Hey GA tell me why aHUS for them and not me?
Oh hi again. Who is them?
Some of my family they have had aHUS and I have haven’t?
Well it depends on you and them? If them refers to two or more family members then it is likely that your family members have inherited a genetic mutation.
Is that in the complement thing you are always talking about ?
Well yes, but it could be in something else. Let’s stick to complement.
OK
Each person inherits something from the parents’ DNA , 50 % from each of their parents.
So?
So if one the parents has a genetic mutation which predisposes someone to aHUS then there is fifty fifty chance of them inherits that mutation.
What if that parent has never had aHUS?
It does not matter, an inherited mutation just makes them susceptible to aHUS not necessarily get it . I take it you have family members with aHUS but you have not had the illness.
Precisely I am told this happens a lot but why?
Well you may just have not had the disease yet , or you may never.
Never?
Yes, you may not have the genetic mutation as they do so you are not susceptible to aHUS.
But if you do there are other reasons which means that the disease does not penetrate into your family 100% of the time . For aHUS, penetrance into families is mostly incomplete.
What other reasons are there?
Well if you are susceptible you may not have experienced a triggering hit.
Wait what? Like my sister she had aHUS after giving birth, I cannot face that trigger .
Yes exactly. The pregnancy trigger is the biggest single cause of aHUS in women.
But my uncle had aHUS too.He was not pregnant. He was in hospital at the time for a minor procedure. He got an MRSA infection there. It led to complications including aHUS and he died. He was 75 years old.
Sorry to hear that but it goes to show that he had been susceptible for eight decades and probably had many triggering hits, but this was one too far.
Clearly. You said there may be other reasons.
I did but this may be difficult to explain.
Try.
Well here goes.Many people know about there being genetic mutations which make individuals susceptible to aHUS. As well as some if not all the things which can trigger off Complement into the uncontrolled state.
Yes.
What if I said that there might be other more common genetic differences , doctors call them polymorphisms or haplotypes.
They would.
Well what if these haplotypes could have a modifying influence too on whether the mutation could make the mutated complement part works or not.
That is a change from what we have been told
Yes but this can only apply on a case by case basis and would require genetic testing doing which is beyond what is routine these days.
Go on.
OK so say for a Complement Factor H mutation which family members share tests of the haplotypes show that those who have onset have one haplotype which put them at more risk of having aHUS and those that have not as yet have another haplotype which puts them at less risk. That could explain incomplete family penetrance.
What is it about such haplotypes that they could have such an effect?
Well it gets very complicated now. If just say that one haplotype “encodes” one part of CFH component which makes it bind strongly to another part C3b which it has to do to stop Complement getting out of control it could put the rare mutation at much less risk. But if another haplotype encodes another part of CFH which makes it bind weakly to C3b the it puts the individual at much more risk.
Wow!
I must stress that this is not universal. Each family would require specific genetic counselling on their specific genetic traits on why statistically some in their family do get and some may not get aHUS.
How likely is it that our family could get such genetic counselling?
Sorry but it would very unlikely for you to be told unless your family is part of a research study.
So we just carry on not knowing!
Yes but it is likely that you will live to a ripe old age and not get it. But if you do get it, for more and more people there are treatments which can control your Complement for you.
At least those who are the only ones with their mutation do not have worry about all this.
Those with what is called “sporadic” aHUS. They have a different worry. If they want to have a family . They may not pass on the genetic mutation but their partner may switch the “at risk” haplotype to the “protective” haplotype which their partner may have.
it’s a funny old disease is aHUS. Thanks GA
You said it! You are welcome.
Article No. 582
