Help understanding results from 23andme

[christopher]

Hi everyone, 

Not having found anything in terms of getting closer to a diagnosis by looking at my 23andme raw data before, I recently stumbled upon something that I find very interesting by running my raw data through Livewello.

I have found a single homozygous mutation in the AGL gene, in which the affected sNP seems - as per my limited understanding of genetics research - seems to be implicated in Glycogen storage disorder type III. 

The AGL gene provides instructions for making the glycogen deb ranching enzyme. GSD III is usually treated with a high protein diet - which seems to be giving me great results, by the way. Of course this seems too easy to be true. Could this really be it? Would someone more intimate with genetic research give me some feedback on this please? 

According to Livewello - and the template I installed - my "genotype for AGL rs3736296 is TT. Each chromosome from both of this person’s parents, carries the genetic variation which is determined by the presence of the variant allele: T"

and the sNP seems to be implicated in GSD III: 

www.researchgate.net/publication/278112644_Mutational_analysis_of_ten_Turkish_patients_with_glycogen_storage_disease_type_III_identification_of_four_novel_mutations

and 

proteomics.bio21.unimelb.edu.au/lovd/variants/0001328104#12565


Does this mean I have GSD type III? Any and all feedback will be greatly appreciated. 

[colormist]

Hi Christopher!
It sounds like you've got some pretty good clues as to what might be causing your health concerns. I'm not sure we have many geneticists here (if any at all). It might be helpful for you to schedule an appointment with a geneticist (or your doctor) to go over the results and get their opinion on your test data and suspicions.

If it is GSD III, then they probably have some ideas on how to treat the condition.

Good luck!

[tummyache]

Hi Christopher! You are not alone in your 23andMe discovery of GSD raw data SNP's discovery. Mine are in PYGL=GSD-6 and in G6PC=GSD-1a. There exists literature in medical journals finding correlation between GSD, FBPaseD, and HFI. All 3 involve the same digestive pathway and are very closely related at the top of the pathway.

[christopher]

Thanks you guys. Still finding it difficult to understand what to make of this. But I at least find it interesting that I seem to have the "rarer" kind of mutations in several of the genes that code for different kinds of GSDs, but especially those that according to the literature I´ve read seems to benefit from a high protein diet. Those would be GSD III, IV, VI, and IX. So yeah, there is a bonus mutation there as well. 

Edit: correction.. Two bonus mutations! 

[tummyache]

I checked on dbSNP the SNP's you gave and all have "clinical significance = NA". Of interest, is the SNP for GSDXII [rs238239], also named Val85Ala, which might mean it has some special significance, or it might just been studied more -- I don't know? Anyway, I have a number of these "NA" SNP's, marked +/+ [red] on Livewello just like you. However, the SNP's of real importance showing positive disease [but unreported on Livewello] are the ones marked "Pathogenic" or "Likely Pathogenic". The actual clinical significance of the red ones Livewello reports on are questionable...and only a genetic specialist is qualified to tell us for sure.

[christopher]

Wow, thanks tummyache! Yeah, 23andme seems to sensor most of the pathologic sNPs, giving them an internal reference number starting with an "i" instead. As such, I did some more digging while focusing on the "i" numbers, for my AGL (GSD III) gene.

I used the Kaviar tool (http://db.systemsbiology.net/kaviar/) and believe I might have found something interesting, but then again I am no geneticist.
Using Kaviar, one can find the different variants and reference variations simply by providing the position of the sNP. I found the following two variations interesting:

AGL position 100316616 - 23andme reference number: i5012654. My result is: II (a double deletion?)
according to Kaviar the reference is AG for both position 100316615 and 100316616. By DELETION the number (0.0006%) appears. Would this be the incidence number for the deletion variation?)
www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=794727255 - lists this as a pathologic sNP. The question is if my deletion of the ...16 position is sufficient for the disease to occur? (didnt get any info on the ...15 position)


AGL position 100343347 - 23andme reference number i6034662. My result is: II (another double deletion?)
According to Kaviar the reference is T. By DELETION the number (0.0013%) appears.
www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=765447247 - doesn´t give any info on this variation´s significance. But if fI am not mistaken, it is at least quite rare...

Any feedback on this, anyone?

[tummyache]

Actually, "II" means "double insertion", while "DD" means "double deletion". My guess would be in both cases a "DD" would signify the Pathogenic SNPs not "II".

[christopher]

Thanks Tummy, I agree. 

What about these ones, tho? I compared with a friends results and he didn´t seem to have both of these sNPs at the same genomic position as I have.



According to Enlis (which I just installed and ran. Hello 21-hydroxylase-deficiency, by the way...) the range deletion is same as reference, but the software does not report on the ...82 in isolation. How can there be two different sNPS concerning the same position anyways? 

[tummyache]

I think you really need to be asking these questions of a genetics specialists. Hopefully you can get a professional answer in your quest to find a sure diagnosis -- HFI, GSD, FBPaseD -- and how it's all related.

[carolyn]

I struggled to get people in the medical profession to take HFI seriously and for most of my life I have felt unbelieved regarding my HFI symptoms. After genetic testing and finding that I have two genetic variants for the disorder I am at last being listened to!! Finally got a referral to a dietician.....at the tender age of almost 58..!! I hope you get some answers to your queries Christopher. Keep us posted!

[colormist]

Congrats on your long fought success, Carolyn! I felt extremely lucky that the first doctor I talked to believed me. The doctor she referred me to, did not believe me--but he did humor me with a genetic test. Some doctors have difficulty believing that you will be the 1 in 20,000 who have this condition.

[ukbill]

Carolyn good luck with the dietician. never found them one ounce of good myself.. although I do hear of some people they have helped.
I can send you the fixed food list (the original was dangerous to HFI people) given out by the top Genetic hospital in the UK if that helps?
With some foods its the way its prepared and cooked that makes the difference between it being relatively safe and quite unsafe.
Christopher the standard human diet today is full of fast digesting high energy level foods.

For example white flour sugar processed foods that remove fibre or just "smoothies" which although the fiber is still there it's made useless by the blending process.

So a high protein diet that slowly is digested rather than the instant "kick" of sugar is going to be far healthier for everyone and in particular almost anyone with any sort of digestive issues.

Modern food for humans is like running your motor on racing gas.. it runs harder but has a shorter life as a result.


However you will need to find some fiber to help keep your gut working smoothly too. I always suggest Psyllium husks because they are not digestible (in whole form I suspect more digestible in the fine ground version)
If eaten with plain probiotic Yogurt (if you can take this?) it provides a platform for the bacteria to live on while it passes through the gut and really helps me a lot.

Hope this helps ??

Keep smiling

Bill A.

[oneladyff]

I have not found a single dietician that does not hand me a list of foods that are completely unsafe for me. I don't understand how they come up with their lists. Nuts, asparagus, avocados are not good for me but yet on all the lists. I believe they just don't know. Sad

[ukbill]

The Safe foods list given out by the leading UK hospital working on HFI and related sugar issues is potentially lethal to a child if fed off the list insensitively.

[antonia]

Hello Christopher. I'm sorry I don't know a darn thing about these genetic tests, but I was just wondering how you are doing. At an appointment with my daughter's geneticist we discussed one type of GSD (he did not say what type specifically) that can mimic HFI, the difference being that the problem exists with ALL sugars, even lactose, which HFIers of course do not have a problem with because lactose contains no fructose (thankfully!). My daughter does fine with lactose so we never investigated it. Are you still doing better with your high protein diet? Do you, or did you, ever have issues with lactose? Hoping you are getting closer to a diagnosis.

[ukbill]

Nov 20, 2016 0:58:00 GMT -5 oneladyff said:

I have not found a single dietician that does not hand me a list of foods that are completely unsafe for me. I don't understand how they come up with their lists. Nuts, asparagus, avocados are not good for me but yet on all the lists. I believe they just don't know. Sad

Have you got any further with your diet? Do you want me to send you my amended Diet sheet which is far safer than the "official" one?


amended Addenbrooks food list.-1.doc (99 KB)

Well here it is anyway hope this helps?

Keep smiling