Loss-of-function mutations, nonsense mutations, and missense mutations are three of the most common. Nonsense and missense mutations cause the most severe phenotypes. Although FMO3 mutations account for most known cases of trimethylaminuria, some cases are caused by other factors. A fish-like body odor could result from an excess of certain proteins in the diet or from an increase in bacteria in the digestive system. A few cases of the disorder have been identified in adults with liver damage caused by hepatitis. In 2007 the evolution of the FMO3 gene was studied, including the evolution of some mutations associated with TMAU. Diagnosis
Measurement of urine for the ratio of trimethylamine to trimethylamine oxide is the standard screening test. A blood test is available to provide genetic analysis. The prominent enzyme responsible for TMA N-oxygenation is coded by the FMO3 gene. False positives can occur in the following conditions, where elevated TMA can be present in the urine without any underlying TMAU:

Urinary tract infection
Bacterial vaginosis
Cervical cancer
Advanced liver or kidney diseaseA similar foul-smelling odor of the urine has also been associated with colonization of the urinary tract with a bacterium called Aerococcus urinae, especially in children.Olfactory reference syndrome is a condition where there is a persistent false belief and preoccupation with the idea of emitting an abnormal body odor. According to McNiven at a canadian genetics clinic, 83% of referrals for genetic testing for TMAU were deemed likely to instead have ORS.
Polyphosphoric acid (PPA) cyclization leads to 5-fluoro-2-methyl-3-indanone (4). A Reformatsky reaction with zinc amalgam and bromoacetic ester leads to carbinol (5), which is then dehydrated with tosic acid to indene 6. {Alternatively, this step can be performed in a Knoevenagel condensation with cyanoacetic acid, which is then further decarboxylated.} The active methylene group is condensed with p-methylthiobenzaldehyde, using sodium methoxide as catalyst, and then saponified to give Z (7) which in turn oxidized with sodium metaperiodate to sulfoxide 8, the antiinflammatory agent sulindac. References
External links
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