Триметиламинурия: Синдром запаха рыбы

Trimethylaminuria (TMAU), also known as fish odor syndrome or fish malodor syndrome, is a rare metabolic disorder that causes a defect in the normal production of an enzyme named flavin containing monooxygenase 3 (FMO3). When FMO3 is not working correctly or if not enough enzyme is produced, the body loses the ability to properly convert the fishy smelling chemical trimethylamine (TMA) from precursor compounds in food digestion into trimethylamine oxide (TMAO), through a process called N oxidation. Trimethylamine then builds up and is released in the person's sweat, urine, and breath, giving off a fishy odor. Primary trimethylaminuria is caused by genetic mutations that affect the FMO3 function of the liver. Symptoms matching TMAU can also occur when there is no genetic cause, yet excessive TMA is excreted this has been described as secondary trimethylaminuria (TMAU2).

Trimethylamine is most noticeable in urine, as it is captured, concentrated and released in intervals. Fishy smelling urine is a primary identifying symptom in infant children (Trimethylaminuria literally meaning "trimethylamine in urine"). Trimethylamine is also released in the person's sweat, reproductive fluids, and breath, and can give off a fishy odor when the concentration of trimethylamine is high enough to be detected. The intensity of the smell is directly correlated with the concentration of trimethylamine in the bloodstream. People with TMAU may have an intermittent fish like body odor, depending on diet and the severity of their FM03 mutation. In a study by Wise PM, of 115 positively identified TMAU subjects, after a choline challenge load test (intentionally ingesting a TMA precursor) only 10% expressed a smell at a social distance. When in a fasted state (12 hours) 0% had a smell detectable at a social distance and only 5% had some minor malodour at an intimate distance. These findings suggested that those that produced an odour had a more severe form of FMO3 impairment. Smell events are often sporadic and episodic in nature (based on diet over the previous 24 hours), making it often difficult to diagnose by smell alone. Some people with trimethylaminuria report having a strong odor all the time, but there has not been any evidence apart from self reported symptoms that this is the case. Individuals with this condition do not have any physical symptoms, and they typically appear healthy. The condition seems to be more common in women than men, for unknown reasons. Scientists suspect that such female sex hormones as progesterone and estrogen aggravate the condition. According to several reports, the condition worsens around puberty. In women, symptoms may worsen just before and during menstrual periods, after taking oral contraceptives, and around menopause. Loss of function mutations, nonsense mutations, and missense mutations are three of the most common. Nonsense and missense mutations cause the most severe phenotypes. In 2007 the evolution of the FMO3 gene was studied, including the evolution of some mutations associated with TMAU.

Although FMO3 mutations account for most known cases of trimethylaminuria, some cases are caused by other factors. A fish like body odor can result from extreme excess consumption of TMA precursors such as choline, carnitine and betaine (usually unobtainable via regular dietary intake, it requires high levels of supplement intake). 900mg of trimethylamine, 8g 20g of choline, 3g of carnitine or 20g betatine has been known to cause temporary TMAU like fish odour symptoms. These symptoms only last until supplement intake has ceased. Note, the RDI for choline is 450 550mg and most typical diets fall below this value, so an excessive amount of precursor is required. Two cases of the disorder have been identified in adults with liver damage caused by hepatitis. It is unknown if these cases were temporary or not as the individuals did not return for subsequent testing. There is no reference to scientific research confirming gut dysbiosis alone can cause TMAU2, and this type of diagnosis was not produced at other testing sites. Cases were claimed to be successfully cured with antibiotics and dietary changes as above. In 2017 a new gas chromatography machine and testing procedure was introduced, which has far fewer false positive results, and very few (if any) TMAU2 results. While the balance of gut bacteria does play a part in the amount of TMA being produced from precursors in the gut (antibiotic treatment temporarily stops odour), gut bacteria in general convert a significant proportion of dietary TMA precursors already. For example, on average 63% of excess choline, and 31% of carnitine (+ 13%) are converted to TMA Her mother related that her child, a 6 year old girl, had intermittently had a peculiar "fishy" odour. Analysis of her urine showed an elevated level of trimethylamine, and that a chemically pure free base sample of trimethylamine smelled similar to the patient's fishy odor. They tested her condition by giving her more trimethylamine, which substantially increased her odour (which it did not in control subjects).

In 2014, singer/songwriter Cassie Graves was first featured in the Daily Mail, the Daily Mirror, and The Metro UK newspapers in both print and Online, giving an interview about her experiences with Trimethylaminuria. The article was later repurposed in media across the globe, most notably by HuffPost. In 2016, Graves was then featured in Princess Productions' Medical Mysteries on UK's Channel 5, which went on a journey to find an official diagnosis for the condition, and again sparked a global media interest in the condition. The 2010 novel Boxer, Beetle by Ned Beauman features a character with trimethylaminuria. The 2023 film The Holdovers, directed by Alexander Payne, features a character with trimethylaminuria, although the condition was first described in the year in which the movie takes place.