Compound heterozygous

[dzhura]

Dear members of the board and guests,

I'd like to share my story with you.

I am a mother of a 5-year old girl from Ukraine (Eastern Europe, former Soviet Union Republic). As a baby, my girl was normal, I breastfed her until 16 months. The only distinguished feature about her was that she refused to eat sweet food, fruits, juices and most vegetables. I stopped trying after she spit it up a few times. Her diet consisted of milk - she could drink milk all day and be fine, meat, eggs, not sweet cereals (out meal, buckwheat etc). She could eat some soup consisting of potatoes, cauliflower and other vegetables. By the age of 2 she was a chubby girl with a big belly.

Around 2 she started having problems sleeping at night and we took her to neurologist who did not find any problems and referred us to a gastroenterologist. She had her liver-function tests and ultrasound done the first time, and we found out she had problems there - she had diffusive changes of the liver (chronic process), her ALT/ACT were 3 times higher than normal. The doctor told us it's serious and we have to find out the reason. For the next year we tested her for Celiac disease, all possible worms including toxocars and echinoccocus, virus Hepatitis B and C, Epshtein-Barr's disease (not sure about spelling), pseudo tuberculosis etc. She kept refusing sweets and fruits/most vegetables but of course I did not watch the medicines. When she was almost 3, she got very sick and was placed at the hospital. It looked like very bad food poisoning, in fact she was almost in coma unable to eat/drink, she stayed in bed and got glucose and something else through medicine dropped all day. Her ALT and ACT were over 1000 (norm under 30). She had acute hepatitis of unknown character. It was a nightmare for my family - I had a second baby by that time, 2-months old boy and I was torn between a hospital and a baby. My daughter was tested again for Hep B,C, and all known hepatitis (E, Delta) - all negative. In about 3 weeks she got better and we took her home with strong recommendation to consult genetic doctor. Around that time I started researching on line and found an article about fructosemia (HFI) and all the pieces of the puzzle came together for me - right before my daughter became so sick, my mother was giving her cough syrup by force because she had a pretty bad cough. I was at the hospital with my baby son at the time - he had pneumonia.

Anyway, we went to see the genetic doctor and had lots of tests done to rule our glycogen disease (VI and IX type as the other types are more severe), Wilson's disease and autoimmune hepatitis. Her urine genetic test showed signs of fructose in urine. We had a genetic test done for most common mutations in gene ALDOB and the result was as following:
they found a common mutation A174D in heterozygous state. I was told if we do a complete screen of ALDOB, we'll find the second part as well. We did the second test and the result was as following: my daughter is a carrier - compound heterozygotous on 2 mutations - c.519C>G (p.Tyr173Term) /c.521C>A(p.Ala174Asp) in gene ALDOB and the diagnosis HEREDITARY FRUCTOSEMIA can be confirmed. The tests were done in Russia where they send them for confirmation to Germany. Our genetic doctor (who is considered to be the best in Ukraine) told us she has FHI, but 2 different mutations that weaken each other (not 2 copies of the same one) - I am a carrier of one mutation, my husband is a carrier of one mutation as well but not of the same kind.

I really hope my daughter has HFI and not something worse than that. Our biggest problem is not to watch the diet (she keeps the proper diet since she was 6 months old) but to watch the liver because in the future we may face fibrosis and liver transplant. We give her liver-protection medicine called Ursofalk. Besides, my daughter has bad constipation all the time. We give her live bacterias, flax cellulose and mineral water. In general she is doing OK. When she gets treats from birthday children in her kindergarten (sweets, juice, fruits) she brings them home to give to her younger brother.

Speaking of the younger brother, he is a healthy little boy who dies for candies and sweets. His liver is OK, he has no problems eating sweet and fruits. We don't see a point of testing him now because the test is kind of expensive - $1,000. he is either healthy or asymptomatic carrier.

I wonder if there are many people with HFI who have liver problems and constipation? We give our daughter a liver-protection medicine called Ursofalk once in 6 months.

I'd like to add that I found answers to the questions I was interested in on this forum - many thanks to people who posted links with valuable information! For example, my daughter can eat food that I thought was bad for her - potato chips (sweetners), hotdogs (soya), salty popcorn (corn). But they are safe for her! On the contrary, I thought the nuts are safe and she refuses to eat them. They are not safe!

[ukbill]

I would say from your very accurate and detailed description she is positively HFI!

You do not mention any reactions to eating sugars however, and I would expect her to go very limp and feel ill if she accidentally eats something sweet.

She must still be getting far too much sugar and fructose in her diet if she is still having liver problems.

It is very common for an HFI child to get used to eating foods that actually contain a lot of sugar.

This is sometimes because of hunger but more often because the sugar (or Fructose) is masked by a lot of Carbohydrates and fats.

Or even because its a contaminant in another "safe" sugar like Glucose / Dextrose.

A soup made with potatoes and cauliflower would cause me a lot of problems.. both these foods are very problematic because they contain far too much sugar.

Some varieties of Potato are close to safe but it depends on how they are cooked.

Putting them in a soup will not be good as all the fructose in the potato will be in the soup.

IF you need to make potato soup then chop the potatoes up small and soak them in water over night before changing the water and boiling them to just cooked, removing them from the cooking water and putting them into the soup.

Please do not use the cooking water form vegetables in any food for your daughter a lot of sugar form vegetables comes out int he cooking into the water.

Yes a lot of the taste has gone and almost all of the vitamins will have gone into the water as well but what is left is high quality starch which is really just long chain Glucose molecules.

Leave out the Cauliflower all together.. and cabbage also.

I think you like dumplings in the Ukraine.. a good meat broth with Dumplings will be great for her.

Potato Dumplings are OK as well or at least the ones I had in the Czech Republic were anyway

Constipation is normal also!

I have to take a none digestible plant fiber to help sort this problem out.

Its called Psyllium seed husks and you what the whole husks not the ground powder which is more digestible.

en.wikipedia.org/wiki/Psyllium_seed_husks

If you are unable to obtain them in the Ukraine let me know and I will sort out a method of getting you some sent over.

Keep smiling..

Your young son is going to LOVE his big sister bringing him sweets all the time

[dzhura]

My daughter very rarely has reaction to improper food - not nearly as often as described here. I don't know if it's because she always eats the right food or she is more fructose tolerant than most people with HFI. However, for the last year she was sick about 3-4 times with vomiting, stomach pain, bad dehydration and weakness afterwords that lasted for a few days. I think it's a reaction to fructose, not regular food poisoning because she never has diarrhea.

As far as potatoes, she does not eat them cooked but she sometimes asks for a raw one, I peel it for her, she can eat half of it and feel fine. She does not eat raw or cooked cabbage but she can eat a little bit of sauerkraut and pickles.

I will look for Psyllium seed husks in Ukraine. Can regular bran substitute it?
Ukbill, thank you for your kind offer to send it. I may ask you to do it later.

[tikitavi]

Re: constipation; casein in dairy products causes constipation for many people. That is why I take DPP-IV enzymes when I have dairy (I use it for opioid effects of gluten also). I do not suffer constipation as long as I take the DPP-IV enzymes every time I have dairy.

Another option is to try goat milk instead of cow milk products. Goat milk has a different type of casein which isn't as constipating for some people.

These articles describe all of this a little more:
www.livestrong.com/article/542333-what-causes-people-to-not-digest-gluten-casein-properly/
www.sharonhespe.com.au/blog/item/33-why-casein-a-protein-in-dairy-is-a-problem

I get my enzymes from iHerb.com and they do ship internationally. The name of the enzymes that I get is Digest Spectrum.

[dzhura]

What about bran extracted from flax seeds? Does it also contain sugar?

[dzhura]

ukbill,
Please look at the link - can I buy this Psyllium seed husk for my daughter? I have friends traveling from the USA soon, they can bring me this.

www.drugstore.com/gnc-natural-brand-psyllium-seed-husk-500mg-capsules/qxp138279?catid=16869&fromsrch=Psyllium%20seed%20husks

Thanks to everybody for your responses!

[dzhura]

Here is an article from Wikipedia about compound heterozygosity.
en.wikipedia.org/wiki/Compound_heterozygosity

Here is an article about gene studies. it says there that compound heterozygotes have HFI along with homozygores.

www.clinchem.org/content/44/5/1041.full

This may be an explanation to why some HFI people can eat more sugar than others?

[dzhura]

Here is an interesting article as well:

www.ncbi.nlm.nih.gov/pmc/articles/PMC1683824/?tool=pubmed

Dr. Tolan writes:
"Of 41 HFI patients in the present study,
29.3% were compound heterozygotes with an uncommon,
or unknown, allele. There appears to be a variety
of alleles for this disease, some more prominant than
others. It will be interesting to see whether the allele
frequencies in this population are mirrored in other
populations.
The molecular analysis in this disease is important,
as HFI heterozygotes have sufficient aldolase activity
and cannot be readily identified. Furthermore, diagnosis
of homozygotes is often difficult, requiring a fructoseloading
test and an enzyme assay from a liver biopsy
(Lameire et al. 1978). We report here a rapid method
for screening for known alleles (ASOs) and for identification
of new alleles that cause HFI. These methods will
enable a more rapid and less invasive method for diagnosis,
carrier detection, and possible neonatal screening
for this disease."

[ukbill]

Dzhura

Sorry for long delay in answering.

Try this instead. its cheaper and I feel that if the husks are ground then more of them might be digestible than if the husks are whole.

www.drugstore.com/search/search_results.asp?N=0&Ntx=mode%2bmatchallpartial&srchtree=1&Ntt=Psyllium+Husk+Whole+Vegetarian+-+1+lb&Ntk=All

I add it to my breakfast cereal (2 teaspoons full ) or make a milk shake of 1/2 fat milk and plain yogurt mixed and whisk in my 2 teaspoons full, leave for 10 min for the husks to jell up and whisk again before drinking.

[ukbill]

The reason we have to avoid bran is because all digestible fiber is broken down in the gut to produce sucrose! which causes us lots of gut pain and IBS type symptoms.

in my case I had lots of constipation because for one thing I had a very low fiber intake and I also had a diet which contained a lot of eggs which are really good for bunging you up.. particularly hard boiled which I used to take with me whenever I went out walking or playing with my mates as an HFI safe snack.

[dzhura]

Ukbill,
Thank you very much!
My friends will buy me Psyllium Husk Whole Vegetarian in the US.

[carolyn]

Hi all,
I haven't had much success on the constipation front with Psyllium husks, but maybe because I bought them in capsule form. What does seem to be OK for me is porridge made with oatbran. I daren't touch wheat bran. I hope I'm not doing myself any damage with the oatbran. I tend to stick with what I seem to be able to tolerate OK.

[ukbill]

The capsules contain finely ground husks. I suspect the fine texture and the fact that there are more edges to the fibre allows more to be digested, this is not what we want. the whole husks gel up and pass through the bowel intact if they get digested they will release sucrose into the gut which is NOT what we want.!

I have two or more heaped teaspoons full of whole husks in my breakfast cereal and it works fine.

I would imagine the number of capsules needed to equal that would be huge! even in ground form.

Keep smiling