Each of us carries in our DNA genetic material that tells our body everything it needs to know about producing the enzyme Alpha-1 Antitrypsin (AA).
We each receive two copies of the AA gene. Each copy is from one of our parents. The copies are represented by letters:
MM
SS
ZZ
SZ
MS
Each letter represents instructions that tell our body how much AA to make:
M
"Make a normal amount"
S
"Make some, but not enough"
Z
"Make a very TINY amount"
Null or Zero
"Make none"
The combination of letters indicates whether or not our bodies produce AA normally.
NORMAL
MM
CARRIER
MS
MZ
AA DEFICIENT
SS
SZ
ZZ
Null
People who do not have AAD, but can give it to their children are called carriers. They have an "M" and some other letter. The one "M" makes their livers produce AA normally. Their kids might inherit the other letter, though; that is what makes these parents carriers.
Consider the following illustration:
People who DO have AAD do not have an "M". The severity of their condition is represented by the letters in their pi type.
For instance:
People with an SS are less likely to experience complications than someone with an SZ.
People with an SZ are less likely to experiences complications than someone with a ZZ.
People with an SS rarely experience complications.
People with ZZ have a very strong likelihood of experiencing complications.
People with SZ are somewhere in the middle.
Where they are in the middle depends on a number: their serum level
| Phenotype | Frequency (in population) (2) | mg/dl (Commonly Quoted Levels) | uM* (True Levels) | Emphysema Risk |
| Pi*MM | 90% | 150-350 | 20-48 | No increase |
| Pi*MZ | 4% | 90-210 | 17-33 | No increase |
| Pi*SS | 1.5% | 100-200 | 15-33 | No increase |
| Pi*SZ | .2% | 75-120 | 8-16 | Mild risk |
| Pi*ZZ | .02% | 20-45 | 2.5-7 | High risk |
| Null-Null | very rare | 0 | 0 | High risk |
I am an SZ. One copy of my gene "makes some, but not enough" AA. The other copy "makes a very TINY amount".
When I was tested at two years old, my serum level was 54mg/dl. According to the above chart, that puts me closer to a ZZ than SZ as far as risk level goes. But keep in mind, that is according to this chart. (BTW, I got it from this website. Evaluate for yourself how credible it is)
We do not know what my serum level is today, or if it changes during the course of a lifetime. We really know very little for certain, and I can't stress that enough. All we know for sure right now is that I have it; everything else is guesswork until I see the doctor.
Above are Dad's AA test results. It appears he is an MM (M1, really.... there are many forms of each type. Bottom line, his is the "normal" type). We do not have Mom's test results. We do know she does not have AAD.
This presents a conundrum. Given the information I have just explained, we are wondering WHERE I got the S and the Z if Dad is an MM. The only way it makes sense is if Mom is also an SZ.... but she isn't, because she doesn't have AAD.
... and I have not read anything about this skipping generations.
Maybe I was wrongly "typed"?
Maybe my parents were?
Maybe my understanding is too simplistic, or drastically incomplete?
In any case, our hope is that we can get an explanation from my doctor on how I ended up with it and what it might do to my body over the next few decades.
Great post, Meghan. Very helpful and informative (though I still don't understand some of this!).
ReplyDeleteI remember this being a "puzzle" at the time of diagnosis and followup as well. I also remember a conversation where I said "oh, so it's like a tumbling gene" (changes through the development somehow) and either my understanding was affirmed or that just stuck in my head.
Perhaps I didn't have a "normal" test... I don't have those results (somewhere along the way I purged stuff and kept only what I thought was pertinent) and maybe I never did. I do think it will help if we can get your narrative summary from Children's Mercy.
What is a tumbling gene? I googled it but I didn't find anything.
ReplyDeleteWhen you say it 'changes through development' do you mean the *effects* of the gene change depending upon the stage of development? Or, that the gene itself changes? I don't think genes change...
"Tumbling gene" is not a medical term, it was just the way I was interpreting what was being explained to me. These are good questions to ask of your doc once you get established with him.
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