Tuesday, July 7, 2009

New FMO3 paper : Norwegian family with novel FMO3 mutation

Another FMO3 paper was published on pubmed this week. This one involves Phillips and Shephard of London, who have a long history in FMO3/TMAU research. The paper is an observation of a Norwegian Family carrying an FMO3 mutant (a new one). Sadly this type of anecdotal paper makes up the bulk of FMO3/TMAu research. Especially recently; as opposed to big trials making breakthroughs.

The paper also shows the gap between researchers and sufferers, since the girl seems to have presented with a body odor problem, but since she doesn't fit the strict definition of TMAu by DNA (i.e. autosomal recessive) they are predicting her as a 'childhood' case. We will only be able to see if this is the case in 10 years or so.

She seems to have one copy of a 'new' severe mutation, which her mother also had a copy of. Her father seemed to have 2 other variant copies of FMO3, but she hadn't received either of them (?)

It again highlights the gray area of defining TMAu. At the moment researchers will try to shoehorn the definition into their own strict rules. Meanwhile the patient either has a transient smell problem or not. If they do have a smell problem, then the patient is the correct definition and the rules need changed (in this case we need to wait and see).

In the end, they at least found yet another 'novel' mutant to add to the list of mutants. How many more of these mutants will be found is unknown, but most of these anecdotal papers seem to be new mutants nowadays.

A novel mutation in the flavin-containing monooxygenase 3 gene (FMO3) of a Norwegian family causes trimethylaminuria


Allerston CK, Vetti HH, Houge G, Phillips IR, Shephard EA.

Institute of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London WC1E 6BT, UK.

Loss-of-function mutations in the flavin-containing monooxygenase 3 gene (FMO3) cause the inherited disorder trimethylaminuria (TMAuria), or fish-odour syndrome. Here we describe the identification in a family from northern Norway of a novel causative mutation of TMAuria. A female child within the family presented with a TMAuria-like phenotype. The child and her mother were found to be heterozygous for a novel mutation (R238Q) in exon 6 of FMO3. The child's father lacked this mutation, but was heterozygous for a double polymorphic variant, E158K/E308G, which was not present in the child. During a consultation with her doctor the mother mentioned an uncle whom she remembered as having a strong body odour. This discussion led to genetic counselling of the uncle and analysis of his DNA showed him to be homozygous for the R238Q mutation. Analysis of the mutant FMO3 expressed in bacteria revealed that the R238Q mutation abolished catalytic activity of the enzyme and is thus a causative mutation for TMAuria. The specificity constant (k(cat)/K(M)) of the K158/G308 variant was 43% of that of ancestral FMO3. Because the child is heterozygous for the R238Q mutation and no other mutation known to cause TMAuria was detected in her DNA she is predicted to suffer from transient childhood TMAuria, whereas her great-uncle has primary TMAuria.

http://www.ncbi.nlm.nih.gov/pubmed/19577495

related links:
NIH GeneReviews page on trimethylaminuria
Pubmed search : Shephard EA
Professor EA Shephard UCL page
Pubmed search : Phillips IR

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Sunday, July 5, 2009

Latest FMO3 research paper : Japanese FMO3 Inter-individual variation

This is the latest FMO research paper published on pubmed, from a group of Japanese researchers at Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Tokyo, Japan. There doesn't seem to be any significant finding, other than Japanese livers seem to vary for FMO3 as much as Caucasians ? The researchers probably reearched under the perspective of FMO3 being a 'drug metabolizing enzyme', and it is likely a small % of their work. They seem to be drug metabolism researchers (pharmacokinetics) and so will FMO3 is likely a low priority to them.

FMO3 enzyme is regarded as the enzyme saturated in the case of trimethylaminuria. It is part of the group of 'xenobiotic metabolizing enzymes' which are also the main 'drug metabolizing enzymes', although FMO is still largely perceived as unimportant by medical researchers (in comparison to the other enzymes in the group). There have been around a dozen pubmed entries on FMO3 this year

Inter-individual variation in flavin-containing monooxygenase 3 in livers from Japanese: correlation with hepatic transcription factors.

Nagashima S, Shimizu M, Yano H, Murayama N, Kumai T, Kobayashi S, Guengerich FP, Yamazaki H.

Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Tokyo, Japan.

Human flavin-containing monooxygenase 3 (FMO3)-mediated microsomal oxygenation activity, levels of FMO3 protein and FMO3 mRNA and modifications were investigated in Japanese livers genotyped for the FMO3 gene. Significant correlations were observed for benzydamine N-oxygenation or methyl p-tolyl sulfide S-oxygenation activity (in the range of approximately 20- to approximately 40-fold) and FMO3 levels determined immunochemically in liver microsomes (r(2)=0.73-0.75, p less than 0.0001, n="16)." p="0.0010," n="16)," p="0.0017," n="37)."

pubmed abstract

The full paper in PDF format can be downloaded on this page :
Inter-individual variation in flavin-containing monooxygenase 3 in livers from Japanese

body odorrelated links:
more about FMO3 on NIH page

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Wednesday, July 1, 2009

Introducing the Los Angeles Support Group

INTRODUCING THE LOS ANGELES SUPPORT GROUP
Hi this is Joel. It is my pleasure to introduce the Los Angeles TMAU Support Group. The mission of the support group is to offer its members the ability to connect and get to know other members in person and to share tips and methods to deal with the daily struggles of living with TMAU and other Chronic Body Odor Issues. Our hope is that by doing so we can help improve the lives of those living with TMAU and Non TMAU disorders. The LATSG will meet once a month. A significant amount of time will be set-aside to allow members to share themselves with one another. Then we will focus on one or two aspects of living with TMAU and how we can improve that part of our lives.

Everyone is Invited
The mission of the support group is to offer its members the ability to connect...to share tips and methods to deal with the daily struggles of living with TMAU and other Chronic Body Odor Issues.Topic: This upcoming meeting will not have a specific topic. It will serve to build unity among our members. Please come with an open mind and ready to share. Remember, you must give in order to receive.


Our next meeting will be held at:

Date: July 25th, 2009. Saturday

Time: 12:00 PM Noon

Place: Arcadia Community Regional ParkThe park is about 1 mile away from Santa Anita Race Track. You can get to the park via the 210 freeway, exit Santa Anita Ave and head south. The park is located at the corner of Huntington Dr. and Santa Anita Ave.

Address: 405 South Santa Anita Avenue, Arcadia, CA 91006. Park your vehicle in the huge parking area off Santa Anita Ave.


To prepare people for this meeting we will have a conference call on:

Date: July 11th, 2009. Saturday
Time: 11 AM (Pacific Standard Time)
Conference Dial-in Number: (712) 432-1620
Participant Access Code: 391629#


Contacting Joel:
Cell: (213) 300-7589
Email: joelm211@yahoo.com

Body Odor Support Group (BOS)

http://health.groups.yahoo.com/group/Trimethylaminuria/

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Tuesday, June 30, 2009

New TMAU support website in the UK

Poster "big vern" recently posted on the curezone TMAU forum that he has started a UK-based TMAU website. Although it is UK orientated, TMAU is a universal problem and so will be one to save in your favorites/bookmarks. It also has a forum that anyone can join.

The site is support-group orientated, and as it says :

Bringing together people who have Trimethylaminuria , their families, friends and healthcare professionals in a positive, caring and supportive environment.
body odor ukhttp://www.tmau.org.uk/

It also has a TMAU forum

It's good to see so many metabolic body odor websites now making an appearance on the internet

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Sunday, June 28, 2009

Upcoming events discussed in our Conference Calls


In today's conference call, we talked about:

1. Systemic hyperhidrosis and bromhidrosis: Compensatory sweating and odor after surgery affirms that the cause of this condition is of an internal, systemic source.

2. Compilation of data: As a community, our goal is to compile data of our symptoms and possible triggers to look for patterns as the initial step for formal scientific research. All are encouraged to participate in MeBO and Arun's upcoming projects to achieve this goal.

3. Our 2009 Thames Festival Meet-Up: to take place on Saturday, September 12th and Sunday, September 13th in London –
a. Passports: WE NEED TO GET OUR PASSPORTS NOW; in the U.S., it takes about 2 months to process for 1st time applications.
b. A meet-up is likened to a pilgrimage: What an emotionally healing experience previous meet-ups like this one have been in such a beautiful setting, as we experience a strong sense of ‘belonging’, as opposed to our usual sense of being an ‘outsider’ in our every day social experiences.

One of MeBO Research’s aims is to promote social awareness of systemic body odor amongst the scientific/medical communities, and in the public and political spheres.4. Raising social awareness: One of MeBO Research’s aims is to promote social awareness of systemic body odor amongst the scientific and medical communities, and in the public and political spheres. Some of the members of the call have expressed an interest in participating in political lobbying and media exposure under the MeBO umbrella as a non-profit organization.

5. Strive for independence in self-management of our odor: Like any other type of physically challenging condition, a sufferer needs to manage his/her condition in as independent manner as possible. In the case of a body odor condition, the sufferer need to be able to identify her specific type of body odor with a personal scientifically-based device that can detect and identify the primary volatile compounds causing the odor, to be able to correlate it with the specific triggers in the environment (foods, chemicals, etc), and thus, the sufferer can make better choices to manage her condition without having to ask anyone for help or having to ask others, “Do I smell?”

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Meet-up/Support group contacts

UK : Arun Nagrath: arunnagrath@hotmail.com
LA, California : Joel : joelm211@yahoo.com
Sacramento, CA: Kemetian: kemetian43@yahoo.com
Miami : Maria: mpdela1@gmail.com

Regular FREE (long distance call plan) General and Women-only Phone Conferences

General Conferences: normally every other Sunday at 2pm EST.
Next call : Sunday June 28th, at 2pm DST

Women's Conferences: normally every other Thursday 8.30pm EST. Next call: June 25th at 8:30p.m. DST

Arranged by the leaders of the bodyodorsupport.com forum

Note: can also be used anytime for unscheduled group chats

Free USA-based phone conferences (if you have a long distance call plan. Otherwise you will be charged as a long-distance call)

For USA-based : (712) 432 1620 then type the access code on your phone keypad: 391629#
Non USA : prefix above with 001 but check to see if it is free with your supplier


Record number of callers : 70+
If privacy is a concern, code your phone to PRIVATE mode
This phoneline can be used anytime to talk to other sufferers
You don't need to talk. You can just listen

Action plans

Write an essay on your odor problem for Richards anthology project
contact your Senator about blood-borne BO/halitosis
write to 'the Doctors' TV show
contact the DrHoffman show on WOR710
tell the Office of Rare Diseases about your problem
try the asparagus urine test
Fecal Body Odor Volunteer for media appearances ?
Politicians ?
Ask an expert if they will put up a Q&A section on their websites like Emory have

suggestions

Thinktank

Bluesky ideas to promote thought:

PTC124(Ataluren, or similar) for primary TMAU due to nonsense mutations
Genetically modified probiotics enriched with FMO3 ?
Trimethylamine strip test paper for daily urine testing? (possibly used in the fish industry ?)
BO&Halitosis research center
BO&Halisotis research fund
Can FMO enzyme be induced in a helpful manner ?
Ask an expert if they will put up a Q&A section on their websites like Emory have
BO&Halitosis 'rehab' retreat (?)
TMAU cookbook/advice book
Employ an expert to do the most thorough choline list
Employ Body odor/halitosis expert(s) (?)
Encourage breath-analysis manufacturers to make portable handy analyzers for metabolic odor problems
TMA urine dipstick test
Is trimethylamine an FMO3 inhibitor ?
Campaign : add TMAU to the newborn screening program

Send in your ideas or post them on the forums: Contact experts

Peer evidence for experts

>Christodoulou Trimethylaminuria research proposal April 2009
> 2008 dissertation: 8 out of 12 TMAU phenotypes had no known FMO3 mutation
> 3.8% fail the TMAU urine test. pubmed paper 1996
> smell of schizophrenia
Neonatal with encephalopathy and later a # pungent cabbage odor. H2S and methanethiol in urine. Makes full recovery. (Anecdotal paper:1997)
> Portal shunt in girl. TMAU reported as only symptom
> Number of trimethylamine cases in random international samples
> Dimethylglycinuria. 1st (and only ?) reported case
> Orphanet on TMAU: The prevalence is estimated to be approximately 1 %
> Analysis of VOCs from skin
> Human breath odors and their use in diagnosis
>
Results of Arun's Odor Survey

Books/Ebooks by warriors

Carry Wilson book/Ebook : The foul body odor that almost killed me
Alice Mata book/Ebook : When bathing is not enough

related papers


suggestions