Hi Well that was another aHUS Awareness Day. Are you aware that 40% of aHUS patients have no known genetic cause of their aHUS – they are idiopathic? They just don’t know why they have aHUS .
Yes for another year. Wow! 40% you say?
Yes
How do know? And do you know if they are aHUS patients?
I read it, so 60% have a genetic cause but some don’t but their doctors still say they have aHUS.
OK we can come back to what their doctors say. But first what about those with anti factor H autoantibodies are they idiopathic or genetic even though they are not strictly a genetic cause, more autoimmune.
Well I believe they are included with the ones whose genetic cause is known- so its genetic together with those with anti Factor H autoantibodies
Fine but I have heard that idiopathic aHUS can embrace 30% of patients and also 50% of patients.
Maybe, but 40% falls within that range.
So it is more like “around 40%” of aHUS patients are idiopathic not 40% exactly.
I guess its more a ball park figure , an approximate figure if you like.
Like the figures for the incidence and prevalence of aHUS patients.
What?
For another time, but no one knows how many aHUS patients there are and yet around 40% of them are idiopathic. Has it always been so and will it always be in the future.
I don’t know, what do you think?
I think before the first genetic cause in complement was found 100% would have been regarded as idiopathic. Once found it dropped below 100% as more were found. Idiopathic aHUS patients are an evolving cohort.
I heard that the first cause found was in Complement Factor H and that was nearly 30 years ago and yes since then other complement components have been found to have aHUS causing mutations, and other mutations have been discovered within them so the percentage would have fallen and the addition of aHUS patients with anti Factor H and others have reduced what were called idiopathic cases.
Yes and mutations in other systems too if they exclude aHUS patients from the idiopathic numbers but still add those patients are added to the total number of patients redefining aHUS scope. Are they? How are DGKE, Plasminogen, Cobalamin/B12, Thrombomodulin counted?
I dont know.
Well the first three are not part of the complement system and patients with those TMA causes do not respond to complement inhibitor treatment. So should not be in the calculation.
You did not say that about thrombomodulin.
Thrombomodulin is a part of the coagulation system and although it is not part of the complement system it can help with complement regulation. When it is genetically defective it can’t help. So should be included.
Like Anti Factor H autoantibodies I suppose when they don’t help. I don’t know whether there is a systematic retest of past aHUS patients who were deemed idiopathic.
Good point when was 40% first mentioned.
Ah good question let me look.
OK
I have got Carla Nester saying 40% in 2012. It was based on the US patients they knew at the time in USA were categorised into groups and one group was called “idiopathic”.
Let me see. She actually says between 35% and 40% of what they think is aHUS, and using the then current genetic testing technology. And only in the USA.
Oh yes that is right.
That was 13 years ago so since then more mutations have been found and newer technology is being used.
I guess so.
There is lot of “guesstimating” going on. So if it was possibly 35% in 2012, why is a 50% idiopathic figure still possible today?
Well NORD are still saying it on their website aHUS page and it was updated this year so it’s still current.
To be fair they hedge their bets with a range of between 30% to 50% are idiopathic. And this NORD page has been around since 2004 and last published in 2016.
They have a doctor help write the page for them.
There are references cited too, the latest published in 2015. Back then Brodsky was saying 40 to 50% . Maga, while studying USA aHUS patients, found 54%, idiopathic. But 54% of what?
We are getting nowhere here. Idiopathic percentages must be based on something which has fully up to date genetic screening scope, including all historically screened patients who were deemed idiopathic. As well as a fully and consistently defined cohort of aHUS patients.
Yes until then we don’t really know what proportion are idiopathic and if we did it would need revising when new genetic factors are discovered. I think by 2025 it is 25% who are idiopathic. My take is that about two thirds have a known genetic cause, around a tenth have anti factor H autoantibodies and and a quarter are currently idiopathic.
You think? Do you have evidence of that?
As much as anyone else. But I have data.
Are they idiopathic because their complement genetic cause has not been discovered or are there other non complement hampering conditions yet to be found?
Both.
Fair enough but why is it so important to know ?
Well you brought it up but it is important to those who have been genetically counselled as idiopathic and what is said to them about what might happen to them. Though the negative genetic results mean something when it comes to accessing and discontinuing complement inhibitor treatment, pregnancy and transplants implications ,and for others in the family.
Could it also be seen seen as a measure of aHUS genetic testing progress if fewer patients are deemed idiopathic? The science is closing a knowledge gap.
Maybe but it depends on the shake up when aHUS is renamed and how the new classifications distribute “aHUS” patients. It will all be up for grabs then. Current percentages will be meaningless.
There will be no aHUS and once assigned by doctors using the science, 100% of those designated genetic complement TMA will be in their groups, as will be 100% in another TMA group which have anti factor H autoantibodies and 100% of third group who have known complement cause of their TMA but their doctors will say they still have complement mediated TMA.
These three groups will look at their disease from different perspectives.
Maybe form into different social communities. Like HUS and aHUS patients did.
Article No 757
