Transcript THAL Intermedia - Thalassemia Dubai

Data from Dubai Thalassemia
Centre
Chromosome 11
-globin gene
Chromosome 16
-globin gene
An example of inheritance:
Marriage between two carriers
Red blood
cell
Oxygen from
lungs
Oxygen released
to tissue cells
Hemoglobin
molecules
Oxygen boded with
hemoglobin molecules
1. Homozygous or compound heterozygous
state for  thalassemia
a) Inheritance of mild  thalassemia
alleles
b) Co-inheritance of  thalassemia
c) Increased Hb F response
 Xmn1 –polymorphism
  promoter mutations
 Trans-acting HPFH genetic
determinants
2. Heterozygous state for  thalassemia
a) Co-inheritance of extra  globin genes
(/, /, /)
b) Dominantly inherited  thalassemia
(Hyperunstable  chain variants)
3. Compound heterozygous for  thalassemia
and  chain variants e.g. Hb E
4. Compound heterozygotes for  thalassemia
and HPFH .
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-Thalassaemia genotypes of
parents
HbF values in parents
Co-inheritance of  thalassemia
Age at presentation
Level of Hb at presentation
Level of Hb A
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All patients had:
Serial FBCs
Hb Electrophoresis (HPLC) &/ or IEF
Molecular characterization of alpha
genes ( Deletional and non-deletional)
Beta genes mutations &Xmn1
Clinical monitoring of any possible
complication
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o +
HbA:
HbF:
HbA2:
Decreased
Inc(80-90 %)
Variable
 + +
HbA:
HbF:
HbA2:
Decreased(>20%)
Inc(70-80 %)
N or Increased
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The mean age is 11 (3-33) yrs,
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Non-deletional alpha-gene mutation was
normal in all our patients.
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Most of pts have mild to moderate
thalassemic features.
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Average hemoglobin level : 8.5 g/dl.
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40% of patients had infrequent hemoglobin
drop needed blood transfusion.
600
500
509
400
82.52%
420
300
200
8.64%
44
100
8.84%
45
0
Total
BTM
No of pts
BTI
BMT
23%
44%
33%
severe mutation
mild mutation
mixed
70
60
62.5
50
40
30
20
10
37.5
25
15
0
no. of pts
%
male
female
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9 = IVS 1 - 5 (G-C) / IVS 1 - 5 (G-C)
4 = IVS 1 - 5 (G-C) / - 25 bp del
3 = IVS 1 - 1(G-C) / IVS 1 – 1(G - C)
1 = IVS 1 - 1 (G-T) / IVS 1 - 1 (G - T)
1 = -25 bp del / -25 bp del
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2= CD 26 (G-A) / Milder mutation
2= IVS 11–1 (G-C) / IVS 11 – 1
1= IVS 1-6 (T-C) / IVS 1-6 (T-C)
1= CD 27 (G-T) / CD 39 (G-T)
1= CD 26 (G-A) / IVS 1 – 130 (G-C)
2= VS 1-6 (T-C) / mild
2= IVS 1-6(T-C) / IVS II-848(C-A)
2 = Cd 8 (-AA) / Cd 8 (-AA)
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2= IVS 1 - 5 (G-C) / - 88 (C-A)
3= IVS 1 - 5 (G-C) / Poly A
2= IVS 1– 5 (G-C) / CD 26 (G-A)
1= IVS 1 – 5 (G-C)/
1= -25 bp del / CD 27 (G-T)
14
12
14
10
8
10
6
4
2
6
6
4
0
No. of pts
Homozygous severe
Hetero mild/severe
Hetero severe
Hetero mild/mild
Homo mild
IVS 1-5(GC) =19
6, 32%
9, 47%
4, 21%
Homozygous
With severe
With mild
-Thal. Status
18 severe - mutation
6 homozygous
-thal 3.7
4 heterozygous
-thal 3.7
8 normal
- thal
14
12
13
13
10
8
9
6
4
5
2
0
Never tx
Rarely tx
Total
Severe mut.
Freq. tx
Mild mut.
Planned tx
4/20 (20%) patients received blood
transfusion rarely
 4/4 (100%) are homozygous positive for
XmnI,
 2/4 (50%) are heterozygous for –3.7
alpha-gene mutation (alpha-thalassemia
trait)
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Xmn1
5-P/P
2- P/ - ve
14
12
10
13
No of pts
8
8
6
4
5
2
0
total
mild mutation severe mut.
1-Pt
a- Thal. Trait
2 PTS
SEVERE MUTATION
1 a-GENE DELETION
Xmn1-p/p
2 PTS
SEVERE MUTATION
N--gene
Deletional & nondeletional
N- Xmn1
Multifactorial
Delayed puberty
path. fracture
pregnancy
Thal. Features
0
0.5
1
1.5
2
2.5
3
Among the known factors affecting the
phenotypic severity in our pts.:
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Type of Beta mutation.
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The presence of alpha-gene defect.
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XmnI mutation (homozygous and hetero)
would ameliorate the clinical course.
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Two of our patients have severe mutation
with normal a-thal and normal Xmn1
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Further studies still needed to specify
other factors.
Al Wasl Hospital, Genetic and
Thalassemia Center, Dubai, UAE.
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Erol Baysal, PhD
Aref Chehal, MD
Maisam Bakir,MD
Essam Dohair, MD
Lab. Technicians
Nursing Staff
Abdulla Alkhayat.MD