Hi I don’t have the aHUS gene.
Hi That is good, but there is no aHUS gene that you have n’t got.
What do you mean there is no aHUS gene?
There is no gene called aHUS though some people say they don’t have “the gene”
But aHUS is genetic
Yes but it is the complement part of DNA where the genes are. It is where it specifies its complement components.
What do you mean ?
There are genes which create individual components of complement like the CFH or CD46 genes which make FH and CD46 proteins?
Yes I don’t have one of those genes then.
Yes you do we all them but some aHUS people say things like I don’t have the CD46 gene. They do, but the actual CD46 that it produces may have a fault in it?
The fault that causes aHUS
Not “the” fault but “a fault” there are many faults that can occur ,they are called mutations, significant variants or predisposing factors. Not all, lets stick to mutations, are pathogenic ( doctors speak for “causing” ) for aHUS. Just some.
Some?
Yes not all mutations disrupt the normal working of complement?
So I don’t have any mutations which caused my aHUS?
We will comeback to that. First of all mutations are created in different ways in “genetics speak” they can be missense , non sense and splice regions. Most aHUS pathogenic mutations are missense.
Genes can manufacture complete complement parts but have bits which don’t work as the should do because the genes have instructed a different version of that component which doesn’t work properly. Moving on to splice regions mutations the are in the DNA manufacturing process and can miss out parts of the instructions and produce incomplete component parts or none at all.
So
So there are mutations which mean the complement part isn’t fully working and others where the part is only partly made and not there at all to do its job.
But although I have the complement genes and nothing has been found to say they are not working, or even do not exist. I can have aHUS.
Weird isn’t it. It used to be said treatment for a suspected aHUS diagnosis should be started before genetic testing is done to confirm the diagnosis, A positive genetic test result would be a confirmation. But what of a negative result? Do you still have an aHUS diagnosis and has treatment continued?
Well yes my doctor says I have aHUS. So the confirmation is not needed.
I guess so but it is not the end of the matter.
Why not? I have my diagnosis and it is the same as those who have CFH or CD46 or C3 and the rest.
Yes but what did your genetic counsellor tell you I hope it was more than just that you have no genetic mutation.
It was my doctor who told me. Not who you said.
Genetic counselling about can be done by different people in different ways and with different advice. Sometimes not at all. Whilst the diagnosis is the starting point it also important to know what probably is going to happen to you in the future.
Probably?
Yes there are no certainties only percentages, which themselves are often within predicted ranges but these can influence things going forward. The same as for the rest of patients who have identifiable mutations. There are differences of prognosis ( what happens) for aHUS patients within each complement part and between each part. You have to be specific to get specific advice.
A genetic counsellor needs to know them and then see where you slot in.
Cant I just ask people who are just like me?
Yes of course but be specific because loose terms used make accurate comparisons difficult and misleading. Looking at all other patients feedback in their entirety would be essential. No one, unless they are related, will be the same as you.
Of course these days there is much on line to read and now AI can be asked to produce a genetic counselling like advice in plain language.
“Counselling like “
AI cannot give you medical advice but it can produce a script for you to talk your counsellor. But you know that.
So I have complement genes but no mutation has been found in them and knowing that can help predict what might happen to me going forward which may be different to someone with say a CFH or CD46 mutation. And AI can tell me what could happen but not give me medical advice.
Yes that’s about it!
Article No.769
Wait a minute while you are here …..
Why don’t viewers who have access to AI tools do their own “counselling like” report using a question like the one below and feedback whether it just tells you all you already know, or added something you didn’t know or if it was all news to you.
Provide a plain language genetic counselling like report for a patient diagnosed with aHUS with HERE ENTER YOUR GENE MUTATION OR JUST SAY NO MUTATION and what their prognosis may be.
Here is an example of counselling like report for a patient with a CD46 mutation:
Genetic Counselling Report for Atypical Hemolytic Uremic Syndrome (aHUS)
Patient Name: [Not specified; please insert as needed]
Date of Report: January 27, 2026
Diagnosis: Atypical Hemolytic Uremic Syndrome (aHUS) with a genetic variant in the CD46 gene (c.286+1G>C)
Dear Patient,
This report is designed to explain your diagnosis in simple terms, like a conversation during genetic counselling. It covers what aHUS is, what your genetic results mean, how it affects your health, what the future might hold (prognosis), and next steps. I’ll use everyday language and explain any medical terms. This is based on current medical knowledge, but remember, everyone’s situation is unique—please discuss this with your doctor for personalized advice.
What is Atypical Hemolytic Uremic Syndrome (aHUS)?
aHUS is a rare condition that affects your blood and kidneys. It causes tiny blood clots to form in small blood vessels, especially in the kidneys. This can lead to:
– Hemolytic anemia: Your red blood cells break down too quickly, making you feel tired or weak.
– Thrombocytopenia Low platelet count, which can cause bruising or bleeding.
– Kidney problems: Damage that might make your kidneys work less well, sometimes leading to kidney failure if not treated.
Unlike typical HUS (often caused by infections like E. coli), aHUS is “atypical” because it’s usually linked to problems in your body’s complement system—a part of your immune system that fights infections but can go into overdrive and attack your own cells. In about 60% of cases, like yours, it’s tied to genetic changes. Triggers like infections, pregnancy, or certain medications can set it off.
Your Genetic Test Results
Your tests show a change (called a mutation or variant) in the CD46 gene, specifically c.286+1G>C. This is a common variant seen in people with aHUS—it’s been found in about 10% of cases overall. The CD46 gene makes a protein called Membrane Cofactor Protein (MCP), which acts like a “brake” on the complement system to prevent it from damaging your own blood vessels and kidneys.
This particular change is at a “splice site,” which means it messes up how the gene’s instructions are put together. As a result, your body might make less of the MCP protein or a faulty version, leading to overactive complement and the symptoms of aHUS.It’s usually found in one copy of the gene (heterozygous), which is enough to increase risk, but not everyone with this variant gets aHUS—only about 28% do in studied families. This is called “incomplete penetrance,” meaning other factors (like a viral infection) are often needed to trigger it.
How Does This Affect You and Your Family?
aHUS with CD46 variants like yours is inherited in an autosomal dominant pattern. That means:
– You have two copies of every gene—one from each parent.
– If you inherited this variant from one parent, there’s a 50% chance you could pass it to each child.
– But because of incomplete penetrance, not everyone who inherits it will develop aHUS. Family members without symptoms might still carry it.
We recommend genetic testing for close relatives (parents, siblings, children) if they’re interested, especially if planning a family or if they have any kidney or blood issues. This can help with early monitoring. There’s no increased risk for more severe disease if both copies are affected—that’s rare for CD46.
Your Prognosis (What to Expect Long-Term)
The good news is that aHUS linked to CD46 variants generally has a better outlook than those tied to other genes (like CFH or CFI). Here is a summary:
– Short-term: Many people recover well from the first episode with treatment. The risk of death or severe kidney failure (end-stage renal disease, or ESRD) in the first year is low—around 0-6%
– Long-term: About 30-40% of people may eventually need dialysis or a kidney transplant, but up to 60-70% keep good kidney function over time. Relapses can happen (in about half of cases), often triggered by infections or stress, but they’re usually manageable.
– Kidney transplant: If needed, outcomes are strong—recurrence risk is low (less than 20%) because the new kidney produces normal MCP protein.This is better than for other genetic types, where recurrence can be 80%.
Overall, with modern treatments, most people live full lives. Factors like early diagnosis, avoiding triggers, and ongoing care improve your chances. Historically, prognosis was poorer, but that’s changed a lot in recent years.
Treatment Options
Treatment focuses on controlling the complement overactivity and supporting your kidneys:
– Medications: Eculizumab (Soliris) or ravulizumab (Ultomiris) are complement blockers that have transformed aHUS care—they stop attacks and protect kidneys.Many start on these lifelong, but some can taper off.
– Plasma therapy: In the past, this was common (exchanging blood plasma to replace missing proteins), but it’s less used now with complement blockers.
– Supportive care: Blood pressure control, dialysis if kidneys struggle temporarily, and avoiding triggers like certain drugs or infections.
– Monitoring: Regular blood tests, kidney function checks, and possibly complement levels.
Your doctor will tailor this based on your symptoms and tests.
Recommendations and Next Steps
– Follow up with your nephrologist (kidney specialist) and genetic counselor for ongoing monitoring.
– Consider family screening—talk to a genetic counsellor about risks and benefits.
– Lifestyle tips: Stay hydrated, get vaccinations (to prevent infections), and report any signs like fatigue, swelling, or dark urine early.
– Resources: Connect with patient groups like the aHUS Alliance for support.
If you have questions or need clarification, please reach out. We’re here to help you understand and manage this.
Best regards,
Your Genetic Counsellor or AI Assistant, based on current evidence
