I live!

I said that I would update my blog soon, but three months passed and I let the blog lie fallow. As spring has come, my website layout emerged from the snowy winter to grow new flowers.

Last semester, I ended up withdrawing from a difficult course due to poor health. Perhaps you were on tenterhooks all these months reading about the medical mystery that plagued me. Was it rheumatic fever? Was it cancer? Was it Castleman’s disease? Was it Munchausen’s symdrome, the favorite illness of people who make random stuff up?

It turns out that it was none of these things. By some completely random coincidence, the first genetic test that I took for periodic fever syndromes did not test for every variant that could potentially cause disease, just the main ones that cause almost all of the instances of disease, which is understandable. However, the second genetic test found a “variant of unknown significance” which was apparently, unfortunately, inherited in an autosomal dominant pattern since only one gene was affected. The gene that I had this mutation on is the MEFV gene, responsible for creating a protein called “pyrin”. Pyrin’s exact function is not fully understood,¹ but it seems to be associated with the inflammasome, which is why I would have systemic inflammation, high fevers, pain everywhere in my body, and crazy biomarkers that indicated that my body thought I had a massive, sepsis-level infection. The disease that occurs when you have mutant pyrin is called “Familial Mediterranean Fever”. Strangely, nobody else in my family has it, and I am not from the Mediterranean. This was a hypothesis that was tossed out early in the differential diagnosis process, but was discarded due to the first genetic test, which did not take into account the complex allele².

You may ask: “What is a complex allele?”

Here is my very basic explanation. Imagine that you have two chromosomes, and the genes look something like this, where “O” represents the normal gene and “X” represents the mutated allele. There are a couple of ways that you can have two mutations.

Scenario 1: Homozygous recessive

Most of the time, you might see something like this for someone with two mutations, which is the classic recessive inheritance (which you would normally think of when it comes to genetic diseases):

Chromosome A: [O O X O O]

Chromosome B: [O O X O O]

Scenario 2: Compound heterozygosity

And sometimes, someone might have something called “compound heterozygosity”, where each chromosome has a mutation in the gene, but they are different mutations:

Chromosome A: [O O X O O]

Chromosome B: [O O O O X]

Scenario 3: Complex allele

In a complex allele, two mutations happened on the same chromosome on the same gene. These two mutations might be benign on their own, but in tandem end up creating a mutant protein that loses function, has gain-of function, has a different function, etcetera.

Chromosome A: [O O X O X]

Chromosome B: [O O O O O]

So I have the third type, where there are two bad mutations that happen on the same chromosome. It’s very unlucky, because it seems like on their own, even if you had 2 copies of either one of them, you aren’t very likely to get sick. In fact, both of the individual variants are fairly common in the population. It’s only if you have both of them on the same gene at once that seems to be related to disease.

However, I was able to find lots of case reports and documentation for the variant that I had!³

I was so relieved to find out that I didn’t have lymphoma, but not so relieved to find out that I had a permanent, autosomal dominantly inheritable genetic condition. I also spent a lot of time freaking out about the fact that the biggest symptom of familial Mediterranean fever, other than having recurring high fevers, random attacks of severe pain in random parts of your body, and generally being attacked by illness out of nowhere, is that even when you don’t have attacks, due to the constant low-grade inflammatory process going on, your liver starts creating massive quantities of this protein called “serum amyloid A” which has a propensity to misfold and create plaques (sort of like with Alzheimer’s disease) except instead of accumulating in your brain and causing dementia, the protein accumulates in your kidneys and causes chronic irreversable renal failure.

However, after reading a little more about the mutation I have, it seems a little less associated with amyloidosis, so I feel a little more safe from dying at the age of 40 like most people with untreated FMF do. Now I just have to take a somewhat unpleasant medication twice a day (or perhaps more) for the rest of my life and never eating grapefruits or drinking tonic water ever again. But it’s a very cheap medication that’s available everywhere, so I guess it’s OK.

That was actually a very long digression about my Disease⁴, and the main point that I wanted to make at the beginning of my blog post was that, because I had withdrawn from a course due to illness last semester, I had gotten used to the relatively leisurely life of only taking 4 courses for credit (plus 2 that are mandatory but not for credit). This semester, I am taking 5 courses for credit (plus 2 that are mandatory but not for credit). It turns out that this is actually much more difficult!

After several months of nonstop homework assignments, the midterm season snuck up on me. I have been told that graduate school is the place where you are forced to come to terms with not getting 100% on your exams just by preparing well, and… well… Yeah.

The curve on the “Theory of Statistics” exam is 0-28 out of 75 will give you a C+. That’s how badly everyone did. And today I had another midterm in “Theory of Survival Analysis”⁵. It was one of those exams where there’s a single page with 5 questions on it and you get 2 hours to answer them. What I will say about it is that I was able to understand what every question was asking for, had a vague idea of how to proceed in the question, and showed a lot of work to get some sort of answer.

Hopefully the professor will take mercy on me and allow me to pass the class with the lowest passing grade. That’s all I’m really asking for, because I don’t want to retake the course!

Oh, my academic self-concept is in shambles… haha…

I have to laugh because otherwise I might cry. All that time spent studying to get completely obliterated by two exams in a row (the “Introduction to Machine Learning” exam, in contrast, was borderline pleasant in comparison).

Now that spring break is here, I’ll spend my leisure time on such pursuits as:

• Going to the doctor even more
• Updating my website
• Making a Vtuber model (maybe)
• Drinking hilarious quantities of sparkling water
• Adding the latest month’s Pikmin to my Pikmin page

I updated my normal blog layout to have Pikmin for the springtime, added (responsive) drop caps to my blog posts, and soon I’ll add some more people’s buttons to my greenhouse page!

During my hiatus, I ended up using status.cafe to microblog a little bit, and enjoyed clicking on random people’s profiles and reading their sites. I hope it isn’t too weird to do that. It’s just really fun to see what different people online are up to! And it’s always nice to leave a friendly comment on someone else’s guestbook.

Thanks to the follies of youth, I’m so used to the loner life and to the hostile Twitter/Tumblr⁶ world of people getting really mad about “interacting” with their “content” that I’m not sure if it’s weird to say hi like that. It’s not like my online presence even meets any of that “do not interact” criteria; I like to imagine that I’m a fairly decent and nice person,⁷ this page is completely SFW, and even if I do like a TV show that someone doesn’t like, I don’t really have the tendency to become a “that TV show” blogger. I used to say things like “I’ll never be too old for fandom!” but now that I’m nearly 29 years old, maybe something changed, and I did get too old for fandom. Or maybe the way that I participated in fandom was too juvenile and now I have to find a new way to engage in fannish activity. Maybe after all these years I’ll write a fanfiction? Haha.

Something fun I imagined for the future of this blog was the idea of implementing sidenotes, but I’m not sure if there’s enough screen space in my layout to do so. I’d hate to displace my little Pikmin… Well, if you ever want to do it, the link has a pretty exhaustive writeup of different ways to implement sidenotes!

I wonder what else the future of this blog might hold! It’s fun to create a “living document” like this. I’d like to add more and more stuff to it, but I also don’t want it to get too cluttered. Hm…