3. Haemoglobinopathies and Thalassaemia Flashcards
(118 cards)
1
Q
how many types of Hb are found in human blood?
A
3
2
Q
what are the 3 types of Hb found in human blood?
A
HbA
HbA(2)
HbF (foetal)
3
Q
on which Ch is the alpha globin gene?
A
16
4
Q
on which Ch is the beta, gamma, delta globin gene?
A
11
5
Q
how many copies of the alpha gene do we have?
A
2 on each chromosome - 4 in total
6
Q
how many copies of the beta, gamma, delta globin gene do we have?
A
2 of each
7
Q
after 3-6 of birth, what does HbF change into?
A
HbA
8
Q
what occurs in terms of genes in the transfer of HbF into HbA?
A
gamma is replaced by beta
9
Q
what is a haemoglobinopathy?
A
a mutation in the globin genes which give rise to different types and amounts of Hb
10
Q
2 types of haemoglobinopathy
A
thalassaemia and structural variant
11
Q
what does the mutation in thalassaemia result in?
A
functional but reduced/no synthesis of globin genes
12
Q
what does the mutation in the structural variant result in?
A
non-functional globin genes
13
Q
is the defect in thalassaemia quantitative or qualitative?
A
quantitative
14
Q
is the defect in structural variant quantitative or qualitative?
A
qualitative
15
Q
name the 4 most common structural variants of Hb?
A
SCED
16
Q
what type of mutation occurs in SVHb?
A
point mutation within globin genes - usually AA substitution
17
Q
which SVHb is most prevalent in punjab?
A
HbD
18
Q
which SVHb is most prevalent in south east asia?
A
HbE
19
Q
which SVHb is most prevalent in west + central africa?
A
HbC
20
Q
which 4 places is HbS most prevalent?
A
- tropical africa
- afro-caribbean
- south mediterranean
- central india
21
Q
which disease is caused by HbS?
A
sickle cell disease
22
Q
what is glutamic acid replaced with in HbC, and at what position?
A
lysine - position 6
23
Q
what is glutamic acid replaced with in HbE, and at what position?
A
lysine - position 26
24
Q
what is glutamic acid replaced with in HbD, and at what position?
A
glutamine - position121
25
which 2 SVHb cause mild haemolytic anaemia?
D and C
26
which SVHb results in an enlarged spleen?
HbC
27
what type of anaemia is caused by HbE?
mild microcytic hypochromic
28
what disease does the Hb trait protect against?
malaria
29
which is the most frequent SVHb?
HbS
30
where does the mutation occur in Sickle cell disease - at what point - what occurs?
in one or both of the beta genes. glutamic acid is replaced by valine in position 6.
31
what causes the change in shape to sickle in HbS?
HbS is less soluble when deoxygenated compared to HbA
32
3 predispositioning factors of SCD?
1. hypoxia
2. acidosis
3. increased body temperature
33
when can sickling be reversed?
after reoxygenation
34
when is sickling irreverssible?
after repeated cycles of oxygenation and deoxygenation
35
describe genes in heterozygous SCD. how many beta genes are affected?
Hb A + Hb S - only 1 affected
36
describe Hb and RBC levels in heterozyous SCD
normal
37
describe 3 sxs in heterozyous SCD
1. asymptomatic
2. haematuria
3. renal papillary necrosis
38
in what 3 conditions must patients with heterozyous SCD be carefully observed?
1. high altitude
2. pregnancy
3. anaetheesia
<40% oxygen
39
what type of anaemia is caused by homozygous SCD?
severe haemolytic
40
the clinical expression of homozygous SCD is variable and can lead to one of three outcomes; which are
1. shortened lifespan
2. normal life
3. severe crises
41
name 5 clinical features of homozygous SCD
1. priapism
2. kidney infections
3. pulmonary hypertension
4. susceptability to infections
5. retinopathy
6. ulcers of lower leg
7. dactylitis
8. enlarged spleen
9. liver damage
10. gallstones
11. severe crises
42
why do gallstones form in homozygous SCD?
haemolysis causes breakdown of RBC and build up of bilirubin
43
name 4 types of crises
1. haemolytic
2. vaso-occlusive
3. visceral sequestration
4. aplastic
44
what 3 things precipitate vaso-occlusive crises?
1. deoxygenation
2. dehydration
3. infection
45
which 4 places do vaso-occlusive crises occur?
brain, spleen, lungs, bones
46
what is visercal sequestration crises caused by?
accumulation of sickle cells in an organ
47
what syndrome does visercal sequestration crises lead to?
sickle chest syndrome
48
3 types of visercal sequestration crises
splenic, hepatic, girdle
49
which type of visercal sequestration crises occurs in infants?
splenic
50
2 causes of aplastic crises?
parvo virus
| folic acid deficiency
51
characteristics of aplastic crises?
sudden drop in Hb
| fall in reticulocytes
52
how to differentiate aplastic and haemolytic crises?
aplastic - fall in reticulocytes
| haemolytic - rise
53
characteristics of haemolytic crises
1. fall in HB
2. rise in reticulocytes
3. pain
54
lab findings of SCD
1. low Hb 60-90g/l
2. howell-jolly bodies
3. screening shows sickle +ve
4. Hb electrophoresis shows prescence of HbS (no HbA)
5. raised HbF
55
what are howell-jolly bodies?
remnants of DNA
56
which test differentiates between homozgous and heterozygous SCD; i) sickle solubility test ii) Hb electrophoresis iii) both
ii) Hb electrophoresis
57
what would show SCD in the sickle solubility test?
cloudy tube - shows HbS
58
prophylactic treatment of SCD
1. vaccination
2. folic acid
3. AB to reduce infection risk
59
why is folic acid given as a prophylactic treatment of SCD?
increase DNA and Hb production
60
treatment after crises of SCD
1. rest
2. rehydration
3. warmth
4. pain relief
61
what is the only cure to SCD?
transplantation
62
why is transfusion given in SCD?
RBC low
63
why is hydroxyurea given in SCD?
raise HbF
64
which 2 things have reduced the mortality rate of SCD
1. vaccination
| 2. awareness of acute splenic sequestratation syndrome to parents
65
what clinical features would arise from a combination o HbS and HbC genes?
same as homozygous HbS
66
what clinical features would arise from a combination o HbS and beta genes?
thalasseamia
67
2 causes of thalassaemia (T)
1. ineffective erythropoiesis
| 2. shortened RBC lifespan
68
what are the 3 classification criteria of T?
1. affected globin gene - alpha or beta
2. reduction in rate of synthesis of globin - total or partial
3. genotype - heterozygos or homozygous
69
where is T common?
malaria endemic areas
70
which continent is alpha T most common?
east asia
71
where is beta T most prevalent?
1. mediterraen
2. africa
3. greece
4. india
72
what type of mutation causes 95% of a-thalassaemias?
deletion - in 1 or both pairs of genes
73
what type of mutation causes 5% of a-thalassaemias?
point mutations
74
name 6 possible genotypes of alpha T mutation
1. normal
2. a+ heterozygote
3. a+ homozygote
4. a0 heterozygote
5. a0 homozygote
6. a+ a0 double heterozygote
75
genetic makeup of a+ heterozygote
a-/aa
76
what is the main ruling for a+
only affecting one of the chromosome on one gene
77
genetic makeup of a+ homozygote
a-/a-
78
genetic makeup of a0 heterozygote
--/aa
79
what is the main ruling for a0
affects both chromosomes on both genes
80
genetic makeup of a0 homozygote
--/--
81
a+ a0 double heterozygote
--/a-
82
which a-T genotype is incompatible with life?
--/-- a0 homozygote
83
which a-T genotype is a silent carrier?
a+ heterozygote a-/aa
84
which 2 a-T genotypes code for the A thalassaemia trait?
a+ homo a-/a-
| a0 hetero --/aa
85
which a-T genotype codes for the Barts hydrops foetalis disease ?
a0 homozygote --/--
86
what disease does the a0a+double heterozygote code for?
Hb H disease
87
which process will differentiate between a+ and a0 for alpha-T?
i) gel electrophoresis
ii) DNA analysis
iii) both
DNA analysis
88
which type of anaemia does alpha-T cause?
mild microcytic hypochromic
89
how to differentiate between a+ and a0 a-T?
mean cell Hb is lower in a0 than a+
90
which type and severity of anaemia does Hb H disease cause?
moderate-severe microcytic, hypochromasia anaemia
91
other clinical features of Hb H disease
hepatosplenomegaly
92
what does hypochromasia mean?
increase in central pallor of RBC
93
what does polychromasia mean?
high number of immature RBC
94
why is Hb H disease a problem?
it produces Hb H which is functionally useless
95
what is Hb Barts Hydrops Foetalis?
when only functionally usefull Hb barts and Hb H is formed - no normal is formed
96
what can prevent BHF?
genetic counselling
97
where is the mutation in b-T?
b globin gene
98
what type of mutation in b-T?
point
99
how are the types of b-T classified?
by severity of sxs
100
3 types of b-T
1. b-T trait
2. b-T major
3. b-T intermedia
101
describe where the mutation is in b-T trait and b-T major
```
trait = heterozygous = 1 beta globin gene
major = homozygous = 2 beta globin genes
```
102
which type of anaemia does b-T trait cause?
mild microcytic hypochromic
103
which type of anaemia does b-T major cause?
severe microcytic hypochromatic anaemia
104
describe the characteristics of RBC in b-T major
raised RBC count - nucleated RBC
105
skeletal deformities in b-T major are caused by.. (2)
- erythroid hyperplasia
| - expansion of BM volume
106
what does Hb electrophoresis show for b-T major?
increase in HbF and no HbA
107
Name 6 other diagnostic tests for b-T major
1. quantification of HbF
2. Column chromotography
3. Immunoassay
4. HPLC
5. Isoelectric focusing
6. DNA analysis
108
8 treatments for b-T major
1. Regular blood transfusions
2. Chelation therapy
3. AB
4. immunisation
5. Vit C
6. Splenectomy
7. Folic acid
8. BM transplant
109
why are regular blood transfusions offered for b-T major?
to maintain Hb levels ar 100-120 g/l - to suppress erythropoieses and prevent skeletal changes
110
what is a disadvantage of regular blood transfusions?
iron can build up - toxic
111
what can solve the problem of iron build up in the body?
chelation therapy
112
is b-T intermedia homozygous or heterozygous?
homozygous
113
what is the difference between b-T intermedia and major?
less severe sxs, diseases, - does not require blood transfusions
114
3 causes of BT intermedia?
1. inheritance of BT mutations
2. co-inheritance with a gene which increases the rate of gamma globin synthesis
3. co-inheritance with a-T
115
in what disease is hypersplenism prevalent?
bT intermedia
116
if sickle cells were detected in a blood film - what furhter tests would be conducted?
sickledex/sickle solubility test
| Hb electrophoressis
117
what does a cloudly sickle test tube indicate?
prescence of HbS
118
why does Hb electrophoresis need to be done after sickledex?
to find out if it is hetero or homozygous
