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Data from Dubai Thalassemia Centre

BY: Dr. MOHD SALAH

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THALASSEMIA INTERMEDIA. Data from Dubai Thalassemia Centre . BY: Dr. MOHD SALAH. Chromosome 11 -globin gene. Chromosome 16 -globin gene. Chromosomes. INHERETENCE. An example of inheritance: Marriage between two carriers. Red blood cell. Oxygen from lungs. - PowerPoint PPT Presentation

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Page 2: BY:  Dr. MOHD SALAH

Chromosome 11-globin gene

Chromosome 16 -globin gene

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An example of inheritance:Marriage between two carriers

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Red blood cell Oxygen from

lungsOxygen released to tissue cells

Oxygen boded with hemoglobin molecules

Hemoglobin molecules

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1. 1. Homozygous or compound heterozygous state for thalassemia

a) Inheritance of mild thalassemia alleles

b) Co-inheritance of thalassemiac) Increased Hb F response

Xmn1 –polymorphism promoter mutations Trans-acting HPFH genetic

determinants

Page 6: BY:  Dr. MOHD SALAH

2. 2. Heterozygous state for thalassemiaa) Co-inheritance of extra globin genes

()

b) Dominantly inherited thalassemia(Hyperunstable chainvariants)

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 FBCsHb Electrophoresis (HPLC) &/ or IEFMolecular characterization of alphagenes ( Deletional and non-deletional) Beta genes mutations &Xmn1Clinical monitoring of any possiblecomplication

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HbA: Decreased HbF: Inc(80-90 %) HbA2: Variable

HbA: Decreased(>20%) HbF: Inc(70-80 %) HbA2: N or Increased

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The mean age is 11 (3-33) yrs,

Non-deletional alpha-gene mutation was normal in all our patients.

Most of pts have mild to moderate thalassemic features.

Average hemoglobin level : 8.5 g/dl.

40% of patients had infrequent hemoglobin drop needed blood transfusion.

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509

420

44 45

0

100

200

300

400

500

600

Total BTM BTI BMT

No of pts

82.52%

8.64%

8.84%

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44%

33%

23%

severe mutation mild mutation mixed

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2515

62.5

37.5

0

10

20

30

40

50

60

70

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) 25 bp del / CD 27 (G-T)

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14

4

6

10

6

02468

101214

No. of pts

Homozygous severe Hetero severe Homo mildHetero mild/severe Hetero mild/mild

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9, 47%

4, 21%

6, 32%HomozygousWith severeWith mild

IVS 1-5(GC) =19

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-Thal. Status

18 severe - mutation

8 normal - thal

4 heterozygous -thal 3.7

6 homozygous -thal 3.7

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13 13

5

9

0

2

4

6

8

10

12

14

Never tx Rarely tx Freq. tx Planned tx

Total Severe mut. Mild mut.

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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)

Xmn1

5-P/P 2- P/ - ve

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13

8

5

0

2

4

6

8

10

12

14

No of pts

total mild mutation severe mut.

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2 PTS

SEVERE MUTATION N-geneDeletional & nondeletional N- Xmn1

2 PTSSEVERE MUTATION 1 a-GENE DELETION Xmn1-p/p

1-Pt a- Thal. Trait

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0 0.5 1 1.5 2 2.5 3

Thal. Features

pregnancy

path. fracture

Delayed puberty

Multifactorial

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Among the known factors affecting the phenotypic severity in our pts.:

Type of Beta mutation.

The presence of alpha-gene defect.

XmnI mutation (homozygous and hetero) would ameliorate the clinical course.

Two of our patients have severe mutation with normal a-thal and normal Xmn1

Further studies still needed to specify other factors.

Page 30: BY:  Dr. MOHD SALAH

Erol Baysal, PhD Aref Chehal, MD Maisam Bakir,MD Essam Dohair, MD Lab. Technicians Nursing Staff Abdulla Alkhayat.MD

Al Wasl Hospital, Genetic and Thalassemia Center, Dubai,

UAE.

Page 31: BY:  Dr. MOHD SALAH