Treatment | Research | Lifestyle | Glossary | alpha-1 antitrypsin deficiency
In simple terms alpha-1 antitrypsin deficiency is an enzyme inhibitor deficiency caused by a damaged chromosome 14; thus it is genetic. The deficiency means that the blood is deficient of a chemical which should switch off the immune system when it has completed its work of dealing with an infection in the lungs. Because the immune system is not switched off, enzymes that are released continue to "gobble up" healthy lung tissue rather than just the infection and thus the internals of the lung is damaged causing emphysema. For a more technical explanation look at the following websites.
alpha-1 according to Net Doctor alpha-1 according to Wikipedia
alpha-1 and your family: a question to Dr Jayne Holme at ADAPT
This is a specific question put to Dr Holme at ADAPT but it gives an excellent explanation that can help us all. Reproduced with permission.
"I am still a little confused regarding A1AD and offspring. As you know I am PiZ, my wife was tested and her alpha-1-antitrypsin is normal. My understanding is that our children will have partially deficiency (PiMZ) which I believe means they are carriers.
The confusion is, if my sons marry a PiMM/PiMZ/PiSS/PiSZ/PiZZ or Null-Null what effect does this have on their children?
Dr Jayne’s Reply
Your assumption that your sons will be MZ if you are ZZ and your wife is MM is correct.
All offspring inherit one of 2 AAT genes from their mum and one of 2 AAT genes from their dad.
This means that there are always 4 potential outcomes (each of the four has an equal chance of happening ie. 25%)
So:
1. The child inherits the 1st gene from the dad and the 1st from the mum.
2. The child inherits the 1st gene from the dad and the 2nd gene from the mum.
3. 2nd gene from dad and 1st gene from mum.
4. 2nd gene from dad and 2nd gene from mum.
Therefore, as you say, your sons 1st gene is M and 2nd is Z.
Lets say his partner is MM (1ST gene M & 2nd gene M).
If we follow through the logic above, the possibilities would be:
1. MM
2. MM
3. ZM (or MZ as we call it)
4. ZM ( or MZ as we call it)
If you remember that there is a 25% chance that each of the 4 possibilities occurs, we can see there is overall a 50% chance of MM and a 50% chance of MZ.
Following the same process, if you sons partner was SZ:
1. MS
2. MZ
3. ZS (or SZ as we call it)
4. ZZ
Therefore there would be a 25% chance of the child being MS, 25% for MZ, 25% for SZ and 25% for ZZ.
Hopefully you will be able to work out the chances of the offspring having a certain outcome is your sons partner is all the other possibilities. If not, email again or call. I think the newsletter is due out soon, and there are also diagrams explaining this in there.
We know that ZZ or Z null or nullnull are at increased risk of emphysema. There is controversy about if SZ are. There is also controversy about is the MZ phenotype confers a slightly higher chance of asthma compared with the general population, but there is no increase in the risk of emphysema for MZ. The main issue would be screening their partners/children etc.
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