In this age of modern medicine, most individuals would assume that all ‘obvious’ health problems have been characterized and diagnosis and treatment regimens developed. However, it may be a surprise to some pediatricians that perhaps at least one ‘obvious’ health problem remains right under their noses and underappreciated: systemic body odor, including a form wherein individuals can smell of a broad spectrum of bowel-related odors, including fecal- and gas-like smells. Before the internet, most sufferers thought they were the only ones with such strange body odor, but with the maturing of the internet and development of online communities, it is clear that systemic body odor could be a far more common problem than first thought. The typical pattern is despite good hygiene the odor persists because it is being produced internally. Typical cases seem to start at a young age, especially around puberty and the mid teens. Most cases are probably ‘transient’; making presentation of the symptoms to a doctor difficult. Many cases also are almost undetectable to the person and to their family, perhaps due to desensitization, which makes monitoring the condition extremely difficult. A wide range of ‘bowel’ smells have been described (generally based on social accusations), including fecal, gas, rotten eggs, sewage, garbage, rotten fish, or burning rubber.
The first obvious cause would be genetic. However there seems to be a size-able number of individuals who develop the problem in their 20’s, 30’s, or even older; suggesting there may be an environmental factor involved. Individuals also may exhibit adverse reactions to certain medications and herbs, perhaps indicating an issue with one or more of the drug-metabolizing enzymes.
Although it may seem a trivial disorder when compared to other metabolic disorders, the psychological impact cannot be underestimated. Individuals suffering from this problem end up are ostracized from society, exacerbated by the fact they cannot detect the problem themselves and so cannot monitor their condition. Suicide rates likely are very high due to depression and anxieity. Some have expressed an opinion that the problem arises in the form of halitosis rather than body odor. However, because most sufferers cannot detect the odor themselves, it may be hard for them to know what their own odor problem actually is.
Currently, the only generally accepted form of ‘systemic body odor’ is trimethylaminuria, which was first diagnosed around 1970, although the condition was actually described in the Indian epic,
, and in Shakespeare’s
. The genetic form of TMAU is due to deficiencies in flavin-containing monooxygenase 3 (FMO3), an enzyme which can oxidize a wide range of substrates, including nitrogen, sulfur containing compounds. Trimethylamine in humans is thought to come mainly from bacterial degradation of dietary choline and the breakdown of trimethylamine N-oxide from seafoods (not freshwater fish). Despite being known for over 40 years, a minimal amount of research has been devoted to the disease, and it is not covered by the disability act, leading to individuals being caught between humiliation at work or destitution.
One major question is whether TMAU completely explains the majority of cases of ‘benign’ systemic body odor, given that very few complain of being told they smell of fish. Most are told they smell of feces, gas, bowel smells etc. Although many sufferers are proven to have TMAU based on a positive phenotype test result, there does seem to be anomalies, with quite a few such individuals subsequently being ‘negative’ for the genotype test. One theory is that it may in fact be mostly ‘body odor due to FMO3 deficiency’, with gut dysbiosis also playing a role in pushing the person over their saturation point. However, previously undescribed FMO3 mutations also may contribute. Perhaps ‘fish odor’ is a baseline marker. Another question unanswered is how common is TMAU? Carriers have been estimated to be present in the British population at 1% frequency, but in areas of Australia, Ecuador, and New Guinea, carrier frequencies as high as 3 to 11% have been reported. Another question is why parents cannot usually smell their child who suffers from this disorder? One theory is that perhaps ‘carriers’ are desensitized to the smell. (If you think of anyone with any type of body odor or halitosis, the question is, why doesn’t a loved one tell them?) Also, most TMAU positive cases are ‘mild’.Given that the gut flora may slowly change with age, there also may be the chance of such changes increasing risk for the disorder. To complicate matters further, FMO3 is not easily inhibited or increased, unlike many other drug metabolizing enzymes. However, indoles have been shown to inhibit the enzyme.Some females also exhibit TMAU symptoms at the onset of menstruation. Finally, sufferers often report that ‘strong emotions’ can instantly induce their odor problem, perhaps due to increased sweating.
Another issue is the number of labs clinically testing for TMAU and no standardized range that is clearly linked to the disease. As such, each lab sets their own range. Currently there are only 3 known clinical TMAU phenotype testers known in the USA: in Arkansas, Denver and San Diego. One lab only tests for TMA and not TMAO and it is not possible to gauge FMO3 function via TMA levels alone.
Another published form of systemic body odor is dimethylglycinuria, from a 1999 case. However no other cases have been reported, despite occasionally being clinically tested for. Possibly there is a need for a broad range of malodorous human VOCs to be tested for in cases of systemic body odor that would provide clues to other causes. Another possibility for systemic body odors is that the person is a carrier of a very serious metabolic disorder already known to cause a smell, such as isovaleric acidemia. At the moment they are regarded as being ‘asymptomatic’, however perhaps a transient odor problem is possible. In most cases on the forums though, the main form seems to be what they call ‘fecal body odor’, which would seem to indicate the drug-metabolizing enzymes in particular, given the wide range of smells involved. The problem of systemic body odor needs urgent attention, to stop people living meaningless lives.
Some ideas for research have been the founding of a body odor and halitosis research center and clinic, which could include all forms of these conditions including apocrine body odor. There are already a few ‘taste & Smell’ clinics in the USA, but not for odor conditions. Other ideas are handheld or wrist ‘odor’ sensors to monitor the condition, special diets, future treatments for whatever enzyme is responsible, add TMAU to the newborn screening program, add TMAU testing to the pediatric unit, etc etc.
At this stage, discovering all the forms of systemic body odor is a priority, so that treatment and reseach can follow. Thank you for reading.
General Reference links on TMAU :
Gene Reviews TMAU article
Genetics Home Reference TMAU article Gene Reviews TMAU article
Trimethylaminuria: The Fish Malodor Syndrome
Eugène M. Trimethylaminuria; Orphanet encyclopedia, August 2002
2006 paper : Diagnosis and management of trimethylaminuria (FMO3 deficiency) in children
Trimethylaminuria and a human FMO3 mutation database
Dr Eileen Treacy overview of TMAU for OMMBID
Sheffield Children’s Hospital TMAU phenotype testing overview and procedure (pdf document)
1991 paper : The identification of trimethylamine excess in man: quantitative analysis and biochemical origins
Interesting TMAU case studies :
2006 case study : trimethylaminuria in an adolescent
2007 paper : Human breath odors and their use in diagnosis
1970 case study : First reported case of TMAU
2003 paper : TMAU related to the choline concentration of infant formula
FMO3 Reference:
2005 paper : Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism
2006 paper : Mutation, polymorphism and perspectives for the future of human flavin-containing monooxygenase 3
2008 paper : Flavin mono-oxygenase (FMO)--the 'other' oxidase
Links alluding to commonality of those at risk of TMAU due to FMO3 enzyme deficiency:
2008 dissertation case study : 8/12 positive for TMAU phenotype test did not show any mutants in DNA test
2007 case study : Transient trimethylaminuria related to menstruation
1999 paper : Mild trimethylaminuria caused by common variants in FMO3 gene
1999 Dr SC Mitchell letter to lancet : Trimethylaminuria: susceptibility of heterozygotes
2001 paper : In vivo variability of TMA oxidation is partially mediated by polymorphisms of the FMO3 gene
2000 paper : Biochemical and molecular studies in mild flavin monooxygenase 3 deficiency
1996 case study : 3.8% of 421 random volunteers are <90% in TMAU urine test
1997 case study : 11 of 100 random New Guineans are <80% in TMAU urine test
2000 : A Kashyap and S. Kashyap letter to lancet
Other possible issues with FMO3 deficiency
2000 paper : Population-Specific Polymorphisms of the HumanFMO3 Gene: Significance for Detoxication
1997 case report : TMAU associated with seizures and behavioural disturbance
2007 paper : Genetic polymorphisms of human flavin-containing monooxygenase 3
2002 paper : Human flavin-containing monooxygenase (form 3): polymorphisms and variations in chemical metabolism
Possible Fecal Body Odor cases ?
1973 case report : possible FBO case. Systemic cause not regarded
1997 : neonate with a pungent odor
5 comments:
I thought that the article was very informative and thought provoking; especially for me given that I suffer from what I can now call systemic body odor-typical smells are fish-like and fecal as reported to me by others. Of course I can't smell these odors nor can some of my friends and family members. I am fully aware of the psychosocical ramifications. Relatives don't want to hug me, while strangers stand far away in check out lines. I am afraid to seek employment. At my last job I was ridiculed and accused of not bathing. It is good to know that MEBO exist and I would like to become more involved in this effort. I am very interested in current treatment modalities and ways to tell others that this is a biophysiological malady.
My apologies for getting back late. I seemed to have missed your reply due to a technical hitch. I will reply more in-depth later.
A loads of people just are too embarressed to tell doctor about their problem, so the people count suffering from TMAU could be a lot bigger.
I agree. I reckon it could be 1% 'at risk'. maybe even 2%.
I have a mainly faecal odour mainly through breath I think my nose it changes from sewage to egg to and another smell I can't figure out I think it also come out of my pores I can smell myself outside but not inside for some strange reason it started at 13 but I hit puberty at 11 with no odour it is severe when it is bad people can smell me from 30ft away but my sweat smells normal I have had this for 7 years now I am so confused and depressed is an understatement any advice will be helpful.
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