“What the heck hit me to cause that and why” are not an unreasonable question for aHUS patients to ask.
Collectively the genetic and triggering factors that cause aHUS are considerable and complex. It is no wonder that this agenda topic emerged.
Are the predisposing genetic and triggering factors of aHUS fully catalogued and understood and will it help to know how variable are the risks of these between individuals?
The research agenda expert answered:
“While there has been significant progress in understanding the genetic and triggering factors of atypical hemolytic uremic syndrome (aHUS), it’s important to note that aHUS remains a complex and multifactorial condition. The genetic factors associated with aHUS are not fully understood for every individual, and there can be genetic and non-genetic triggers that contribute to the development of the condition.
Some key points regarding aHUS genetics and triggers:
- Genetic Factors: Variants in genes related to the complement system, such as CFH, CFI, CFB, and others, have been identified as predisposing genetic factors for aHUS. However, not all individuals with aHUS have known genetic mutations.
- Variable Risk: The risk of developing aHUS can vary between individuals, even among those with known and the same genetic mutations e.g. in families. Environmental factors, infections, and other non-genetic triggers can influence the onset and severity of the disease.
- Complex Interactions: There is a complex interplay between genetic susceptibility and environmental triggers in the development of aHUS. The specific triggers and mechanisms can vary from person to person.
- Ongoing Research: Research in the field of aHUS genetics and triggers is ongoing, and scientists continue to uncover new insights into the condition.
Understanding the individual variability in aHUS risk and triggers is a key area of research. Knowing the specific genetic and non-genetic factors that contribute to a person’s aHUS can help tailor treatment and management strategies to their unique needs. Healthcare providers may conduct genetic testing and assessments to better understand the factors influencing a patient’s aHUS and provide personalized care.
There are databases that compile genetic variants that cause complement system disorders, including atypical Hemolytic Uremic Syndrome (aHUS). One such database is the Human Gene Mutation Database (HGMD), which provides information on disease-related human gene mutations. Another resource is ClinVar, a freely accessible database maintained by the National Center for Biotechnology Information (NCBI), which includes information about genetic variations and their relationships to diseases.
There isn’t a single, exhaustive list of conditions that trigger atypical Hemolytic Uremic Syndrome (aHUS) because the development of aHUS is complex, and various factors can contribute.
It’s important to note that databases and resources are continually updated, and new ones may emerge. I recommend checking the latest literature, genetic databases, or consulting with geneticists and healthcare professionals for the most current information regarding complement system genetic variants and aHUS.
Other than the University College of London’s Complement Mutations Database attempt at a comprehensive record of all complement variants , disease causing or not, Global Action was not aware of other databases especially HGMD or ClinVal. A quick check of the latter produced a list of 672 Complement Factor H variants some of which were aHUS causing. So those two databases need to be looked at in more depth sometime!
However, so as far as Global Action is concerned the simple answer to the first of the questions about genetic factors is “yes, maybe”. For the triggering conditions list “no” and does knowing the variability help “yes”.
The key problems are the awareness and the sustainability of maintaining such database and lists. Databases are rarely complete to begin with and become out of date over time unless there is an inclusive and robust update system feeding into them.”
Maybe one day when the technology becomes available there will be a way to maintain complete records of each cause of aHUS , but until then, they will remain mostly not fully catalogued.
Article No. 614
It is known that certain rare genetic variants, mutations, or markers, in components of the Complement System make some people susceptible to aHUS. it is less known that there are…