3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Diagnóstico de hemoglobinopatíasHaemoglobinopathy diagnosis

María del Mar Mañú PereiraEritropatología – Red cell Lab

Hospital Clínic i Provincial de Barcelona

maria.manu@enerca.org

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Normal gen

Mutated gen

Inheritance Pattern

Sickle cell disordersAnemia falciforme

ThalassaemiaTalasemia

25%

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Haemoglobin species

Globin chains Period when normally present

A α2 β2 Major haemoglobin in adult life

A2 α2 δ2 Minor haemoglobin in adult life

F α2 Gγ2 o α2 Aγ2 Major haemoglobin in fetal life/

Minor haemoglobin in adult life

Locus α-globin (Cr 16)

5’ HS40 ζ ψζ ψα2 ψα1 α2 α1 θ 3’

Perutz 1962

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Locus β-globin (Cr 11)

5’ LCR ε Gγ Aγ ψβ δ β 3’

Haemoglobin species

Globin chains Period when normally present

A α2 β2 Major haemoglobin in adult life

A2 α2 δ2 Minor haemoglobin in adult life

F α2 Gγ2 o α2 Aγ2 Major haemoglobin in fetal life/

Minor haemoglobin in adult life

Perutz 1962

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

HbS, C, D y E

βX

β

Red cell

Membrane

Enzymes

Haemoglobin

Structural Haemoglobinopathies

Thalasaemias

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

α-thalassaemiaβ-thalassaemiaδβ-thalassaemia

β+

β

HbS, C, D y E

Red cell

Membrane

Enzymes

Haemoglobin

Structural Haemoglobinopathies

Thalasaemias

β

β0

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Father

Carrier HbS β- Tal δβ- Tal Hb Lep HbE HbO HbC HbD HPPF NP

Mother Hb S

β- TAL

δβ- TAL

Hb Lepore

Hb E

Hb OArab

Hb C

Hb D

HPPF

NP

High risk Moderate risk Non risk

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Isoelectricfocusing (IEF) Citrate Agar Electrophoresis

High Performance Liquid Cromatography (HPLC)

Capillary Electrophoresis (CE)

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

HPLC- Normal

2,5%

0,3%

85,3%

HbA α2β2 95-98%HbA2 α2δ2 <3.5%HbF α2γ2 <2.0%

F

A

A2

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

High risk Moderate risk Non risk

Father

Carrier HbS β- Tal δβ- Tal Hb Lep HbE HbO HbC HbD HPPF NP

Mother Hb S

β- TAL

δβ- TAL

Hb Lepore

Hb E

Hb OArab

Hb C

Hb D

HPPF

NP

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

40-45% HbS

Heterocygote S

β S

αα

αα

42,5%

57,5%

5’ LCR ε Gγ Aγ ψβ δ β 3’

F

A

A2

S

β

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Father

Carrier HbS β- Tal δβ- Tal Hb Lep HbE HbO HbC HbD HPPF NP

Mother Hb S

β- TAL

δβ- TAL

Hb Lepore

Hb E

Hb OArab

Hb C

Hb D

HPPF

NP

High risk Moderate risk Non risk

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

100% HbS

Homocygote S

β S

β S

αα

αα

96,4%

3,6%

F A??

A2

S

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Father

Carrier HbS β- Tal δβ- Tal Hb Lep HbE HbO HbC HbD HPPF NP

Mother Hb S

β- TAL

δβ- TAL

Hb Lepore

Hb E

Hb OArab

Hb C

Hb D

HPPF

NP

High risk Moderate risk Non risk

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Compound heterozygote S/ β0 , δβ0 o PHHF

100% HbSβ 0

β S

αα

αα

91,9%8,1%

F

A?? A2

S

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Compound heterozygote S/ β+

β+

β S

αα

αα>50% HbS

76,9%

23,1%

F

A A2

S

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

<35% HbS

Compound heterozygote S/ α-thalassaemia

β

β S

αα

α-

26,7%73,3%

A S

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Father

Carrier HbS β- Tal δβ- Tal Hb Lep HbE HbO HbC HbD HPPF NP

Mother Hb S

β- TAL

δβ- TAL

Hb Lepore

Hb E

Hb OArab

Hb C

Hb D

HPPF

NP

High risk Moderate risk Non risk

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

50% HbS 50% HbC

Compound heterozygote S/C

βC

βS

αα

αα

55,67%44,33%

CS

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Father

Carrier HbS β- Tal δβ- Tal Hb Lep HbE HbO HbC HbD HPPF NP

Mother Hb S

β- TAL

δβ- TAL

Hb Lepore

Hb E

Hb OArab

Hb C

Hb D

HPPF

NP

High risk Moderate risk Non risk

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

5’ LCR ε Gγ Aγ ψβ δ β 3’

HbA2 >3,4%

HbF > 2,0%

β-thalassaemia carrier

4,4%

4,9%

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Father

Carrier HbS β- Tal δβ- Tal Hb Lep HbE HbO HbC HbD HPPF NP

Mother Hb S

β- TAL

δβ- TAL

Hb Lepore

Hb E

Hb OArab

Hb C

Hb D

HPPF

NP

High risk Moderate risk Non risk

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

δβ-thalassaemia carrier

2,7%

8,3%

5’ LCR ε Gγ Aγ ψβ δ β 3’

HbA2 <3,4%

HbF 7-15%

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Father

Carrier HbS β- Tal δβ- Tal Hb Lep HbE HbO HbC HbD HPPF NP

Mother Hb S

β- TAL

δβ- TAL

Hb Lepore

Hb E

Hb OArab

Hb C

Hb D

HPPF

NP

High risk Moderate risk Non risk

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Compound heterozygote β0 / β0 , δβ0 o PHHF

0% HbAβ 0

αα

αα

94,8%2,3%

F

A2

β 0

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Father

Carrier HbS β- Tal δβ- Tal Hb Lep HbE HbO HbC HbD HPPF NP

Mother Hb S

β- TAL

δβ- TAL

Hb Lepore

Hb E

Hb OArab

Hb C

Hb D

HPPF

NP

High risk Moderate risk Non risk

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Heterocygote Hb Lepore

HPLC: HbA2 10-15%

Increased HbA2

Heterocygote HbE

HPLC: HbA2

>20%

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Father

Carrier αα/αα αα/α- αα/--

Mother αα/αα

αα/α-

αα/--

Alpha thalassaemia

High risk Moderate risk Non risk

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

α-thalasaemia- HbH

β

β

- -

- α

HbH

10,4%

0,9%

10,6%

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Genetic diagnosis

More than one deffect associated HbS/β-thal β-thal/ α-thal/ δβ-thal Unknown haemoglobinopathies Silent β-thal/ β++-thal

Father not available Rare Hb S variants with clinical manifestation

HbS Antilles/ HbS Oman Prenatal diagnosis Preimplantation genetic diagnosis (PGD)

3rd European Symposium on Rare Anaemias1st Spanish Thalassaemic meeting for patients and health professionals

Eritropatología- ENERCA

Dr Joan Lluis Vives Corrons Dr María del Mar Manú PereiraMontse CorbellaEstefanía GarcíaJessica AbadLaura Olaya Costa

Hospital Clínic i Provincial de Barcelonac/ Villarroel 170- Escalera 9 Planta 008036 BarcelonaTelf 932271739

Muchas gracias - Thank you very much - Moltes gràcies

maria.manu@enerca.org