![Page 1: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/1.jpg)
Clinical case
• A pregnant woman heterozygous for Hb S
• Her partner is tested for an haemoglobinopathy • Absence of HbA
• HbS 60%
• HbF 38%
• HbA2 2%
• Questions
![Page 2: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/2.jpg)
Couple Hb AS and HbSS with Hb F 38% and no clinical symptoms since birth. What to do next?
1. You test the sample with another technique of separation of the haemoglobin fractions
2. You call the gynaecologist to know the ethnic origin of the partner
3. You look at other biological results, in particular the complete blood count
4. You don’t know what to do in such situation
![Page 3: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/3.jpg)
Couple Hb AS and HbSS with Hb F 38% and no clinical symptoms since birth. Couple at risk of having a child with a severe sickle cell syndrome?
1. No, HbSHPFH and HbSdelta-beta°-thalassaemia are clinically harmless
2. It is mandatory to make the differential diagnosis between HbSHPFH and HbSdelta-beta°-thalassaemia
3. I don’t know
4. I don’t know and will send the couple to a geneticist
![Page 4: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/4.jpg)
Switch HbF HbA
4
![Page 5: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/5.jpg)
Mutations involved
5
BUT genuine HPFH should be defined as non-gene deletion related: no association with a reduced expression of the β-globin gene Example: Xmn-I polymorphism with enhancement of HbF expression only during erythropoietic stress (increase therapeutic effect of hydoxyurea)
![Page 6: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/6.jpg)
Heterocellular distribution of Hb F: non gene-deletion of HPFH
Human Molecular Genetics, 2009, Vol. 18, Review Issue 2 R217
Guidelines: Eur J Hum Genet. 2015; 23(4): 560.
• Hb F >5%, are associated with • δb or γδb-thalassaemia
heterozygotes (along with normal or low Hb A2 levels and reduced RBC indices)
• or hereditary persistence of fetal haemoglobin (HPFH).
![Page 7: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/7.jpg)
![Page 8: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/8.jpg)
« deletional HPFH »
• Most often • HPFH-2 and 1
• Pancellular distribution of F cells
• Hb F > 30-35%
• Haemoglobin level around the lower reference value
• MCV (> 18 y.o.) 75 ± 6 fl (F cells are larger than non F cells)
• Hb A2 normal or low
• No clinical sign (sickle cell disease or beta-thalassaemia)
![Page 9: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/9.jpg)
Offer prenatal diagnosis Eur J Hum Genet. 2015; 23(4): 560.
![Page 10: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/10.jpg)
Take home message
• HbF < 5% = most often not clinically relevant
• Harmless HPFH conditions • Beneficial effect in the presence of sickle cell disease (and thalassemia major)
• Doubt? • (Genetic counselling) Molecular analysis in a specialized laboratory
![Page 11: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/11.jpg)
Clinical case
• A pregnant woman heterozygous for Hb S
• Her partner is tested for an haemoglobinopathy • Absence of HbA
• HbS 60%
• HbF 38%
• HbA2 2%
• Questions
![Page 12: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/12.jpg)
Couple Hb AS and HbSS with Hb F 38%. What to do next?
1. You test the sample with another technique of separation of the haemoglobin fractions
2. You call the gynaecologist to know the ethnic origin of the partner
3. You look at other biological results and seek clinical data
4. You don’t know what to do in such situation
![Page 13: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/13.jpg)
Couple Hb AS and HbSS with Hb F 38% since birth. What to do next?
1. You test the sample with another technique of separation of the haemoglobin fractions
2. You call the gynaecologist to know the ethnic origin of the partner
3. You look at other biological results and seek clinical data
4. You don’t know what to do in such situation
![Page 14: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/14.jpg)
Couple HbAS and HbSS with HbF 38% and no clinical symptoms since birth?
1. It is certainly a hereditary persistence of foetal haemoglobin
2. It is certainly a delta-beta° thalassaemia
3. Molecular genetic analysis will give the diagnosis
4. You ask the advice of an expert in the field
![Page 15: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/15.jpg)
Couple HbAS and HbSS with HbF 38% and no clinical symptoms since birth?
1. It is certainly a hereditary persistence of foetal haemoglobin
2. It is certainly a delta-beta° thalassaemia
3. Molecular genetic analysis will give the diagnosis
4. You ask the advice of an expert in the field
![Page 16: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/16.jpg)
Couple Hb AS and HbSS with Hb F 38% and no clinical symptoms since birth. Couple at risk of having a child with a severe sickle cell syndrome?
1. No, HbSHPFH and HbSdelta-beta°-thalassaemia are clinically harmless
2. It is mandatory to make the differential diagnosis between HbSHPFH and HbSdelta-beta°-thalassaemia
3. I don’t know
4. I don’t know and will send the couple to a geneticist
![Page 17: Clinical case - Hôpital Erasme · 2016-11-25 · Clinical case •A pregnant woman heterozygous for Hb S •Her partner is tested for an haemoglobinopathy •Absence of HbA •HbS](https://reader035.vdocument.in/reader035/viewer/2022081611/5f0885ba7e708231d4226d59/html5/thumbnails/17.jpg)
Couple Hb AS and HbSS with Hb F 38% and no clinical symptoms since birth. Couple at risk of having a child with a severe sickle cell syndrome?
1. No, HbSHPFH and HbSdelta-beta°-thalassaemia are clinically harmless
2. It is mandatory to make the differential diagnosis between HbSHPFH and HbSdelta-beta°-thalassaemia
3. I don’t know
4. I don’t know and will send the couple to a geneticist