Trimetilaminuria ( TMAU ; primary trimethylamamuria ), also known as fish odor syndrome or malodor fish syndrome , is a rare metabolic disorder that causes defects in the normal production of an enzyme called monooxygenase 3 containing flavin ( FMO3 ). When FMO3 is not working properly or if insufficient enzyme is produced, the body loses the ability to alter trimethylamine (TMA) correctly from the precursor compound in the digestion of food to trimethylamine oxide (TMAO), through a process called < i> N -oxidation. Trimethylamine then builds and is released in the sweat, urine, and breath of a person, giving a strong fishy odor or strong body odor. TMAU variants ( secondary trimethylaminuria or TMAU2) exist where there is no genetic cause, but excessive TMA is secreted, possibly due to intestinal dysbiosis, altered metabolism, or hormonal causes.
Video Trimethylaminuria
Symptoms
Trimethylamine accumulates in the patient's body with trimethylaminuria. Trimethylamine is released in sweat, urine, reproductive fluid, and the breath of a person, providing a stench or strong body odor. Some people with trimethylaminuria have a strong odor all the time, but most have a mild smell that varies in intensity over time. Individuals with this condition have no physical symptoms, and they usually seem healthy.
This condition seems to be more common in women than men, for unknown reasons. Scientists suspect that female sex hormones such as progesterone and estrogen exacerbate the condition. According to some reports, the condition worsens around puberty. In women, symptoms may worsen before and during the menstrual period, after using oral contraceptives, and around menopause.
Odor appears to vary depending on many known factors, including diet, hormonal changes, stress levels, sweat quantity, other odors in space, and the observer's sense of smell.
Maps Trimethylaminuria
Genetics
Most cases of trimethylaminuria appear to be inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Parents of an individual with an autosomal recessive disorder are both carriers of one copy of the altered gene. The operator may have mild trimethylaminuria symptoms or experience episodes while body odors such as fish.
Mutations in the FMO3 gene, found on the long arm of chromosome 1, cause trimethylamuria. Genes FMO3 create enzymes that break down nitrogen-containing compounds from the diet, including trimethylamine. These compounds are produced by bacteria in the gut when they digest proteins from eggs, meat, soybeans, and other foods. Typically, the enzyme FMO3 converts trimethylamine smelling fish into trimethylamine N -the odorless oxide. If the enzyme is lost or its activity decreases due to mutations in the FMO3 genes, trimethylamine does not break down and instead accumulates in the body. Because the compound is released in the sweat, urine, and breath of a person, it causes a strong characteristic trimethylamuria odor. Researchers believe that stress and diet also play a role in triggering symptoms.
There are more than 40 mutations known to be associated with TMAU. The loss of functional mutations, nonsense mutations, and missense mutations are the three most common. Nonsense and missense mutations cause the most severe phenotype.
Although the FMO3 mutations occur in the most known cases of trimethylamuria, some cases are caused by other factors. Body odor such as fish can occur due to excess of certain proteins in the diet or from increased bacteria in the digestive system. Several cases of disorders have been identified in adults with liver damage caused by hepatitis.
In 2007 the evolution of gene FMO3 was studied, including the evolution of several mutations associated with TMAU.
Diagnosis
The measurement of urine for the trimethylamine ratio for trimethylamine oxide is a standard screening test. Blood tests are available to provide genetic analysis. The leading enzyme responsible for TMA N-oxygenation is encoded by the FMO3 gene .
False positives can occur under the following conditions, where high TMA can be present in the urine without the underlying TMAU:
- Urinary tract infection
- Bacterial vaginosis
- Cervical cancer
- Advanced liver or kidney disease
The smell of a similar urine has also been linked to urinary tract colonization with a bacterium called Aerococcus urinae , especially in children.
Treatment
There is no known cure or treatment for this disorder.
The metabolic and clinical manifestations of TMAU are generally regarded as benign, since there is no associated organ dysfunction. This appointment, and the fact that this condition is often not recognized by a doctor, can have important consequences including a missed or delayed diagnosis.
Affected individuals experience shame and embarrassment, failing to maintain relationships, avoid contact with people who comment on their condition, and obsessive about covering up odors with hygiene and even smoking products. The foul-smelling aspect can have serious and damaging effects on school, personal life, career and relationships, resulting in social isolation, low self-esteem, depression, paranoid behavior, and suicide. Delayed diagnosis, body odor and lack of healing can cause psychosocial problems. When a condition is suspected or known to occur within the family, genetic testing may be helpful in identifying specific individuals who have or carry the disorder.
How to reduce the stench can include:
- Avoid foods such as egg yolk, beans, red meat, fish, beans and other foods containing choline, carnitine, nitrogen, sulfur and lecithin
- Take low-dose antibiotics such as neomycin and metronidazole to reduce the amount of bacteria in the intestine
- Use a slightly acidic detergent with a pH between 5.5 and 6.5
In addition, at least one study has suggested that the daily intake of activated charcoal supplements and copper chlorophylin can improve the quality of life of individuals suffering from TMAU by helping their bodies to oxidize and turn TMA into odorless N-oxide (TMAO ) metabolites. Study participants had subjective reductions in odors as well as objective reduction in TMA and increased TMAO concentrations measured in their urine. The study found that:
- 85% of the test takers experience a total "fishy" smell that can be detected
- 10% decrease in detectable odors
- 5% did not experience a detectable odor reduction
History
The first clinical case of TMAU was described in 1970.
References
External links
This article combines public domain text from the National Drug Library and the National Human Genome Research Institute
Source of the article : Wikipedia
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