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CBS gene mutations being investigated in Ehlers-Danlos. 
Posted: 14 December 2012 01:51 AM   [ Ignore ]  
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I have two CBS mutations. When I looked the CBS genes up it was noted they are being investigated in…. Ehlers-Danlos!
CBS gene mutations are involved in methylation.

What is “The Methylation Pathway”?????:
http://www.autismnti.com/yourbodyschemistry.html

http://snpedia.com/index.php/Yasko_Methylation
“CBS Gene
rs234706 - CBS C699T (Risk Allele: A) “Being investigated in Ehlers-Danlos syndrome”
rs1801181 - CBS A360A (Risk Allele: T, 23andMe: A) “Being investigated in Ehlers-Danlos syndrome”
rs2298758 - CBS I278T (Risk Allele: G) “Being investigated in Ehlers-Danlos syndrome”

“CBS Gene: Limits homocystine into downstream path. People with CBS mutations will need to be careful with sulfur containing supplements. Increased risk for ammonia detoxification issues. Puts a burden on SUOX.”
http://snpedia.com/index.php/Rs234706
http://snpedia.com/index.php/Rs1801181
http://snpedia.com/index.php/Rs2298758

This is a Gene test for Marfan/TAAD which is listed under the heading “Ehlers-Danlos” and it includes CBS.
http://www.genedx.com/test-catalog/disorders/ehlers-danlos-syndrome/marfan-syndrometaad-sequencing-panel/
Genes on this test: ACTA2, CBS, COL3A1, COL5A1, COL5A2, FBN1, FBN2, MYH11, SLC2A10, SMAD3, TGFBR1, TGFBR2

Read more about CBS mutations:
http://www.heartfixer.com/AMRI-Nutrigenomics.htm

Anyone else have CBS mutations?

Dr. Diana, do you think the sulfur load could be similar to a barrel effect like with histamine?  Maybe some patients who haven’t done well on Diamox have CBS mutations and are already over-burdened with sulfur. I wonder if they limited other sulfur sources and got their methylation working better if they might be able to tolerate the Diamox?  Hmmmm…. I haven’t tried it yet because I’m so allergic to… sulfa antibiotics but maybe a trial under my allergist’s supervision will be in my future after all. Thoughts?

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Posted: 14 December 2012 02:31 AM   [ Ignore ]   [ # 1 ]  
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http://www.genecards.org/cgi-bin/carddisp.pl?gene=CBS

“OMIM gene information: 613381   OMIM disorders: 236200
UniProtKB/Swiss-Prot: CBS_HUMAN, P35520
Defects in CBS are the cause of cystathionine beta-synthase deficiency (CBSD) [MIM:236200]. CBSD is an
enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria. The clinical features of untreated
homocystinuria due to CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling
Marfan syndrome, and thromboembolic events. Light skin and hair can also be present. Biochemical features include
increased urinary homocystine and methionine.”

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Posted: 15 December 2012 04:29 AM   [ Ignore ]   [ # 2 ]  
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Sweet feather : Is diamox contra indicated if one has sulpha allery?

Weirdly I have sulpher antibiotic allery too and Johns Hopkins pediatricain said I had EDS, but NZ geneticist said I didn’t tick enough boxes but then he didn’t know about the POTs in EDS either, nor the sleep apnea in Marfans I’m guessing. My Al (whi I suspect has marfans , is seeing same geneticist so I hunted the net to find out what tests they *should * do, one was a sleep study. Apparently a lot of Marfans have apnea - not snoring kind though.

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Posted: 15 December 2012 09:16 AM   [ Ignore ]   [ # 3 ]  
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I have sulfa allergy (sidenote).

Re:  MTHFR:  I have both high homocysteine and high B12 - chronically.  It appears that these two phenomenon do not coexist.

Any suggestions?

Among other bloodwork abnormalities.

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Ehlers Danlos Syndrome, Fibromyalgia, Cardiomyopathy and other heart abnormalities, IBS, Neuropathy, Osteoarthritis, Hypothyroidism, TMJ (bilateral disk replacement w/autologous fat transplant), Asthma, Chronic sinusitis (remediated by successful FESS), Reversed Cervical Lordosis, Spondylosis, Kyphosis, Thrombophlebitis, CFS, and it’s probable that much has slipped my mind.  I haven’t been diagnosed with Dysautonomia but, personally, feel certain that this is playing a part in daily struggles

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Posted: 15 December 2012 01:19 PM   [ Ignore ]   [ # 4 ]  
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jiiiMEnz, I’m hoping Dr. Diana will have a chance to chime in here! She has said that some with sulfa allergies tolerate it but you must discuss this with your physician and let them decide if you could do a doctor-supervised trial.

A PubMed search:

Evidently, “It’s a not so simple story”

http://www.ncbi.nlm.nih.gov/pubmed/21190500
High Alt Med Biol. 2010 Winter;11(4):319-23. doi: 10.1089/ham.2010.1051.
“Acetazolamide and sulfonamide allergy: a not so simple story.”
“We also examine the different clinical presentations of allergy and adverse reactions, from simple cutaneous reactions with no sequelae through Stevens-Johnson syndrome and anaphylaxis, with risk for significant morbidity and mortality. We offer a systematic approach to determine whether acetazolamide is a safe option for those with a history of allergy to sulfonamides.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1783707/
Can Fam Physician. 2006 November 10; 52(11): 1434–1438.
PMCID: PMC1783707
“Approach to managing patients with sulfa allergy.”

 

 

 

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Posted: 15 December 2012 03:00 PM   [ Ignore ]   [ # 5 ]  
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Give My Daughter The Shot!,  23andMe testing just dropped to $99 plus shipping because they’ve received $50 million in additional funding and they are trying to reach a million people. The NIH recently awarded them over a half million dollars for three research projects… one on allergy and asthma. YAH!!!!

I had dismissed MTHFR before…. thinking “neural tube defects don’t run in my family” but the methylation pathway involves so much more than MTHFR and neural tube defects. Homocysteine and B12 are involved and having high levels of both… can be an indication of MTHFR and other methylation pathway mutations.

Google:
Dr. Amy Yasko (she’s the main researcher behind the methylation pathway and whose protocol is the base for the other “simplified” versions) she has videos, testing, proprietary and other supplements.) Her book “Autism: Pathways To Recovery” is free for download on her website. Methylation Pathways mutations don’t just cause autism… it depends on when the methylation pathway breaks down! Her previous book was called “Genetic Bypass” and I think she’d reach more people with a title like that but because autistic kids are so sick she’s concentrating on helping getting them well. She’s a bit controversial because of her extensive supplement regime but her research is the basis for all the other protocols. 

Also:
Dr. Stephen Smith MD of NW Integrative Medicine (see his website for a video on MTHFR and Glutathione and a link to his two mind maps at mindmeister.com on MTHFR symptoms and treatment) (His video says at 3:09 that B12 is usually high in people with MTHFR “because they just can’t convert it”)

Dr. Neil Rawlins MD: watch his 4 part you tube video and see his “simplified protocol” (Methyl-life.com’s “Resources” has his links among others)

Dr. Ben Lynch (watch his you tube presentation and read his website Mthfr.net ... he sells “Seeking Health” supplements (see: “MTHFR C677T Mutation: Basic Protocol”)

Dr. Rich VanKonynenburg Ph.d (chronic fatigue researcher… sadly he recently passed away. His simplified protocol is at the “Phoenix Rising” Forum, Dr. Smith has a link to his videos)

Phoenix Rising.me’s forum under “Detox: Methylation; B12; Glutathione; Chelation” has Dr. Rich VanK’s “simplified methylation protocol” and a poster named “Freddd” has developed a B-12 treatment plan. There’s a lot of info on this site!

Dr. James Roberts (cardiologist who uses Yasko’s testing has outlined possible treatments based on Yasko… see “Heartfixer nutrigenomics”

April Ward-Hauge MS, NP, BCIM: Nutrigenomics & Integrative Medicine (see “Your Body Chemistry” for an easy to understand explanation of methylation.)

Dana at danachronicallyliving’s blog developed a spreadsheet… see “Determining Your Yasko Methylation Results from 23andme Data”

“Genetic Genie dot org” used Dana’s spreadsheet as the basis for their conversion programming.

Google: High Homocysteine and MTHFR at PubMed

I did the 23andMe and I ran my results through “Genetic Genie.” The CBS mutations were the tip of the iceburg. I found I have over a dozen mutations in the “methylation pathway” and a hemochromatosis gene!!! (BTW, anyone with elevated liver enzymes… one cause often missed is hemochromatosis… google iron disorders.org)

I contacted Sterling Hill of MTHFR SUPPORT through her facebook and scheduled a consult to have her analyze my data. She found other genes which may be indicated in chronic illness and she taught me how to do more research on my 23andMe raw data using SNPedia and 1000 genes. Her fee was very reasonable and I HIGHLY recommend her!!!!!

My 23andMe only took a couple of weeks to get results… it may take longer now because so many people already on there are having multiple family members tested since the price dropped from $299.  See MTHFR SUPPORT for Sterling’s comparison of Yasko and 23andMe’s testing and the other genes relating to chronic illness to help you decide if you want to go with Yasko or 23andMe or do both.

My best, SweetFeather

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Posted: 17 December 2012 01:32 PM   [ Ignore ]   [ # 6 ]  
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Thanks for sharing Issie! Have you tried low carb grain free? My resting heart rates dropped an average of 20 points following a low carb grain free diet. That showed me that keeping insulin and leptin in control is critical for me to minimize my brain inflammation. That coupled with learning researchers want to rename alzheimer’s “type 3 diabetes” helps keep me motivated to keep carbs low. But with CBS too much protein can be a problem… because of sulfur!!! What to do???? What to do????  I love Maria Emmerich’s blog for her coconut flour and almond flour recipes. I’m looking for a provider who knows how to deal with CBS mutations because according to Dr. Yasko they must be addressed first. Please PM me if you have any suggestions. Thanks! My best, SweetFeather

PS. Issie did you check for celiac markers? Sterling Hill of MTHFR SUPPORT found I have several celiac markers… I’ve been gluten free for three years but if I’d known this earlier it could have made a huge difference in my health. I had NEGATIVE tests for celiac so those aren’t always accurate and even a biopsy can miss it…  I had a postive response to diet and now I have genes to check for in my kids.

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Posted: 17 December 2012 03:42 PM   [ Ignore ]   [ # 7 ]  
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SweetFeather - 15 December 2012 01:19 PM

jiiiMEnz, I’m hoping Dr. Diana will have a chance to chime in here! She has said that some with sulfa allergies tolerate it but you must discuss this with your physician and let them decide if you could do a doctor-supervised trial.

A PubMed search:

Evidently, “It’s a not so simple story”

http://www.ncbi.nlm.nih.gov/pubmed/21190500
High Alt Med Biol. 2010 Winter;11(4):319-23. doi: 10.1089/ham.2010.1051.
“Acetazolamide and sulfonamide allergy: a not so simple story.”
“We also examine the different clinical presentations of allergy and adverse reactions, from simple cutaneous reactions with no sequelae through Stevens-Johnson syndrome and anaphylaxis, with risk for significant morbidity and mortality. We offer a systematic approach to determine whether acetazolamide is a safe option for those with a history of allergy to sulfonamides.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1783707/
Can Fam Physician. 2006 November 10; 52(11): 1434–1438.
PMCID: PMC1783707
“Approach to managing patients with sulfa allergy.”

Great find, Sweetfeather!!! On Prettyill’s Facebook, we had a pretty LONG discussion about MTHFR. You may have seen my video—my family is not affected with any MTHFR mutations. I believe it is but one cause of blood stagnation and toxin build-up which can cause the start of some of our issues. Please remember that many people do NOT have issues with this defect, yet still suffer with POTS/hypermobility. So I think we need to cast our net a bit wider. If you are negative for MTHFR defects, PLEASE check for other causes of “blood thickening”, OK? Thanks for the great info! wink Diana

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Posted: 17 December 2012 04:32 PM   [ Ignore ]   [ # 8 ]  
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Thanks, Dr. Diana! I missed the facebook discussion so I’ll check that out. I did see your video. I’m so glad you and your kids don’t have any methylation pathway mutations… I had twelve and two are homozygous! I know it is NOT the end all be all…. just part of the puzzle for me. I know the answer isn’t down any one rabbit trail and having spoken to you on the phone… I know you are going to have more answers for us soon. Blessings to you and yours this holiday season! Big Hugs! SweetFeather

 

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Posted: 17 December 2012 11:00 PM   [ Ignore ]   [ # 9 ]  
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TWELVE!!! I’ll bet it’s busy around your household!!! OMG… wink

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Posted: 19 December 2012 07:44 PM   [ Ignore ]   [ # 10 ]  
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Hi Issie and all, Just a thought… Most of us need to watch our food intake, go on special diets, etc. That’s hard. BUT WHAT ABOUT OUR KIDS? Yikes. Trying to explain the importance of dietary restrictions to teens is TOUGH. And they are at that “I’m invincible” age at our house. Any body else deal with this? Pills and diets at a tender young age. It’s soooo hard… smile Diana

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Posted: 20 December 2012 08:10 PM   [ Ignore ]   [ # 11 ]  
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Great advice and thoughts, Issie! It seems I’ve always “eaten well” and I wonder if it is because, subconsciously, my body figured out that it did better… When the kids don’t notice the difference until the next day, though, it’s TOUGH!! I have noticed that my son likes air-popped popcorn, basically every day. I used to TRAVEL with my popper!! Certainly, it is a food that gives us NO problems. I suppose he is figuring it out… Thanks, Hon smile

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Posted: 05 February 2013 08:13 AM   [ Ignore ]   [ # 12 ]  
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SweetFeather - 14 December 2012 01:51 AM

I have two CBS mutations. When I looked the CBS genes up it was noted they are being investigated in…. Ehlers-Danlos!
CBS gene mutations are involved in methylation.

What is “The Methylation Pathway”?????:
http://www.autismnti.com/yourbodyschemistry.html

http://snpedia.com/index.php/Yasko_Methylation
“CBS Gene
rs234706 - CBS C699T (Risk Allele: A) “Being investigated in Ehlers-Danlos syndrome”
rs1801181 - CBS A360A (Risk Allele: T, 23andMe: A) “Being investigated in Ehlers-Danlos syndrome”
rs2298758 - CBS I278T (Risk Allele: G) “Being investigated in Ehlers-Danlos syndrome”

“CBS Gene: Limits homocystine into downstream path. People with CBS mutations will need to be careful with sulfur containing supplements. Increased risk for ammonia detoxification issues. Puts a burden on SUOX.”
http://snpedia.com/index.php/Rs234706
http://snpedia.com/index.php/Rs1801181
http://snpedia.com/index.php/Rs2298758

This is a Gene test for Marfan/TAAD which is listed under the heading “Ehlers-Danlos” and it includes CBS.
http://www.genedx.com/test-catalog/disorders/ehlers-danlos-syndrome/marfan-syndrometaad-sequencing-panel/
Genes on this test: ACTA2, CBS, COL3A1, COL5A1, COL5A2, FBN1, FBN2, MYH11, SLC2A10, SMAD3, TGFBR1, TGFBR2

Read more about CBS mutations:
http://www.heartfixer.com/AMRI-Nutrigenomics.htm

Anyone else have CBS mutations?

Dr. Diana, do you think the sulfur load could be similar to a barrel effect like with histamine?  Maybe some patients who haven’t done well on Diamox have CBS mutations and are already over-burdened with sulfur. I wonder if they limited other sulfur sources and got their methylation working better if they might be able to tolerate the Diamox?  Hmmmm…. I haven’t tried it yet because I’m so allergic to… sulfa antibiotics but maybe a trial under my allergist’s supervision will be in my future after all. Thoughts?

Hi,
Thank you very much for posting this SweetFeather.

Using 23andme my wife found out she is homozygous positive for the C699T CBS mutation and the A1298C MTHFR mutation.

It’s very interesting to me to see that CBS is being investigated for its role in EDS.  I wish there was more of a description re who/what/where is being investigated, but I guess it will be published eventually if any of the investigations are fruitful.

I just want to clarify something I saw.  I think there are two different ways that CBS mutations can affect the methylation cycle are being mentioned in your links though. 

The link relating to the Marfan Syndrome genetic test I believe is (partly) testing for a mutation in the CBS gene that involves downregulation of CBS and can cause elevated levels of homocysteine and is seen to be responsible for a condition called Homocystinuria that has overlap w/ Marfan (see here, http://www.ncbi.nlm.nih.gov/books/NBK1335/, and here, http://www.ncbi.nlm.nih.gov/books/NBK1524/ - I arrived at these links from the Marfan testing link you posted). I believe those studies refer to the 833T>C and 919G>A mutations of the CBS gene.

The mutations referred to by Dr. Amy Yasko are Y233Y (C699T) and A360A.  Yasko says that these mutations involve an upregulation of the CBS gene and that “It’s not surprising that in those with the CBS mutation it’s common to see low levels of homocysteine, cysteine, or cystathionine, due to the rapid conversion to taurine.”

It seems like if these mutations are part of the problem and need addressing, then the directionality of regulation is important.

We’ve only just started on looking into treatment for this, and are planning to read through all of Yasko’s book.

 

 

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Posted: 05 February 2013 11:58 AM   [ Ignore ]   [ # 13 ]  
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Hi everyone, there is SO MUCH great info here! I do believe that our illnesses are shaped by our genes, certainly, and recommend that everyone get a 23andme (now at $99). As we gather all of this info together, obviously it will be critical to know where your weaknesses are. I think it is entirely possible that Diamox may not agree with folks who can’t handle the overload of sulphur. Concerning sulphur allergies, I DO hear that most folks do fine with Diamox, even with a sulphur allergy, but obviously, you and your doctors will want to be careful with that, certainly. Some doctors (usually allergists) can put you through a desensitization program so that you can tolerate most anything. I think that may be important, because we don’t really have a non-sulphur alternative to lower our intracranial pressure, dad gum it. In our family, we have low homocysteine, and our 23andme results are sitting here for me to check for CBS mutations. They’re still patiently waiting! Our family is negative for MTHFR defects, so methyllation went to the back burner. I’ll revisit it, certainly, just as soon as I can get to it! I’m happy to share my results, as soon as I figure them out, BTW! wink Interesting that they put TGFBR1 and TGFBR2 in with the mix for CBS mutation tests… That is the test for Loeys-Dietz syndrome (we tested negative for this). If they are checking other collagen disorders (not just EDS), I wonder if these other genes include ones for Sticklers, etc? As soon as I wrap up these two patents I’m working on, this will be next on my list! Thank you all for such wonderful info!! Big hug…

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