HFI / FBPase / DFI?

[Mari]

Hello everyone!

I have been reading my way through this forum for weeks and finally found the courage to make an account, because I really need some help and advice and I'm hoping that you might be able to point me in the right direction. My story:

I am 31 and have been suffering from various health issues all my life, but no doctor has ever been able to explain what is wrong with me. I have been diagnosed with Hashimoto's Disease (hypothyroidism) and endometriosis, but even after treating these issues, I am still struggling with severe fatigue, crazy weight fluctuations (currently overweight) and bouts of hypoglycemia. The endocrinologist my GP referred me to thought I was a waste of his time, so my GP suggested getting a blood glucose meter and keeping a food diary to see if I have low blood sugar either after fasting or after meals. The answer is: both. My blood sugar drops below 3.5 nmol/l after 6 hours of fasting during the day, but I'm fine overnight as long as I eat lots of carbs for dinner. I also get low blood sugar after meals sometimes, and it took me a while and a mango smoothie to figure it out, but I seem to be reacting to fructose. My blood sugar rises after low-fructose meals or meals that have a lot of complex carbs in addition to fructose, but drops very quickly when I eat a meal high in fructose (I ran a little self-test with a bowl of fruit + 1 tbsp of sweetener with various sugar alcohols - it wasn't pleasant).

So I started googling and found you guys. After reading through pretty much the whole forum, I am still not sure if HFI/DFI/FBPase deficiency is a possibility, or if there is something else going on. What speaks against HFI is that I do not have an aversion to sweets and fruit - I just don't crave them very much and am satisfied with very small amounts. According to my mother, I had a lot of trouble with most formulas after she stopped breastfeeding me, until she finally found one I could tolerate. Since my mother also happens to be one of those 70s hippie tree huggers and my grandparents had a farm, we didn't have any processed foods in our house, were only allowed sugar on Sundays and only had juice and soft drinks on special occasions. And since I don't crave a lot of sweet foods, it may be possible that I have escaped large doses fructose for most of my life. It's hard to tell if I have digestive issues after eating fructose now, because I'm on antibiotics at least 4 times a year and take naproxen for endometriosis pain, so my digestive system is so messed up I get sick and bloated no matter what I eat. But I am definitely not lactose intolerant and not celiac (both have been tested). 

I realise that HFI and FBPase deficiency are very rare diseases and it is even rarer to be diagnosed as an adult. So before I run to my GP and he falls off his chair laughing or sends me straight to a shrink, I would like to hear your opinion and advice. Many many thanks in advance!

[colormist]

FIRST: Welcome to the board! I know it can be intimidating, but lots of people use this forum as a way to find their diagnosis (either HFI, FM/DFI, FBPase, etc) so we're happy to help any way that we can.

And high-five for fellow Endo! I feel your pain--nearly literally. I ended up getting a Implanon implant and haven't had a period in over seven months. Seriously the best decision I have ever made. I still occasionally bloat up like a balloon, but that's much more tolerable than the pain.

A couple other things:
1. I have diagnosed HFI.
2. My friends and family also thought I had some psychological issues because eating sweets made me sick, but pixy stix did not.
3. I went outside and ate wild cherries off my wild cherry tree this week. I probably should not have done this, but sometimes fruit finds a way into my mouth and it can't be helped.
4. Up until I got my formal diagnosis in my mid-20's, I ate all manner of things I shouldn't: strawberries, black raspberries, apple, carrots, cucumber, celery, tomatoes, ice cream, the bottoms of muffins, a portion of an oatmeal cookie, chocolates, donuts etc.
5. I didn't even notice that things were making me sick until I removed them from my diet.
6. My parents were not hippies, but largely Irish so our diet was mainly meat and potatoes. I hated summertime because then the really sweet foods were added (watermelon, cakes, ice cream, baked beans) into the mix.
7. There are a few people on the board here with confirmed HFI that enjoy sweets. Things that would make my jaw lock up in protest from mere association, they really quite enjoy without any adverse effects (as the sweetener is not fructose-based).

A couple questions for you:
1. Have you tried an elimination diet? This is what really helps you pin down the foods that are making you feel icky.
2. Do you get nauseated after you eat certain foods or after you haven't ate in a long while?

Based on what you've written here, and my 'totally not a doctor' degree in armchair HFI medical diagnosis, I am leaning real heavy on you having HFI. My recommendation is for you to go to your doctor, tell them you suspect you have HFI, ask for the genetic screening for HFI (because you need this on your medical chart if you have it--too many IV and meds have added sweeteners). If your doctor can't do the screening, then ask for a referral to a geneticist or someone that can perform the test. Let them know you get hypoglycemic after eating fruits and sweets. If you don't mention the hypoglycemia, then they're not really going to see a medical reason for the test (and your insurance probably will not cover the cost of the test). Thankfully doctors take hypoglycemia as a serious medical condition.

It's not a test that gives quick results, so you'll probably have to wait a month or two.

Lots of us on the forum were diagnosed as adults with HFI. My geneticist actually told me that I probably didn't have HFI because I would have died as a baby--that's how little they expect parents to be able to navigate this condition unawares. Thankfully babies are pretty good at refusing foods that make them sick and a lot of parents are pretty good about not feeding their babies foods that make them vomit. Thus the babies become children that are picky eaters who then become adults who think they have some sort of psychosomatic reaction to sweets.

[Mari]

Thank you for the warm welcome! Now I'm a bit less worried about being a total nutcase

I'm sorry to hear you are suffering from endometriosis as well, but high-five fellow endo sister! My GP keeps bugging me to try the coil or an implant, but after horrible experiences with the Depo shot and various contraceptive pills I'm not convinced yet.

Jun 16, 2016 9:42:14 GMT -5 colormist said:

A couple questions for you:
1. Have you tried an elimination diet? This is what really helps you pin down the foods that are making you feel icky.
2. Do you get nauseated after you eat certain foods or after you haven't ate in a long while?

I have been cutting out fructose as much as I can since last Friday, so no sugar, no wholegrain products, no fruit and no veg other than spices and a handful of mushrooms or spinach a day. Since I cook everything from scratch (I even bake my own bread), I don't have to worry about any hidden sugar in processed foods. I'm still using stevia without any additives though and I have pure unflavoured dextrose in case I get low blood sugar. Or should I cut these out as well?

I don't know if reducing my fructose intake is helping yet, because I got food poisoning from some dodgy chicken on Monday, but on the upside my intestines definitely got a thorough clean up

Jun 16, 2016 9:42:14 GMT -5 colormist said:

My recommendation is for you to go to your doctor, tell them you suspect you have HFI, ask for the genetic screening for HFI (because you need this on your medical chart if you have it--too many IV and meds have added sweeteners). If your doctor can't do the screening, then ask for a referral to a geneticist or someone that can perform the test. Let them know you get hypoglycemic after eating fruits and sweets. If you don't mention the hypoglycemia, then they're not really going to see a medical reason for the test (and your insurance probably will not cover the cost of the test). Thankfully doctors take hypoglycemia as a serious medical condition.

I live in the UK, so luckily I don't have to worry about insurance cover thanks to our free NHS. However, our NHS is also overstretched, so it can take up to 18 weeks to see a specialist consultant and GPs tend to be very reluctant to refer you (they are being pressured to save money), so I'll need some serious evidence to convince my doctor to refer me to a geneticist. I'm hoping that the data on my glucose meter, my food diary and an elimination diet will be enough. Do you know if there are any active forum members from the UK who have been diagnosed recently and could recommend a specialist?

Thanks so much again for your kind reply, this really gave me hope that there is something going on and it's not just in my head, even if it doesn't turn out to be HFI.

[colormist]

Yes! There are a few members here from the UK. Hopefully someone will chime in. You're actually in a better situation being in the UK as there are WAY less added sugars to everyday foods there than the states. I would think it would be much easier to go a very long time in the UK without discovering a diagnosis. It's also much easier to find safe foods.

There is the 23&Me test that screens for a few HFI markers (not all of them). I'm not sure if they also function in the UK, though. www.23andme.com

If your dextrose isn't medical grade, it might be cross contaminated with other sugars. I'm also not certain on stevia and I haven't used myself as a medical guinea pig yet to test it out. Maybe cut them out for 3-7 days and then try adding them back in?

The number of times I've confused salmonella for fructose poisoning is too damned high! It's always the chicken, too.

Good luck talking to your GP. Please check back in and let us know how you're doing! And feel free to shoot us any questions you might have. The UK-peeps might be better with food-based questions.

[Mari]

Thanks so much again for your advice! I just came back from my GP who believes me that something is clearly wrong with my metabolism, but is a bit at a loss what to do, because she already referred me to an endocrinologist twice last year and they rejected the referral (yay NHS). She can't directly refer me to a geneticist, but my rheumatologist might be able to when I see her next - in October.

I'm considering paying for the 23andme test you mentioned, but as far as I can see they only test for the most common HFI mutations and don't test for FBpase deficiency at all? So I'm wondering if it's worth ₤125, which I can't really spare at the moment.

Diet wise, reducing fructose has definitely helped to prevent low blood sugar shortly after meals, but I got into major trouble with fasting hypoglycemia, because I can't eat wholegrains and many high fibre foods on a low fructose diet. So I'm not sure what to do, because constantly stuffing myself with white bread, pasta or potatoes when I'm already overweight is not ideal. I can't go on a high fat, high protein diet either, because my body doesn't seem to be able to switch to burning fat instead, because when I eat e.g. steak and salad, my blood sugar just continues to drop as if I haven't eaten anything at all. So at the moment I feel like being stuck between a rock and a hard place. I'd be very grateful for any tips and advice!

[colormist]

The whole low blood sugar thing is exactly what's not helping with my weightloss, either. I tried switching to smaller portion sizes and adding in a lot of low-impact exercise, but it doesn't seem to be helping me lose weight (but I'm not gaining weight now, either, which I guess is good).

I did do a no-carb diet, which worked right up until I had to have my gallbladder removed, but I really hate eating meat and fat. It's just so gross. I definitely had to eat on a regular basis there for a while to keep my blood sugar in check, but after a while I was able to go for a very long time without eating (which was good because I hated eating). I didn't eat any veggies on this diet, so I had less problems with hypoglycemia than usual for me.

Yes, the 23&Me test only checks for HFI, only the most common genes, and doesn't test for FBpase at all. That's one of it's huge drawbacks, but it is helpful for people who are running out of options and can't get a doctor to cooperate (or can't afford to go to the doctor for the test).

[christopher]

Welcome Mari! Are you from the UK, or are your parents Scandinavian?

I second colormist´s suggestions to try keeping track of your all your meals with a food diary, as well as continuing using the glucose meter.

In addition to that I would suggest that you get yourself some of those "ketostix" that you pee on to reveal the presence of ketones in your urine. Ketones are a product the body (liver in fact) makes from fat, for the body to use as an easily available source of energy for the body to use under special circumstances. Glucose normally takes care of this role mostly on its own, but even healthy people might see traces of ketones in their morning urine from time to time, typically when they in addition to fasting during sleep did not eat for quite a while before going to bed, meaning they had fasted for quite some time in total. This is normal and nothing to fear. Ketones are also made by the liver when following a "ketogenic diet", which is always a very low carb (usually less than 20g carbs/day for most people, but some can go higher, i.e. athletes) quite low protein, but high in fats. This is also benign.

The body may also create ketones in times of metabolic distress, which sometimes happens to people suffering from type 1 diabetes. In their case the metabolic distress is called diabetic ketoacidosis, which I believe is caused by a lack of insulin, which role is to transport glucose from the blood into the cells, where it can be used as energy. Having insufficient insulin no glucose is transported and the cells are essentially starved, causing the liver to create huge amounts of ketones that are not as dependent on insulin for transport into the cells. If you do not have type 1 diabetes, this will not happen to you.

Ketones might also be produced during hypoglycemic episodes, as blood glucose levels are insufficient on their own, and I would suggest you experiment with measuring your levels at different times during the day but especially after you have felt "hypo".

If you happen to know someone who has access to one of those lactate meters that sports coaches, especially track and swimming coaches, use to measure lactate levels of their athletes during exercise, I would also suggest doing a few tests with that. The reason being that a few different disorders, including FBPase deficiency, may cause lactate levels to rise to abnormal levels from simply eating noxious sugars. I suspect having FBPase def. myself, and have performed a few such tests that revealed just such an abnormal response (in my case the response was to sorbitol, which is converted in the liver to fructose). You can search for "lactate" on the forums to find my write-up of my somewhat crude self-experiment.

What other reactions do you have from ingesting fructose or other noxious sugars? Do you get liver pain? Have you ever felt your any of your leg muscles tightening up, as if you had just ran a 1k all out, from just walking around after a meal?

[christopher]

I think it strange that you get hypo as soon as 4-6 hours after meals during the day, but seemingly do not have any major issues with your over night fasts. May I ask if you would post your blood sugar recordings, especially from your little "tests", postprandial readings and fasted morning readings? Also, do you have any sleep issues?

It is primarily gluconeogenesis (in which the liver creates glucose from non-glucose substrates such as lactate, amino acids, fructose, glycerol...) that is negatively affected in FBPase deficiency, while glycolysis (the liver using stored glycogen to release glucose into the bloodstream) as is normally mostly unaffected, I believe it is unlikely to be what you have, as glycolysis should be able to keep blood glucose in the normal range for up to 12-18 hours. Though, glycolysis may also suffer if the amount of ingested noxious sugars is sufficiently large, but that would normally require quite a large amount of fructose in order to happen, i.e. up 1-2g/kg bodyweight, if I am not mistaken.

Have you considered GSD1, as it impairs both gluconeogenesis and glycolysis? en.wikipedia.org/wiki/Glycogen_storage_disease_type_I

[Mari]

Dear both,

thank you so much for your detailed replies and sorry for not replying earlier, I have been knocked out with a nasty case of nephritis for three weeks. Since this isn't the first time my kidneys have become inflamed without any trace of infection and I'm already seeing a rheumatologist who suspects an autoimmune disease due to my family history and symptoms, my GP has referred me to a urologist who will hopefully be able to find the cause. My urine has been tested 6 times this year, so I assume they would have found lactate or ketones if there were any? The only thing they did find were small amounts of blood. I had a look at all blood tests done this year and the only abnormalities were slightly raised creatinine (kidneys), ALT (liver), creatine kinase (muscle damage) and lactate dehydrogenase - which is probably not what you meant by lactate (lactic acid), Christopher?

My GP regularly checks me for Diabetes Type I and Addison's Disease (which can cause hypoglycemia), because both run in my family along with Hashimoto's Disease and rheumatoid arthritis, but so far I've been lucky with "just" Hashimoto's Disease. Let's hope it stays that way, I really really do not want an autoimmune disease like Lupus, which is now a possibility due to my kidney issues, joint pain and skin rashes.

What other reactions do you have from ingesting fructose or other noxious sugars? Do you get liver pain? Have you ever felt your any of your leg muscles tightening up, as if you had just ran a 1k all out, from just walking around after a meal?

I don't seem to have any digestive issues other than getting bloated after eating large amounts of fructose (e.g. smoothie) and I don't get any leg cramps. For the past two months, I've been having random stabbing pains just below my ribs on the right side, which could be my liver, but my GP thinks it could also be my gall bladder or the kidney pain radiating to the front, which the urologist will hopefully be able to figure out. It doesn't seem to be related to food however and can occur at any time, even waking me up in the middle of the night.

I think it strange that you get hypo as soon as 4-6 hours after meals during the day, but seemingly do not have any major issues with your over night fasts. May I ask if you would post your blood sugar recordings, especially from your little "tests", postprandial readings and fasted morning readings?

The fastest drop I have recorded was from 5.1 nmol/l to 3.6 nmol/l within 20 minutes of eating 150 g of strawberries with 2 teaspoons of sweetener. I am fine overnight as long as I eat lots of carbohydrates, preferably wholegrains, for dinner. My fasting blood sugar in the morning is usually between 4.0 and 4.5 nmol/l. Since I started a low fructose diet, I have been having issues overnight again, because white carbs don't last very long. Last Monday, I had salmon with rice and spinach for dinner at 7 pm and woke up around 2 am with a splitting headache, fluttering heart and a blood sugar reading of 2.6 nmol/l. Yikes. So I've started eating wholegrains and vegetables high in fibre again, but am still staying away from fruit and sugar, because I did notice a difference and didn't feel like I had to lie down after meals anymore since starting this diet.

Also, do you have any sleep issues?

Yes, although this is most likely due to kidney pain and having to go to the bathroom 4-5 times a night

Have you considered GSD1, as it impairs both gluconeogenesis and glycolysis? en.wikipedia.org/wiki/Glycogen_storage_disease_type_I

Thanks for the suggestion! That sounds quite serious - wouldn't I be dead already in that case?

Are you from the UK, or are your parents Scandinavian?

Close - I'm German, but studied in the UK and am now working here. But who knows for how much longer after BREXIT

[jenn123]

In response to your question of wouldn't you have already passed with a GSD.
Prior to my child's diagnosis of HFI, she had a liver biopsy for GSD typeVI (hers disease). This is one of the milder forms of GSD, so not as tragic other types.
Google it and see if sounds familiar to you.
Hope you get answers soon 😊

[Mari]

Jul 12, 2016 13:23:26 GMT -5 jenn123 said:

In response to your question of wouldn't you have already passed with a GSD.
Prior to my child's diagnosis of HFI, she had a liver biopsy for GSD typeVI (hers disease). This is one of the milder forms of GSD, so not as tragic other types.
Google it and see if sounds familiar to you.
Hope you get answers soon 😊

Thank you   I will definitely mention it when I see my GP next

[jenn123]

Good luck - hoping for the best.

[christopher]

Jul 12, 2016 12:47:08 GMT -5 Mari said:

Dear both,

thank you so much for your detailed replies and sorry for not replying earlier, I have been knocked out with a nasty case of nephritis for three weeks. Since this isn't the first time my kidneys have become inflamed without any trace of infection and I'm already seeing a rheumatologist who suspects an autoimmune disease due to my family history and symptoms, my GP has referred me to a urologist who will hopefully be able to find the cause. My urine has been tested 6 times this year, so I assume they would have found lactate or ketones if there were any? The only thing they did find were small amounts of blood. I had a look at all blood tests done this year and the only abnormalities were slightly raised creatinine (kidneys), ALT (liver), creatine kinase (muscle damage) and lactate dehydrogenase - which is probably not what you meant by lactate (lactic acid), Christopher?

My GP regularly checks me for Diabetes Type I and Addison's Disease (which can cause hypoglycemia), because both run in my family along with Hashimoto's Disease and rheumatoid arthritis, but so far I've been lucky with "just" Hashimoto's Disease. Let's hope it stays that way, I really really do not want an autoimmune disease like Lupus, which is now a possibility due to my kidney issues, joint pain and skin rashes.


The urine tests would have to be taken during or immediately after a metabolic decompensation for lactate or ketones to appear in it. So no. 

As for the slightly elevated lactate dehydrogenase, no, that is not the same as lactate/lactic acid. It is slightly interesting non the less, as lactate dehydrogenase is the enzyme responsible for conversion of lactate to pyruvic acid, and the other way again. In my non-professional opinion having a raised blood level of this enzyme would indicate that your body needs to rid itself of more lactate than what is considered normal. That would indeed be the case if you were to have Fructose 1,6 diphosphate deficiency, as ingested noxious sugars in that case will be converted to lactate and released into the bloodstream. 
 

I think it strange that you get hypo as soon as 4-6 hours after meals during the day, but seemingly do not have any major issues with your over night fasts. May I ask if you would post your blood sugar recordings, especially from your little "tests", postprandial readings and fasted morning readings?

The fastest drop I have recorded was from 5.1 nmol/l to 3.6 nmol/l within 20 minutes of eating 150 g of strawberries with 2 teaspoons of sweetener. I am fine overnight as long as I eat lots of carbohydrates, preferably wholegrains, for dinner. My fasting blood sugar in the morning is usually between 4.0 and 4.5 nmol/l. Since I started a low fructose diet, I have been having issues overnight again, because white carbs don't last very long. Last Monday, I had salmon with rice and spinach for dinner at 7 pm and woke up around 2 am with a splitting headache, fluttering heart and a blood sugar reading of 2.6 nmol/l. Yikes. So I've started eating wholegrains and vegetables high in fibre again, but am still staying away from fruit and sugar, because I did notice a difference and didn't feel like I had to lie down after meals anymore since starting this diet.

Not to jump the gun here, but if you were to have FBPase deficiency, ingesting noxious sugars might not be the only cause of your hypos. Eating too much protein or fat can cause a similar response, as high levels of glycerol (the backbone from fatty acids) and a lot of amino acids (from protein) stimulate gluconeogenesis, in the same way as noxious sugars does to cause hypos. FBPase def. is an rather an inborn error of gluconeogenesis than it is an inborn error of fructose metabolism - like HFI is. The point at which fructose or noxious substrates cause our respective metabolisms to break down is entirely different. 

I would suggest you try to not only eliminate noxious sugars, but also limit how much protein and fat you eat, to 10% and 20-25% of your daily energy requirements, respectively, as suggested in the following paper: eknygos.lsmuni.lt/springer/223/II%20Part/135-142.pdf

Please let us know how it goes. 

PS. Please also check out my new post on depressive symptoms in connection with HFI/FBPase, in the adult section. 

[Mari]

Dear everyone,

thank you so much for your replies and sorry for disappearing again, I was running from test to test and seeing various specialists. The good news is: I know what I have, it's not a metabolic disorder, it's Ehlers Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS) and Gastroparesis, which in combination caused the symptoms I was experiencing. I'm going to explain it in detail below, in case anybody with symptoms of EDS, POTS and Gastroparesis will be scrolling through this forum in the future, but if you're not interested, feel free to skip it and just let me thank you for your support and encouragement in the past months 

EDS is a connective tissue disorder caused by a genetic mutation that results in faulty collagen. It makes your tissues more stretchy, but also more fragile, and can affect all organs (weak muscles & ligaments, skin that bruises easily and heals slowly, heart problems due to overly stretchy blood vessels, digestive issues and many more).

In POTS, which often occurs together with EDS, your heart and blood vessels struggle against gravity, causing your blood to pool in your legs and resulting in symptoms very similar to hypoglycemia (fast heart beat, dizziness & fainting, sweating, nausea). And guess what? Sugar makes it worse.

Now here comes the really interesting bit: Gastroparesis, or stomach paralysis, which means your stomach digests food very slowly or in severe cases not at all. When your stomach empties too slowly and struggles to digest food properly, this often results in nutrient deficiencies and unpredictable blood sugar fluctuations. I had a barium swallow test (X-Ray while drinking a radioactive milkshake), was instructed to fast for 12 hours, fasted for 16, because I felt full, and my dinner from the day before was still visible on the screen. No wonder I've had problems with fasting blood sugar. A lot of people with gastroparesis also report reactive hypoglycemia after meals high in refined sugars, but this is not very well researched yet. However, the interesting thing is that the diet prescribed for Gastroparesis is very similar to the HFI diet: avoid fruit, vegetables and wholegrains (plant fibre is too hard to digest) and stuff yourself with white carbs, meat and dairy. And since my POTS also gets worse with larger doses of sugar (including fruit juices etc.), of course I felt better on a low fructose diet.

Phew, what a roller coaster, I'm still a bit in shock after this diagnosis, but at least now I know what is going on. Thanks so much again for your help and I hope you don't mind me hanging around for a bit in this forum to look for low-fibre low-sugar recipes 

[christopher]

Great to hear that you´ve finally gotten some answers!

[rysmom14]

Glad to hear you have answers! it's crazy how there are so many overlapping symptoms and that even the low sugar diet is helpful for you too.