New Info on A149P

[tummyache]

I was looking at something else and made a discovery on SNPedia this afternoon.[https://www.snpedia.com/index.php/Rs1800546] The site was just updated 28 May 2016, 2 days ago. There's been some changes made to information on rs1800546 [A149P]. Please look at the site and tell me what you think, as I am so confused now. I am CC on rs1800546 -- if I read this right, NOW it means this might be considered pathogenic for HFI??? That got me into digging more into the raw data on 23andMe and I discovered also i5012665 II (a double insertion) which I think may be significant too, even though it was never mentioned originally to me on 23andMe.  Interesting!

[colormist]

I don't really understand the article completely, so I can't comment without sounding like a dolt, however, did 23&Me tell you they would update your record as new information came available? Can you contact them and inquire about the results?

[bananafish]

Hi Tummyache,

You don't have to worry about this. First of all, the warning on SNPedia about orientation was from August 2015, so it's not new. The page was modified on 5/28/2016, but it wasn't modified to add that warning. They probably just had a small edit or something like that.

I think you are worried that 23andMe got it backwards and told you that you don't have the A149P mutation when you actually do. This is not the case. The way 23andMe analyzes and reports on rs1800546, CC is effectively the non-mutant genotype, regardless of what you see on SNPedia. So, on 23andMe, you should be concerned if you have GG, but not if you have CC.

SNPedia's warning arises from the fact that DNA is double stranded and there can be confusion between the sense strand and antisense strand when reporting on and analyzing genes. It is a real trap that even researchers have fallen into, but it is not a problem you have to worry about with regard to rs1800546 on 23andMe. Just going by logic, if 23andMe had it backwards, they would be reporting that 99% of the population has HFI, but that is not the case.

And you don't have to worry about the double insertion at i5012665. This is just a result of the way 23andMe analyzes and reports on this particular SNP. For this particular SNP, the mutant genotype is a deletion. So "insertion" in this case means "normal." I was confused by this at first too because, usually, "insertion" means "mutation." But, in reality, it all depends on the way the SNP probes are designed and reported.

Also, the two SNPs that you bring up, rs1800546 and i5012665, are linked to two of the four most common mutations associated with HFI - A149P and delta4E4. 23andMe looks at both of these for its "Inherited Conditions" analysis to tell you whether or not you have HFI. So if their "Inherited Conditions" analysis tells you that you do not have HFI, then you do not have the mutant genotype for either of these SNPs.

[tummyache]

Ir was really a surprise to see these 2 new alleles reported, because 2 years ago they were not included in the raw data report that I down loaded. Now, I also see other heterozygous ALDOB rs#'s too. I know 23andMe is currently revamping, updating data and their website will soon have a new look. They have not changed the health reporting info or are likely to do so until the FDA clears them with a go ahead. I have emailed to ask questions and they are not ready to be helpful in that way yet. So, it was really a surprise to find more info on my raw data. Meanwhile, my detective work has continued to try and figure out my particular difficulties with carbohydrates. In the 1970's they were so sure I had HFI and for years we have thought so. I continue still to have ferritin levels in the 500+ range [hemotologist says it is an "acute phase reactant" due to inflammation that no one can figure out the origin of to this date]-- new literature I have seen recently has led me to believe that this is one of the signs of mild liver inflammation in HFI. To cover bases, we did an upper endo + enzyme biopsies for Congenital Sucrase-Isomaltase Deficiency recently. I'm low, boarderline. But, still fructose is part of the problem and unfortunately the enzyme tests did not cover fructase. By the way, I have been having problems since the 2nd week of life as a baby. I have a very limited HFI/CSID diet by default.

[bananafish]

I really hope you can figure out what you have. It's so hard not to know, and I know that doctors are busy and every day they see examples of very obvious traumatic injuries, so I think, by comparison, they tend to discount chronic conditions and underestimate how hard it is to live with them.

I saw that there is a company called MNG Labs that does exome sequencing on 75 genes relating to carbohydrate metabolism. Here is a list of the genes they look at: www.genetests.org/tests/details.php?id=206446

The test is expensive (almost $2,000), but their price lists have CPT codes, so I'm assuming that means that it can be submitted to insurance. Whether the insurance will cover it is another matter, and might depend on the diagnostic code provided by your doctor.

Here is the price list:
mnglabs.com/fullpanel/uploads/files/mng_complete%20test%20list%20with%20prices,%20tat,%20and%20cpt%20codes%20(test%20code)_201508testlist01.pdf.

And here is the test requisition form that would be submitted by your doctor:
mnglabs.com/fullpanel/uploads/files/mng-ngs-testreq-201604ngs.pdf

This could be worthwhile for you since it does full exome sequencing and not just SNP analysis, so it would be more likely to catch an uncommon mutation.

[colormist]

I have noticed them appearing with citric acid as well--either that or something in my preference for vinegary foods. B5 isn't one of my glaringly low vitamins (like C, K, and E) but it's still floating at around 50% of my daily requirement. I have noticed I haven't had them recently--which just so happened to coincide with me taking my multivitamin regularly. I had considered that the ulcers were from a low vitamin intake, but I was more or less targeting C as a culprit.

I'll pay closer attention to the ulcers in the future and see if they start popping up again when I forget to take/run out of my multivitamins.

[bananafish]

Oh you get them too? Interesting... I wonder if low B5 is a common consequence of the low-fructose diet. And I know that all B Vitamins are important for carbohydrate metabolism, and B5 is specifically involved in energy metabolism, so maybe it gets used up quickly in the low-ATP crisis brought on by fructose.

I remember seeing on here that ukbill can't tolerate canola oil. When I was reading about citric acid, I saw that it is often used in processing canola oil. Makes me wonder...