Trimethylaminuria )

  1. Missing user
    about 5 years ago
    Chronic and difficult to control, if not impossible to control, body odor and halitosis are the result of a physical impairment that causes social isolation with significant adverse implications on quality of life, productivity and psychological health. It is a universal disease, which transcends national and racial boundaries, as depicted by sufferers coming together from around the world under MEBO’s flagship to proactively pursue research for treatment and a cure.

    All human interaction experienced by body odor and halitosis sufferers is compromised at a most basic level, whether it is in the workplace, education, general public or indeed romantic and family life, leading to discrimination transcending the home, workplace and in the general public. Offensive odor as a stimulus for the uninitiated creates a strong aversion, an evolutionary response to potentially infectious stimuli. The evolutionary response to noxious olfactory stimuli is one of disgust. It is possible that the impact of these conditions on patients’ lives is great. Social relationships are one of the pillars of quality of life, and social isolation is known to correlate with psychological comorbidities, such as chronic depression and anxiety. Patients with difficult to control body odor and halitosis frequently tell a sorry tale of constant social rejection, psychosocial assaults, and as a result, usually have lives of isolation with all the associated psychological comorbidity that this entails.

    Barriers to obtaining employment at interview:
    There are likely to be discriminative and human rights issues if this malodorous medical condition is present, no matter what the qualifications, personality traits, personal appearance and demeanor of a job candidate. Few employers would be willing to recruit a malodorous person to a workforce. The repeated rejections are not usually openly discussed, as employers are quite careful not to incite discrimination suits against themselves.

    Workplace discrimination:
    Those body odor and halitosis patients who manage to find employment are prone to face further discrimination and develop a deep sense of job insecurity and instability, which further contributes to chronic depression and the development of an anxiety disorder. As mentioned previously, malodor medical conditions are virtually unknown by members of the general public. The workplace becomes just another platform of compromised social interaction. There are frequent reports of unfair dismissal, sustained bullying campaigns and other inequalities such as being overlooked for promotion, etc.

    Social anxiety and depression preventing work:
    It is unnatural and unhealthy for an individual to exist in a state of constant social rejection. Such maltreatment all too frequently comes at a psychological cost to the patient. Social anxiety and depression are especially prevalent, and these are well known issues related to decreased productivity and unemployment.

    Cost of medical and dietary management:
    It will by now be readily apparent that even if the symptoms of body odor and halitosis can be controlled (not always possible for many patients), its management can become a lifestyle, demanding constant attention and research. If the patient manages to find employment that provides medical insurance benefits, few medical insurance policies cover conditions like TMAU, resulting in tremendous financial cost to the patient.
    The rareness of the conditions can mean that patients must travel long distances to specialist physicians for consultation and treatment. This is costly not just financially, but in terms of time costs, which could make work difficult for sufferers.
    Dietary supplements, specialist foods, soaps and antibiotics and the other products that aim to control the symptoms do not come cheap, and nonetheless, are limited in its effectiveness in controlling symptoms.

    Barriers to higher education and other qualifications:
    Since body odor and halitosis symptoms present at an early age, education is adversely affected, leading to restricted employment opportunities throughout the person’s potentially productive years. As such, It is a condition comprising of anxiety, depression, social maltreatment, bullying in the schools, and general discrimination, which leads the sufferer toward a reclusive life of isolation. This is particularly most damaging during the developmental stage in one’s life, in puberty, when the odor most typically worsens with hormonal changes. It is during this time, that a sufferer is bullied in school, compromising his or her normal psychosocial and psychosexual development. In addition, since hormonal changes trigger more severe odor symptoms just before and during menstruation, females are particularly compromised in their psychosocial and psychosexual development. As a result, many sufferers drop out of school.
  2. Missing user
    about 5 years ago
    I would like to see a mouse model that present all the FMO3 mutations related to TMAU. Not all FMO3 mutations cause TMAU, but only some. I have this data, and I will post it bellow. In addition, to the mouse model, I would like to see a researcher who creates the proper corrections of the mutations, using genome editing tools -like CRISPR Cas9. I believe this research is quite attainable with a small amount of funds.
    This step forward will put us ahead and, will allow us to move to phase two.
    Here is the data FMO3 mutations related to TMAU -please scroll to the right to see if the mutation causes TMAU: http://databases.lovd.nl/shared/transcripts/01793

    The next phase is to collaborate with researchers who are currently doing liver regeneration using stem cells. There are a few ( I will post the links). The idea is to take the cells -which ever they use, convert them into stem cells, correct the mutations (as done previously -read above), then convert them into liver cells, and finally, transplant them back into the patient. Here are the links to the researchers who have recently achieved Liver maturation using stem cells:



    Another collaboration idea, is to remove the liver, then hook the body up to an artificial liver -I will post the link bellow. The liver is then hooked up to a device called 'lung in a box:' a device that is used to mimic the role of the lungs in heart transplantation. The liver is therefore is preserved. Mutations are corrected using CRISPR, and the fixed liver is transplanted back into the patient. The researcher who is creating the artificial liver is the one to collaborate with. Here is the link:

    Ultimately, I don't think these liver researchers have the time and money to research TMAU. Therefore creating the mouse models before hand would put us ahead. Then it is a matter of taking their research, which is to auto-transplant the liver, and adding the research done to make the corrections to cure TMAU -type 1.

    I don't believe enzyme therapy is attainable. It is far too expensive. I believe there is one disorder that uses enzyme therapy and it costs $400, 000 a year/per person. In addition, it is done through injections at the hospital. First of all, there is no insurance to cover this condition, so that is out of the question. Secondly, the injections would have to be done through the liver. It's simply aiming for something that will not work.
  3. Missing user
    about 5 years ago
    I have been waiting a long time for a platform such as RE(ACT) due to it's ability to release money available among sufferers (and the public) to help the cause. Here are some of my overall thoughts on TMAU

    My own view of 'TMAU' is that sufferers may have problems oxidizing all FMO3 substrates, and may actually smell of any FMO3 substrate, which seem to be mostly small sulfides and amines. So I would call it something like 'FMO3 substrate malodor'/ 'FMO3 malodor' / FMO3 malodor syndrome'/ sulfide and amine (as a generalisation) malodor.

    Perhaps trimethylamine is a 'baseline/signature' malodor for FMO3 cases, perhaps moreso in 'severe' cases. It should be an excellent biomarker of FMO3 function but for some reason I don't think this is always the case. Malodor sufferers are usually told to only do the urine test, but I would suggest the DNA test too (full sequencing (with a copy of all the 532 codons given). At the moment most of this subject is unknown, whereas the default attitude of the medical system is that everything is known. So this problem is still at an exploratory stage.

    However, since I think TMA is definitely one metabolite that someone with FMO3 issues will have, I am currently happy to go along with the notion that TMA is the only volatile that will be an issue.

    Re RE(ACT), I think as well as major research projects, there is also the opportunity of small inexpensive research studies. Here are some of my ideas of study projects which may/may not be sensible :

    Major studies :
    Cure : enzyme replacement therapy, gene therapy etc

    Small inexpensive studies :
    1. e.g. Studies where sufferers will pay for their own testing

    2. e.g. Test choline levels in people diagnosed with TMAU, both before and after 'treatment' (my suspicion is that TMAU sufferers may be naturally deficient due to bacteria altering choline in the gut)

    3. Test B vitamin status of sufferers, since it may be underestimated how much of B vitamins is generated by a healthy gut flora

    4. Broad spectrum volatile urine test : Rather than limiting malodor testing to TMA, do a broad spectrum test of volatiles in sufferers. Once the main offending volatiles were noticed, this would become the main test for FMO3 sufferers

    5. Database of all TMAU/FMO3 test results

    6. Body odor and halitosis Research Center and Clinic

    These are just some of my thoughts on the subject.