Trimethylaminuria

What is trimethylaminuria?

Trimethylaminuria is also known as fishy (bad) odor syndrome'Due to the characteristic fishy body odor.

Trimethylamine is a volatile aliphatic. molecule, better known as the rotten fish smell. Marine fish are rich in trimethylamine N-oxide, which is converted to trimethylamine bacteria. Bacteria in the gut produce the smelly trimethylamine from trimethylamine N-oxide or choline. It is normally converted to odorless trimethylamine N-oxide by a enzyme in the liver, known as trimethylamine oxidase or flavin-containing mono-oxygenase 3 (FMO3). Humans are unusually sensitive to the odor of trimethylamine and can detect as low as 0.9ppm.

In trimethylaminuria, this malodorous molecule is excreted in sweat, urine, breath, saliva, vaginal secretions, and other bodily secretions. It is one of the causes of bromhidrosis (smelly sweat).

Who gets trimethylaminuria?

Primary trimethylaminuria is a rare autosomal recessive genetic disease (MIM 602079), which means that the affected person has inherited two copies of the defect gene, one from each parent. Two defective copies of the gene result in a failure to produce enough active FMO3 enzyme. Parents are generally unaware of carrying the gene, except in rare circumstances when they may temporarily develop body odor. 1% from the general population in the UK has been estimated to have a defective copy of the gene, ranging up to 11% in Papua New Guinea. The gene has been identified and many different mutations detected in patients. Some mutations cause a reduction in FMO3 enzyme activity and others result in a complete loss of enzyme activity. This form of trimethylaminuria usually presents in infancy after the child has been weaned on foods rich in choline or trimethylamine N-oxide. There is a female predominance in diagnosed cases and carriers.

Secondary trimethylaminuria occurs when the liver's FMO3 enzyme is overwhelmed or underactive for some reason. The enzyme can be overwhelmed by an excessive intake of trimethylamine precursors or when there is bacterial excessive growth in the intestine resulting in increased production of trimethylamine. The enzyme cannot cope with the increased level of trimethylamine absorbed from the intestine, and some of the trimethylamine leaks into the general circulation causing the characteristic odor. The enzyme may be not very active in liver and kidney disease, during menstruation or in the presence of inhibitors such as those derived from eating Brussels sprouts, oral thiourea or current hydroquinone In many cases, secondary trimethylaminuria is likely to occur in cases with an inherent reduction in enzyme activity, such as in a carrier for the defective gene (a heterozygote).

A transient form has been described in childhood. Investigations confirm elevated level of trimethylamine in urine, but actual conversion of trimethylamine to trimethylamine N-oxide is almost normal. It resolves spontaneously after months or years and the levels and conversion are normal. It is believed to be due to overproduction of trimethylamine in the intestine, although no abnormality could be demonstrated. It is important to distinguish this form from primary trimethylaminuria by measuring the levels of trimethylamine N-oxide and trimethylamine in the urine.

Trimethylamine is also the cause of the fishy odor associated with bacterial vaginosis.

Clinical features

The only characteristic of this condition is bad body odor (including halitosis, bad breath), of which the victim may be completely unaware. The victims are physically well with normal mental and general development.

Odor can fluctuate and triggers for an increase in odor include:

1. menstruation, with a worsening just before and during a menstrual period. Studies of normal subjects show reduced enzyme activity of 60-70% at this time. So it seems sex Hormones affect the ability to metabolize trimethylamine.
2. use of the oral contraceptive pill
3. excessive stress or emotional distress
4. exercise
5. infection, especially with fever
6. dietary intake of foods rich in choline or trimethylamine containing N-oxide.

However, this offensive body odor causes significant social problems that result in psychological distress and some develop an obsession with personal cleanliness. Children struggle in school with ridicule, rejection, and teasing about personal hygiene. Many severe cases drop out of school early because of this, resulting in educational disadvantage. In adult life, similar problems can occur in the workplace, affecting career prospects and causing difficulties with interpersonal relationships. This can lead to feelings of shame, shame, low self-esteem, and social isolation. Frustration, anxiety, depression, paranoia, drug addiction (cigarettes, alcohol, and illicit drugs), and attempted suicide are common outcomes, particularly for those severely affected. This is a condition with wide social and psychological effects.

How was the diagnosis made?

The diagnosis should be considered in patients presenting due to body odor, especially if it is described as suspicious. In a UK study of 187 patients who presented due to body odor, 17 were described as suspects. Eleven of the 17 had trimethylamine, but none of the others were affected by this condition.

The diagnosis is confirmed by a 24-hour urine collection on a normal diet and an 8-hour urine collection after a meal of marine fish (for children) or a 600 mg oral trimethylamine load (adults). Both trimethylamine and trimethylamine N-oxide must be measured. Trimethylamine challenge will detect both carriers and diseased, as both will have a reduced conversion to trimethylamine N-oxide. Normal subjects will convert more than 80% from trimethylamine to the N-oxide form, carriers convert less than 80%, and patients convert less than 25% after oral challenge. In menstruating women, the timing of the test is important as it can be a temporary problem.

The genetic mutation can be characterized, although this is generally for research purposes at present.

Treatment

Getting sick is a very important part of treatment as it recognizes your medical condition and explains the cause.

Diet modification is the basis of treatment, as avoiding trimethylamine precursors reduces body odor:

1. Marine fish (sea or saltwater), including cephalopods and crustaceans, should be avoided completely, as they have the highest concentration of the precursor N-oxide trimethylamine. You can eat freshwater fish.
2. Foods identified as high in choline include egg yolks, soybeans, peas, beans, peanuts and other legumes, liver, kidney and other offal, and brassicas such as rapeseed (canola). The choline in egg yolks may be in a form that gut bacteria do not convert to trimethylamine. Some people can eat foods in this category in reduced quantity.
3. The role of lecithins, carnitine, and other betaines remains unresolved. Red meat is rich in carnitine and some people may need to restrict its consumption.

Low wash pH (pH 5.5-6.5) soaps and shampoos remove traces of trimethylamine from the skin and hair.

Some patients respond well to courses of neomycin, amoxicillin, or metronidazole, as these alter intestinal bacteria, reducing the production of trimethylamine. This will be particularly useful in secondary trimethylaminuria due to bacterial overload and can be used in primary trimethylaminuria for important social situations or when dietary restriction cannot be maintained. To reduce the risk of antibiotic resistance, antibiotics should only be used intermittently or alternate every 2 weeks.

Oral copper-chlorophyllin may also temporarily improve by altering your gut bacteria.

In severe cases of primary trimethylaminuria, metabolism In theory, some of the drugs can be affected as they can be processed by the same FMO3 enzyme. Medications that may be affected include nicotine (in cigarettes), codeine, cimetidine, ketoconazole, sulindac, itopride, and tamoxifen. This can result in an exaggerated or increased clinical effect. incidence adverse drug events.

Hydroquinone used topically as a depigmenting agent has been reported to trigger fishy odor in those who use the drug in large amounts for a long time. As it is an antioxidant, it can inhibit the oxidation from trimethylamine N-oxide to trimethylamine, especially in carriers.