bacteria?

When they are covered in opsonin to increase the likelihood of being phagocytosed.

24

How is a definitive diagnosis of sickle cell anaemia made?

Electrophoresis of haemoglobin and the demonstration of the sickle cell trait in both parents.

25

How is sickle cell anaemia managed in areas of high prevalence?

Women are screened in early pregnancy and where there are two carrier parents, prenatal or neonatal diagnosis should be offered.
Babies with a diagnosis should receive penicillin daily and be immunised against S.pneumoniae, H.influenzae and N.meningitidis.

Painful crises are managed with adequate analgesics, hydration and oxygen.

26

In sickle cell patients, how are pulmonary sequestration crises managed?

Urgent exchange transfusion

27

What is the analgesic that should be used in a sickle crisis?

Opioids in conjunction with paracetamol or a NSAID

28

What are the important complications not to miss with the Hb SC variant of sickling disease?

Microvascular complications leading to retinal damage and blindness as well as necrosis of the humeral or femoral head and haematuria.

29

What are the two overarching types of thalassaemia and what is the difference?

α- and β-
Defined by which chain is synthesized inefficiently.

30

What disease are sickle cell anaemia and thalassaemia thought to be protective against?

Malaria

31

What is the difference between the β+ thalassaemia and the β˚ thalassaemia?

In β˚ thalassaemia, there is a complete loss of β chain output, whereas in β+ the output is partially reduced.

32

Where is thalassaemia most commonly found?

Africa, Mediterranean region, Middle East, South East Asia

33

How many different types of β thalassaemia mutation are there?

Over 150

34

What are the clinical features of Hb β/β˚ (heterozygotes for β thalassaemia)?

Asymptomatic
Hypochromic
Microcytic
Low Hb
Have twice as much Hb A2 as normal individuals

35

When do homozygotes of the β thalassaemia trait start to become symptomatic?

They develop severe anaemia in the first year of life.

36

What are the effects of being homozygous for β thalassaemia traits?

Deficiency of β chains
Excess alpha chains leading to damage of red cells
Hypertrophy of ineffective bone marrow leads to skeletal changes - eg skull bossing
Hepatosplenomegaly
Raised Hb F

37

What is skull bossing in the context of β thalassaemia?

Extramedullary haematopoiesis - the increased marrow activity in bones that otherwise would not be haemopoeitically active causes a deformity of the skull. An x-ray of the head would show a 'hair on end' sign.

38

What is thalassaemia intermedia?

Either when there is an inheritance of two β+ genes or of β thalassaemia and another β chain haemoglobinopathy. The most important of these is Hb E β thalassaemia.

39

How many genes for the α haemoglobin chain do we have?

4 - 2 on each chromosome 16

40

How many α genes must be knocked for α thalassaemia to be a problem?

1 and 2 are pretty much asymptomatic
3 will give Hb H disease
4 will give Hb Bart's hydrops fetalis syndrome

41

What is Hb Bart's hydrops fetalis syndrome?

This is when the fetus has no working haemoglobin α chain genes. The result is intrauterine death or stillborn at 25-40 weeks or death soon after birth.

42

What is Hb Bart's?

Tetramer haemoglobin of four gamma chains - found in Hb Bart's hydrops fetalis syndrome.

43

What is Hb H disease?

This is when three of haemoglobin α chain genes have been deleted leading to severe deficiency of α chain. The result is the formation of β4 tetramers (Hb H) which is unstable. This leads to chronic haemolytic anaemia.

44

What are the clinical features of Hb H disease?

Chronic haemolytic anaemia
Hb is 7.0-11.0 g/dL
Reduced MCV and MCH
Jaundice
Hepatosplenomegaly
Leg ulcers
Gallstones
Folate deficiency

45

What are the forms of α thalassaemia associated with mental retardation? What are their features?

ATR-16 - mild mental retardation
ATR-X - more severe mental retardation, skeletal deformities.

46

What does having α-thalassaemia trait mean?

αα/--
People are rarely symptomatic

47

How do you manage a baby with newly diagnosed β thalassaemia?

Continuous monitoring
Eventually will require lifelong transfusion - given washed red cell transfusions at monthly intervals
To prevent iron overload given overnight biweekly infusions of desferrioxamine or/and oral deferiprone together with vitamin C - need to monitor ferritin and liver iron levels
Hydroxyurea can raise levels of Hb F
Splenectomy may be useful in reducing number of transfusions required

48

What are the side effects of desferrioxamine?

Infection with Yersinia spp
Retinal damage
Acoustic damage
Reduction in growth

49

What are the side effects of deferiprone?

Neutropenia
Arthritis

50

What is glucose-6-phosphate dehydrogenase and what does deficiency in the enzyme (G6PD deficiency) cause?

There are two metabolic pathways in red cells. One is the anaerobic burning of glucose and the other is a protective pathway which generates reduced glutathione which is protective against oxidants. The deficiency of G6PD is an X-linked recessive condition which predisposes to haemolysis.

51

What are the clinical features of glucose-6-phosphotase dehydrogenase deficiency?

Neonatal jaundice
Sensitivity to broad (fava) beans
Haemolytic response to oxidant drugs

52

How are glucose-6-phosphotase dehydrogenase deficiency patients managed?

There is no specific treatment, other than avoiding known triggers.
In the acute phase of hemolysis, blood transfusions might be necessary, or even dialysis in acute kidney failure. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient and will live a normal lifespan in the recipient's circulation.