Haemoglobinopathies

Question 1

What are the functions of the globin chains in Hb?

Answer 1

keep haem soluble and protect from oxidation

Question 2

Which chromosome are alpha globin chains found on?

Answer 2

16

Question 3

How many alpha genes are there per chromosome?

Answer 3

2

Question 4

Which chromosome are beta like genes found on?

Answer 4

11

Question 5

How many beta genes per chromosome?

Answer 5

1

Question 6

How are genes on the chromsomes coding for globin arrranged?

Answer 6

in order of expression (eg, from 5 to 3 fetal to adult)

Question 7

By what age have adult levels of Hb been reached?

Answer 7

6-12 months of age

Question 8

What are haemoglobinopathies?

Answer 8

hereditary conditions affecting globin chain synthesis

Question 9

How are haemogloinopatheis generally inherited?

Answer 9

autosomal recessive

Question 10

What are the 2 main groups of haemoglobinopathy?

Answer 10

thalassaemias; structual haemoglobin variants

Question 11

What happens in thalassaemias?

Answer 11

decreased rate of globin chain synthesis restuling in impaired Hb production

Question 12

What are the two groups of thalassaemia?

Answer 12

alpha and beta

Question 13

What type of anaemia is seen with thalassamia?

Answer 13

microcytic hypochromic anaemia (inadequate Hb production)

Question 14

Why is there haemolysis in thalassaemia?

Answer 14

unbalanced accumulation of globin chains is toxic resulting in ineffective erythropoiesis

Question 15

What has allowed thalassaemia to flourish?

Answer 15

malaria

Question 16

What is a+?

Answer 16

deletion of one alpha gene from chromsome 16

Question 17

Waht is a0?

Answer 17

both alpha genes have been lost from chromsome 16

Question 18

what types of Hb are affected in alpha thalassaemia?

Answer 18

all forms- HbA; HbA2 and HbF as all contain alpha chains

Question 19

What is the alpha thal trait?

Answer 19

one or two genes missing out of 4

Question 20

What is HbH disease?

Answer 20

only one alpha gene left (a0/a+)

Question 21

What is Hb Barts hydrops fetalis?

Answer 21

no functional a genes

Question 22

What is seen with alpha thal trait?

Answer 22

asymptomatic and no rx needed- mild anaemia

Question 23

What is seen with HbH disease?

Answer 23

anaemia with very low MCV and MCH

Question 24

What is HbH?

Answer 24

excess beta chains forming a tetramer called HbH- cant carry oxygen

Question 25

What are the clinical features of HbH?

Answer 25

mod anaemia to transfusion dependent; splenomegaly; jaundice

Question 26

Where is HbH commonest globally?

Answer 26

SE Asia; middle east and mediterranean

Question 27

What is the majority of Hb seen at birth with Hb Barts hydrops fetalis syndrome?

Answer 27

Hb Barts (gamma tetramer) and HbH

Question 28

What are the clinical features of Hb Barts hydrops fetalis syndrome?

Answer 28

almost all die in utero- severe anaemia; cardiac failure; growth retardation; severe hepatosplenomegaly; SK and CVS abnormalities

Question 29

What is the difference between the mutations causing beta and alpha thalassaemias?

Answer 29

alpha is caused by deletions whereas beta are usually point mutations

Question 30

What type of Hb is affected in beta thalassaemia?

Answer 30

HbA

Question 31

What is seen with beta thalassaemia trait?

Answer 31

(b+/b or b0/b) asymptomatic- low MCV/MCH; raised HbA2

Question 32

What is beta thalassaemia intermedia?

Answer 32

b+/b+ or b0/b+ | moderate requiring occasional tranfusion

Question 33

What is beta thalassaemia major?

Answer 33

b0/b0 - svere, lifelong transfusion dependency

Question 34

When does beta thalassaemia major present?

Answer 34

6-24 months

Question 35

What does extramedullary haematompoisis cause?

Answer 35

hepatosplenomegaly; thickening of skull; organ damage; cord compression

Question 36

Why is regular transfusion required in beta thal major?

Answer 36

suppress ineffective erythropoiesis and inhibit over-absoprtion of iron

Question 37

Waht is the main cause of mrotality with treated beta thal major?

Answer 37

iron overload from transufion

Question 38

What are the consequences of iron overload?

Answer 38

impaired grwoth and puberty; DM; OP; cardiomyopathy; arrhythmias; cirrhosis; hepatocellular cancer; increased risk of sepsis

Question 39

How is iron overload managed?

Answer 39

iron chelation- desferrioxamine

Question 40

what is the mutation in sickling disorders?

Answer 40

point mutation in the beta globin gene substituting glutamine to valine producing bS

Question 41

What is the problem with HbS?

Answer 41

polymerises if exposed to low oxygen for a prolonged period which distorts the red cell damaging the RBC membraen

Question 42

Waht is the sickle trait?

Answer 42

one normal, one abnormal beta geen

Question 43

Why is there few clinical features of sickle trait?

Answer 43

HbS level too low to polymerise but may in severe hypoxia eg high altitude or under anaesthesia

Question 44

What is the inheritance of sickle cell anaemia?

Answer 44

autosomal recessive

Question 45

What is a sickle crisis?

Answer 45

episode of tissue infarction due to vascular occlusion

Question 46

Why do patients with sickle cell anaemia have chronic haemolysis?

Answer 46

shortened RBC lifespan

Question 47

Why do patients with HbSS have hyposplenism?

Answer 47

repeated splenic infarcts

Question 48

What is sickle cell disease?

Answer 48

compound heterozygosity for HbS and another beta chain mutation

Question 49

What is HbSC disease?

Answer 49

milder but increased risk of thrombosis

Question 50

What are the precipitatns of sickle crisis?

Answer 50

hypoxia; dehydration; infection; cold exposure; stress/fatigue

Question 51

What is the treatment of sickle crisis?

Answer 51

opiate; hydration; rest; oxygen; abx if infection; red cell exchange transfusion if severe

Question 52

What are the longterm effects of sickle cell anaemia?

Answer 52

impaired grwoth; pulmonary hypertension; renal disease; avascular necrosis; leg ulcers; stroke

Question 53

What is the long term mx of sickle cell anaemia?

Answer 53

hyposplenism so need to reduce infection risk; folic acid supplementation; hydroxycarbamide

Question 54

what is the function of hydroxycarbamide?

Answer 54

reduce severity of disease by inducing HbF production

Question 55

How can you quantify haemoglobins present?

Answer 55

high performance liquid chromatography or gel electrophoresis

Question 56

What does raised HbA2 on HPLC suggest?

Answer 56

beta thal trait

Question 57

What is the problem with HPLC in alpha thal trait?

Answer 57

is normal so DNA testing needed