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 trimethylaminuriaPubmed search : Shephard EAProfessor EA Shephard UCL page Pubmed search : Phillips IR
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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
related links:
more about FMO3 on NIH page
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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 Park
The 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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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.
http://www.tmau.org.uk/It also has a
TMAU forumIt's good to see so many metabolic body odor websites now making an appearance on the internet
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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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New: the people's 
Write an essay, poem or short story on your odor problem for Richards 
