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March20 podcast Dr Hazen
anti-TMA pill in a year or 2 ? (scroll 12 mins)

Additional info: https://youtu.be/811v7RLXP9M
MEBO Karen
at UK Findacure conf 2020

Scroll down and select country
MEBO TMAU TESTING DISCONTINUED
(2012-2017)

MEBO Map Testing & Meetups


Full details : https://goo.gl/TMw8xu
want listed ? contact info@meboresearch.org

MEBO - UBIOME study 2018

'PRESS RELEASE'

NCT03582826
ClinicalTrials.gov

MEBO Gut Microbiome Study
"Microbial Basis of Systemic Malodor and PATM Conditions (PATM)"
Funded by uBiome Research Grant

"Microbial Basis of Systemic Malodor and PATM Conditions (PATM)"

Dynamics of the Gut Microbiota in
Idiopathic Malodor Production
& PATM

Started May 2018 - Ongoing

Current people sent kits : 100/100
3 kits per person

NO LONGER RECRUITING

Participation info : LINK English

MEBO Private Facebook Group
to join : go to
or contact
Join/Watch the weekly
BO Sufferers Podcasts

MEBO TMAU Videos

Petitions

TMAU Petition world
TMAU UK end total:262
TMAU UK ends 23/01/20
TMAU Petition USA end total 204
USA : Moveon open
TMAU (Dominican)
Metabolomic Profiling Study
NCT02683876

Start : Aug 2016
Stage 1 : 27 Canadian volunteers to test
Latest click here (26 oct) :
17 samples returned


Note : Stage 1 is Canada only.
Return cut-off date : passed
Analysis can take 6/8 weeks
Analysis start in/before Nov
MEBO Research is a
EURORDIS and
NORD Member Organization
See RareConnect
rareconnect.org TMAU

Popular Posts (last 30 days)

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Blog Archive

MEBO Metabolic Malodor Survey (international) for Dr Hazen click here
click to Read more/less

survey for ANYONE who identifies with METABOLIC MALODOR

begun : Oct20
end : no ending for now

Regular readers will know that Dr Stan Hazen et al at Cleveland Clinic are developing a TMA-blocker pill, as they proposed in a 2011 paper that TMAO is a factor in CVD. Recently Dr Hazen and colleagues contacted MEBO as they have always thought they could also help with TMAU. This survey is to give them an idea of the 'state of the community'. It is a "version 1". They may not even look (though they have access permission), but it could be useful to give them an overview of the community

MEBO had a zoom call with Dr Hazen and his team in October. Another zoom call is planned when they have time

This is a GOOGLE FORMS survey

short url for survey :
https://forms.gle/vem2TjepKobYZPBu8

current participants : 113 (update 18dec20)

Monday, April 8, 2019

New TMAU paper from Eileen Treacy (test results via Sheffield)

Dr Eileen Treacy is an Irish Metabolic Consultant who has long had an interest in TMAU.
This includes while working at McGills Canada (who TMAU test) and now in Dublin.

3 new FMO3 mutations identified
Dr Treacy has lead a new study using test stats from some Irish patients, using Sheffield TMAU test lab.
From 13 people deemed TMAU1 (genetic TMAU), they found 3 new FMO3 variants that will likely affect FMO3 funtion (negatively).

Note about Sheffield lab (did they use the old test method ? i.e. done before 2017 ? )
It seems Nigel Manning is thanked in the acknowledsgments, which may mean the Urine Test was done using the old (more believable results ???) test method (pre-2017).
The new Sheffield method is similar to Denver and gives half less positive TMAU1 cases than the old test (from 33% down to 18%). 

So little known about FMO3 variants/mutations
This shows how little is documented about FMO3 variants/mutations, that 3 can be found easily from such a small group. How many more are to be disscovered.

Excellent 'cheap' study
This shows what can be discovered from a study as simple as looking at the test stats of 13 positive results. Test stats are so vital information for a disorder not heard of by most.
It would be great if say UCLH (The Charles Dent Metabolic Clinic) or Denver followed suit.


The genetic and biochemical basis of trimethylaminuria in an Irish cohort      
Full paper (Wiley Journal)

Samantha Doyle1,4|  James J. O'Byrne1|  Mandy Nesbitt2|  Daniel N. Murphy3|Zaza Abidin1,4|  Niall Byrne1,4|  Gregory Pastores1,4|  Richard Kirk2|Eileen P. Treacy1,4,5

1. National Centre for Inherited MetabolicDisorders, The Mater MisericordiaeUniversity Hospital, Dublin, Ireland
2. Sheffield Diagnostic Genetics Service,Sheffield Children's NHS Trust,Sheffield, UK
3. National Rare Diseases Office, The MaterMisericordiae University Hospital, Dublin,Ireland
4. School of Medicine and Medical Sciences,University College Dublin, Dublin, Ireland
5. Department of Paediatrics, Trinity CollegeDublin, The University of Dublin, Dublin,Ireland

Quotes from paper

Results:
A genetic diagnosis was made for seven patients, including for five of the nine moderate to severely affected cases. We noted the c.913G>T;p.(Glu305*) and c.458C>T;p.(Pro153Leu) mutations in this Irish population with severe TMAU which is consistent with our earlier findings in Australian and North American families of Irish and British descent.Three individuals were noted to be homozygous for the common variant haplotypec.472G>A;923A>G;p.(Glu158Lys);(Glu308Gly). We also identified three novel variants in this population, which are likely to be pathogenic: c.682G>A;p(Gly228-Ser), c.694G>T:p(Asp232Tyr), and c.989G>A;p.(Gly330Glu) ...

...The polymorphic haplotypes are prevalent in the popula-tion with undetermined penetrance. As the majority of indi-viduals carrying these common variants are likely to beasymptomatic, it may not be beneficial to identifyFMO3variants, which results in mild TMAU, which could leadto detrimental over-restriction of choline and other self-imposed dietary imbalances.

Interesting points :

FMO3 protein is made from a 532 amino acid sequence.
3 nucleotides make up an amino acid.
In DNA test they look at the Nucleotides, and so can work out the amino acid that will be made.

The 5 most common FMO3 'variants' (bracket = guestimation of commoness of variant)

FMO3 codon/amino acid (of 532)
158 (maybe 40% people ?)
285 (26%?)
308 (20% ?)
257 ( 8% ?)
147 (6%?)

So FMO3 variants are common.
The question then is why do some end up as a 'smell-risk' since e.g. 40% of people do not have TMAU ?

The taught theory is that only those who carry the same variant on both sides (homozygous) and it is a severe variant will be affected (e.g. 153-153)

Most are a mix of more than one variant ?
Another theory could be that 'severe' and most 'high-risk mild' people might carry 2 or more variants ?
e.g.
Carrying a severe mutation (alone ?) and 1 or more common variants.
Carrying 2 or more common variants ?
(note: Dr Treacy would probably not agree with this theory).

We thank Dr Treacy and Sheffield Children's Hospital for this important study.

This is possibly the first TMAU/FMO3 'stats' paper in 10 years.
It would be very helpful if test labs published the test stats, but this seems currently unlikely.
One aim for the community could be to get politicians to tell them to publish the stats (e.g. twice a year, yearly)

Links
Clinical Utility Card entry for TMAU 
Prof Elizabeth Shephard FMO3 Variant Database

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A EURORDIS and NORD Member Organization

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