About Trimethylaminuria

Trimethylaminuria (TMAU) is given its own page since it is currently the only accepted 'systemic' body odor condition by the medical community. It was detected in 1970 by a group of doctors in Colorado who tested a child with other health issues. The child was also said to have a 'fishy odor' at times. They performed a urine test and discovered high levels of trimethylamine (TMA). The Colorado lab today is still perhaps the only clinical lab in the USA with any long-term interest in TMAU. HBRI also has an interest in the FMO3 genetics.

Primary Trimethylaminuria is a genetic metabolic disorder inherited in an autosomal recessive manner.  The parents of an affected individual are obligate heterozygotes and therefore, carry one mutant allele.  Heterozygotes (carriers) are asymptomatic.  TMAU is determined by DNA mutation analysis of the FMO3 gene indicating a deficiency in the FMO3 metabolic enzyme produced in the liver.  TMAU is an autosomal recessive condition, meaning that each parent of the individual is carrier of one mutant allele whether they are asymptomatic or not, though mild or intermittent symptoms can sometimes occur in carriers of FMO3 mutations.  This deficiency of FMO3 enzyme results in an inefficient FMO3 function with a failure to process the chemical Trimethylamine(TMA), which can often smell of rotting fish, as well as other compounds that contain nitrogen, sulfur or phosphorous.  Symptoms are usually present from birth and may worsen during puberty. In females, symptoms are more severe just before and during menstruation, after taking oral contraceptives, and around the time of menopause. It is generally regarded that there are 2 types of Primary TMAU : the severe type, and mild type. The severe type is the textbook type of TMAU, where the person has 2 mutant copies of FMO3 and is very low-functioning. It is now accepted that milder forms exist, and these will usually involve variants or polymorph FMO3 copies, which are usually much more higher functioning but below normal. The current estimate of severe TMAU is not greater than around 1 in 5000, which in the USA could mean a 'severe TMAU' estimate of around 60,000. Presumably the number of 'mild' cases would be much higher. Primary trimethylaminuria can be generally assumed to mean 'FMO3 deficiency', although there are cases where FMO3 variants can metabolize certain types of FMO3 substrates but not others. in the TMAU urine test, the main part to do with Primary TMAu is the level of trimethylamine-oxide (TMAO).

Trimethylaminuria is a chemical created in the intestines by a few bacteria in the colon during the digestive process of foods containing choline and TMA.  It is normally transported to the liver to be broken down into non-odorous Trimethylamine-n-oxide (TMAO) by the flavin-containing monooxygenase 3 (FMO3) metabolic enzyme produced in the liver.  Both TMAO and TMA are normally excreted in the urine.  However, when there is a deficiency of the FMO3 enzyme due to an autosomal recessive condition resulting in an FMO3 mutation, TMA is then not oxidized, and thus remains in an odorous state.  Over time, this chemical compound may stay in the body longer building up and causing the excretion of a strong and offensive odor to leave the body through every single pore, breath, urine, and reproductive fluids.    

Secondary Trimethylaminura (TMAU2) is an acquired form of TMAU involving an overproduction of TMA by gut flora in a patient with normal FMO3. Experts believe that TMAU2 from overproduction of TMA by bacterial overgrowth can be experienced for many years but if the correct antibiotic therapy is applied, can be cured by eradication of the bacteria responsible. Secondary TMAU or TMAU2 has been recognized for many years, especially in the UK, although much of the TMAU interest has been in the inherited metabolic disorder FMO3 deficiency, i.e., TMAU1. Both TMAU1 and TMAU2 can be controlled with periodic antibiotic therapy as well as dietary choline restriction of eggs, liver, beans, carnitine (meat), and TMA-oxide (seafood). The odor effects of TMA may also be reduced by activated charcoal or copper chlorophyllin tablets to adsorb TMA in the gut and the use of pH5 skin creams to neutralize TMA in sweat.

Psycho-social consequeces : This offensive odor significantly interferes in the sufferer's social life, such as in school, work, or personal relationship.  This social crisis usually results in profound psycho-social side effects, as portrayed in our community Anthology, 'Conquering the invisible monster' written by sufferers as a fund-raising tool for MeBO Research. As a result of this condition, sufferers fall into a deep depression and intense state of anxiety, become recluse, and develops a very lonely lifestyle without relief in sight.   One of the most traumatic aspects of this disorder is that the sufferer has no recourse in the medical system to find treatment and a cure, and finds it difficult to understand why the medical community is not well versed in this condition.  Therefore, a sufferer very rarely receives the necessary appropriate medical attention and treatment to control the odor.