[struggle]

You are asked to counsel a married couple expecting a baby. They are both fit and well, with no previous medical history. They both originate from South East Asia, and have no family history of birth abnormalities. There are no abnormalities on examination.

Results are shown below:
MALE

Hb 11.7 g/dl
Mean cell volume 70 fl
Mean cell haemoglobin 19 pg
Red cell count 5.6 x 1012/l
Haemoglobin electrophoresis normal

FEMALE

Hb 10.1 g/dl
Mean cell volume 68 fl
Mean cell haemoglobin 18 pg
Red cell count 6.0 x 1012/l
Haemoglobin electrophoresis normal

What condition is the fetus at risk from inheriting?
A. ß-Thalassaemia trait
B. Thalassaemia intermedia
C. Hydrops fetalis
D. Thalassaemia major
E. Homozygous haemoglobin E
can anyone explain?

 

[Mondoshawan]

C. Hydrops fetalis

Tough question! You have to know the genetics of the Thalassemias as well as know or look up normal lab values.

Both parents have α-Thalassemia minor. We know this because of their increased RBC count, decreased Hb concentration, and normal Hb electrophoresis:

• All hemoglobins have α-chains, so the relative proportion of hemoglobin blots on electrophoresis will be normal even though the Hb concentration is decreased.
• Any β-Thalassemia would show up as abnormal on Hb electrophoresis (decreased HbA and increased HbA2 and HbF)
• Silent carriers of α-Thalassemia (one gene out of four is deleted) do not have anemias
• Incidentally, deletion of three out of four alpha genes is called HbH anemia, and Hb electrophoresis is abnormal

Also, α-Thalassemia minor is different in Asian and Black populations! There are four genes for the alpha chain, two from the mother and two from the father.
In the Black population, the common α-Thalassemia minor is due to a trans deletion:

In the Asian population, it's due to a cis deletion:

Since our patients are Asian, their child has a 25% chance of having no Thalassemia, a 50% chance of having α-Thalassemia minor like the parents, and a 25% chance of having Hb Bart, a four-α-gene deletion that leads to hydrops fetalis and stillbirth.

The only one of these in the answer choices (and the "worst outcome" implied by the use of "risk" in the question stem) is C. Hydrops fetalis.

For more info on Thalassemias, read Rapid Review Pathology 3e pp. 201-3. Thalassemias are on p. 349 in First Aid 2011, but the difference between Black and Asian α-Thalassemia minor is not explained. The picture clippings above are from http://www.cooleysanemia.org/updates/pdf/Alpha_Thalassemia.pdf

 

[struggle]

thanks alott..this post is really helpful..now i can fully understand it.

 

[dr z]

.....

Thanks alot this post made Thalassemia genetics easy:happy: