Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab •...
Transcript of Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab •...
![Page 1: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/1.jpg)
Duffy Null Phenotype + Sickle Cell Disease + G6PD DeficiencyNiki LeeSt. Vincent’s Hospital Melbourne
2017 NICE, Brisbane
![Page 2: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/2.jpg)
Duffy Blood Group System (ISBT 008)
• Chromosome 1 – FY or DARC gene
• Multipass glycoprotein – passes red cell membrane 7 times
• Fya and Fyb
• Products of FY*A and FY*B allele• FY*X similar to Fyb but weak
• 3 phenotypes: Fy(a+b-), Fy(a+b+), Fy(a-b+)
• Polymorphic in most populations
• Other Fy antigens • Fy3/Fy5/Fy6 are high incidence
![Page 3: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/3.jpg)
Duffy Null
• 2 types of Duffy null – Fy(a-b-)• Those common in Africa (~100% certain regions)
• Fy*Null is identical to Fy*B - mutation in the promoter region• Alteration in GATA-1 sequence• Disrupts binding of the erythroid specific transcription factor, preventingthe expression in erythroid cells• Phenotypically null but not genotypically• Fyb antigens are expressed in lung, spleen, colon• Therefore will not be alloimmunized
• Other parts of the world – very rare• Total absence in the Fy gene• Resulting from deletion (frame shift) or nonsense mutation
• introduction of stop codon
• Protection against p. vivax and p. knowlesi
![Page 4: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/4.jpg)
GATA-1
![Page 5: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/5.jpg)
Normal Haemoglobinhttps://allaboutblood.com/category/blood-cells/erythrocytes/haemoglobin/
HbA: α2β2 >96%
HbA2: α2δ2 2.2 – 3-2%
HbF: α2Υ2 <1%
Adult haemoglobin
![Page 6: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/6.jpg)
Haemoglobin Variants
• Due to point mutation in the haemoglobin gene• Haemoglobinopathies
• Hb S, C, DPunjab, E, Oarab
• Detected by electrophoresis and chromatography techniques
• Hb S• Relatively common• High significance due to sickling• Result from glutamic acid – valine replacement in pos.6 in the β globin gene• Poor solubility in deoxygenated blood and can polymerize within the red cells
![Page 7: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/7.jpg)
Sickle Cell Disease
• Collective name for a group of conditions• Common in Africans but can be seen in Indians, Arabics and Greeks
• Homozygous sickle cell anaemia (SS)• Moderate to severe haemolytic anaemia• Sickle cells• Vascular occlusion leading to organ damage• Clinical severity may be variable
• Sickle cell trait (AS)• Heterozygous state is very common• No clinical abnormalities• Sickle cells only at high altitude and low O2 pressure
![Page 8: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/8.jpg)
Interactions
Hb Genotype Name Clinical symptoms
S βA/βS
βS/βSSickle cell traitSickle cell anaemia
NoneSevere haemolytic anaemia, vaso-occlusive episodes
Compound Hb βS/βC
βS/βD Punjab
βS/βO Arab
βO thal/βS
Β+ thal/βS
SC disease
SD diseaseSO diseaseSickle-β0 thal
Sickle-β+ thal
Mild anaemia, some vaso-occlusive episodes
Sickle cell anaemia
Mild sickle cell disease
![Page 9: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/9.jpg)
G6PD Deficiency
• Sex linked in the X chromosome• Many variants, 2 most common types
•Mediterranean type – very low enzyme activity, may lead to favism •A- type – In West Africans and US, sensitive to primaquine
• Susceptible to haemolysis - oxidative drugs• Hemizygous in males readily detectable (XY)• Heterozygous in females, harder to detect (XX)
• rarely homozygous
• Clinical syndromes:• intravascular haemolysis
![Page 10: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/10.jpg)
Case
•30 y.o female
•RAN 18/40
•HE performed as per MHW Thal programme
![Page 11: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/11.jpg)
FBE
31/4018/40 33/40 36/40
![Page 12: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/12.jpg)
CE electropherogram
• Likely βS/βS or β0/βS
No Hb A Not typical SS,
lower Hb S%
![Page 13: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/13.jpg)
Normal CE
![Page 14: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/14.jpg)
Day/Month/Year Footnote to go here Page 14
Homozygous α 3.7 deletion
Homozygous S
![Page 15: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/15.jpg)
G6PD Assay
18/40 33/40
RETIC = 184 x 109/LG6PD = 0.75 IU/g Hb[5.2-13.4 IU/g Hb]
![Page 16: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/16.jpg)
R1r K-k+Kpa-, Jk(a+b+)
![Page 17: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/17.jpg)
![Page 18: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/18.jpg)
Conclusion
• Delivered a healthy baby
• Mother required minimal blood transfusion Hydroxyurea Ok to transfuse Fy(a-b+)
• Child’s phenotype, thalassaemia and G6PD status
![Page 19: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/19.jpg)
References
Day/Month/Year Footnote to go here Page 19
Human Blood Groups 3rd Edition, Geoff Daniels
The global prevalence of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis, Ella T. Nkhmo et. All, Blood Cells, Molecules and Diseases; Vol 42, Issue 3 May–June 2009, Pages 267-278
Sickle Cell Disease in sub-Saharan Africa, Michael DeBaun et. All; https://www.uptodate.com/contents/sickle-cell-disease-in-sub-saharan-africa
![Page 20: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/20.jpg)
![Page 21: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/21.jpg)
Introduction
• Background theory
Duffy blood group system and the null phenotype
Sickle cell disease
G6PD deficiency
• Case
• Questions
![Page 22: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/22.jpg)
Red Cell Structure
![Page 23: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/23.jpg)
Embden-Meyerhof Pathway/Krebs Cycle
No oxidative protection
![Page 24: Duffy Null Phenotype + Sickle Cell Disease + G6PD Deficiency...D C, S,•Hb Punjab, E, Oarab • Detected by electrophoresis and chromatography techniques S•Hb • Relatively common](https://reader030.fdocuments.us/reader030/viewer/2022040802/5e3b5eee6fe96d75e06e6208/html5/thumbnails/24.jpg)
Sickle Trait + α Thal Expected Values
Haemoglobinopathy Diagnosis, Barbara Bain