The most common enzyme deficiency and why it took me so long to figure things out
This is a different kind of article than the ones I usually write, but I thought it was important to write it. It will have some technical details at the end about a relevant side project, but it is definitely not technical in content. I wrote this in hope that it will be helpful to someone, because my experience could have been avoided with a little bit of more information.
What is Glucose-6-phosphate dehydrogenase (G6PD) Deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. Following a specific trigger, symptoms such as yellowish skin, dark urine, shortness of breath, and feeling tired may develop. Complications can include anemia and newborn jaundice. Some people never have symptoms.
Taken right from wikipedia.
It passes from mother to son and from father to daughter and it seems to affect males the most. You might be partially or fully deficient. This might play a role in how the triggers affect you, but it is really not that clear to me. You can read more on inheritance in the excellent article of the G6PD Deficiency Foundation here.
I will not go into too much medical details, but I’ll put links in the last section, in case anyone is interested to dig deeper.
How I got into trouble
I’ve always known, since I was a kid, that I had something called G6PD deficiency (G6PDD), an enzyme deficiency that means you should not ingest certain food and medication. My mum has it (and almost died from it when she was a kid), and my dad must have had it also, since it passes from father to daughter and not from mother to daughter. However, he was never tested, so we’ll never know (my dad passed away on 2010).
“Ah, you’ve got the enzyme deficiency, that’s ok, just don’t eat fava beans and don’t take aspirin” and that was pretty much it.
But even though my mum always kept reminding me of the fact that I have this deficiency, I didn’t actually comprehend what it meant, not really. I mean, all doctors would, back then, tell you “Ah, you’ve got the enzyme deficiency, that’s ok, just don’t eat fava beans and don’t take aspirin” and that was pretty much it. For some, this is the case even now…
As I was growing up, I sort of tested the limits of this myself, with the quite fallible logic of: I tried blueberries, they didn’t do anything to me, I am ok, I can eat blueberries (even though there are certain kind of blueberries that are not safe, so perhaps I was just lucky). But I never knew exactly what the long term side-effects of having G6PDD and not adhering to the rules were.
Until about 3–4 years ago.
I’d been seeing an endocrinologist for quite a long time, because I had to monitor my thyroid function due to my family history. At this point, I was always very tired, my iron deficiency would not improve even though I’ve been taking supplements like for ever, I was getting sick all the time, my hair was thin, my face was pale and exercise was very difficult for me. And even though he had told me that I am hypothyroid, he didn’t suggest a treatment for this, but instead he went on prescribing me with a drug whose main substance is Metformin, with the goal to battle insulin resistance and be finally able lose some weight and feel better. (This has a point, I promise :) ). He was aware I was G6PDD. Metformin is a substance that G6PDD people should not ingest. I was not aware of this fact back then, so I agreed to try, because at that point I was really desperate to feel better.
I was on it for about a year, and even though it did terrible things to my health (to a point where I had to see many doctors for the problems it caused me), I kept on taking it, since the doctor’s approach was to ignore my complaints about how this had affected everything in my life and tell me to stick with it, that it’ll work and all we had to do was up the dosage.
Nothing good was happening though, and, after I ended up needing an iron transfusion — which the doctor prescribed — I got to a point where I could barely stand up, let alone function. I felt desperate, like, this cannot be it. Will I be like this my whole life? I now know that part of what I was going through back then was (low level) hemolysis, I’ll never find out exactly though because no relevant blood test were done to track this while I was taking this drug.
The slow recovery
I decided to take things into my own hands and stop Metformin. After a while I also cut down on gluten and refined sugar. I saw my health gradually improve, but the low energy persisted. My then boyfriend and now husband persuaded me to find another endocrinologist. And I cannot thank him enough for this! The new doctor was a lot different in her approach towards me and took a look at me as a whole. She saw the pale skin, the tiredness and everything and despite my “normal” blood tests, she clearly understood that I am hypothyroid. That changed everything. After the first month of the treatment I started feeling like a normal person again. It was a revelation, an “Aha” moment, like remembering how good it felt when you were a child and you had energy (which was also a rare thing for me but there were moments). We had to adjust the medication quite a few times — and we still are figuring it out— but everything feels a lot better now, plus my iron deficiency is also gone.
The — better late than never — realization
Even though I was on thyroid medication and my energy was better in general, there were days, or weeks that it was so very low, it was like I couldn’t drag my feed and there wasn’t enough oxygen for me. Now, the whole Metformin incident was not enough for me to put two and two together. After all, why not trust the specialist doctor, who should be aware of the patient’s needs and characteristics?
Triggers and Soy
That’s where a major trigger for me comes in. Soy. And more specifically, soy sauce. I had to eat the same food twice, have a hemolytic episode twice to fully grasp what was going on. (Yes yes, I know, not the fastest learner on this).
Noodles with soy sauce was what caused me to actually pay attention to what was happening to my body. After about half an hour of eating a delicious meal of noodles, my body started shutting down, to the point where I couldn’t keep my eyes open and I absolutely had to sleep. It took my body about a week to get back to normal again. The second time the connection was more obvious, I was more aware of the whole process, my breathing changed because the oxygen was not enough for me, my heart raced even though I was just sitting, my face became pale, I felt dizzy and my hands got shaky every time I attempted to use them. That’s when it clicked and I researched about the symptoms of hemolysis.
Hemolysis and Low Level Hemolysis
Hemolysis is, simply put, is when your red blood cells are broken down and destroyed at a rate that your body cannot keep up with replacing them. Some of the symptoms of hemolysis that are also common in other type of anemias:
- paleness of the skin
- weakness or inability to do physical activity
Other symptoms include:
- dark urine
- yellowing of the skin and the whites of the eyes (jaundice)
- heart murmur
- increased heart rate
- enlarged spleen
- enlarged liver
Low level hemolysis is basically when you are exposed to a trigger (either food or drug / substance) in a way that it is not enough for you to go to full blown hemolysis, e.g. you ate a few soy beans, but enough to put a strain on your body trying to keep up with the damage being done. You can read up more on this on https://g6pddeficiency.org, created by Dale Baker to spread awareness about this enzyme deficiency. There’s also an interesting video explaining how low level hemolysis works. I’ll be putting it in the links below.
How I deal with it
Looking back now, I realize I’ve had those kind of episodes a lot through out my adult life and I always attributed them to things like iron deficiency. It also seems that I now am more sensitive to the triggers — perhaps the accumulated damage has caught up with me, or I am just more aware because I understand the mechanism better — but I am also a lot more careful.
Being careful and reading all the labels trying to decipher the ingredients and remember if they are allowed to ingest or not or what is the limit on the dosage, can be quite exhausting. The list of triggers is big, e.g. drugs to avoid list, and most of them are not updated to include new drugs and new research results.
What I also do is to make sure to inform my doctors about this and at the same time double check the medication I am prescribed to avoid new Metformin incidents. This would also be my suggestion to you.
And as careful as I am, I still get these episodes once in a while. For example, during my pregnancy’s first trimester (I am currently in my third trimester, so this is the latest episode I had), I had awful nausea and heart-burn 24/7. The gynecologist prescribed me with antacids, typical over the counter antacids, that did a great job in easing my symptoms, but at some point I started getting symptoms that were not pregnancy related. Blood tests confirmed I was going through hemolysis. And that, we assumed, was because all (or almost all) antacids have menthol in them, which is on the avoid list. Again, it should be noted that I displayed the hemolytic symptoms because I was taking them so frequently and that had I taken only one tablet, I wouldn’t have such a horrible experience. This doesn’t mean of course that taking them less frequently is safe, it is just that the damage is not very visible.
An attempt to make the trigger checking easier
This process of checking the product labels got me thinking. In an attempt to make the trigger checking easier, I had the idea to leverage Deep Learning, and more specifically Google’s Vision API for OCR and create a simple web app where you can upload a photo of a product’s ingredients and quickly rule out the basic triggers. The results of course are not 100% accurate because of the many trigger naming variations and the different image qualities but the goal here is to be able to cross-reference the ingredients with the triggers’ list as easily as possible. If something bad doesn’t come up, that doesn’t mean that the product is safe. If it does though, then you can be sure that it is not safe for a G6PDD person.
This is still in an alpha phase of course and it is a side project. My long-term goal would be to be able to do this trigger detection real-time using your phone’s camera because for now it takes quite some time to round-trip and complete the check.
The initial attempt was done with an OCR library, pytesseract, but Google’s Vision API for OCR seems to have much better results. The front-end is written in Angular and the back-end is a simple Flask API.
Some screenshots on how this works:
The results are obviously far from perfect, as is the interface, but as I said this is in alpha state.
- Gather up as many lists of triggers as possible, with as many variations as possible, e.g. product name, substance name and so on.
- Preprocess that text in a way that it will be easier to match with what Google Vision API returns.
- Figure out a way to turn this into a real-time thing or at least speed things up.
- Add a feedback mechanism to gather training material and possibly be able to train a model on it to have better refined results.
- Deploy under g6pdd.info.
- Open source it.
Let me know if you think this could be useful and how it could be improved :)
This was a brief walk-through of my experience with G6PD deficiency. I am not an expert on this and it is definitely not the usual case for G6PD deficient people, some experience this worse, some never ever exhibit symptoms. There are many things that G6PD deficiency affects, for example the thyroid function due to reduced glutathione, the blood sugar regulation and so on, so I highly suggest you do your research and cross-reference your symptoms with what you come up with.
I hope someone will find this helpful in some way. I would love to know if you have any experience with this, how you deal with it and if you’ve found knowledgeable doctors that have helped you.
Edit: I removed the mushroom reference since the information I’ve found about it was inconclusive regarding to G6PDd.
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