Trimethylaminuria

background

Trimethylaminuria (TMAU) is an inherited metabolic disorder that is characterized by an offensive body odor that smells like rotting fish. This odor is due to the excessive excretion of a protein called trimethylamine (TMA) in the urine, sweat, and breath.
TMAU, also known as fish odor syndrome or fish malodor syndrome, is caused by defects in a protein called flavin-containing monooxygenase 3 (FMO3). The FMO3 protein is an enzyme produced by the liver that functions mainly to break down nitrogen-containing compounds.
TMA is consumed through the diet and is normally broken down through a process called N-oxygenation. The abnormal function of FMO3 results in the body's inability to break down TMA from food sources, especially choline-rich foods, such as milk, eggs, and peanuts. When this process does not work properly, TMA builds up and is released in the person's sweat, urine, and breath. This causes the characteristic smell associated with TMAU.
Trimethylaminuria is a rare genetic condition with unknown incidence. This inherited disorder demonstrates how genetics can alter the way dietary substances are broken down (metabolized). However, TMAU has been diagnosed in people who have liver disease but do not have a family history of the disorder.
While TMAU does not cause other medical problems, it can be extremely stressful for affected individuals. While some people with TMAU are not aware of their body odor, other people with the condition are very sensitive to it and may become socially withdrawn as a result. The disorder can cause generally negative effects on educational, personal, social, and career environments. TMAU has also been associated with severe depression, occasionally leading to suicidal tendencies, although evidence of this is lacking.
While no cure exists, treatment focuses on reducing the odor release, most often through dietary restriction of foods containing choline, nitrogen, and sulfur. People with TMAU are otherwise healthy.

Related Terms

Acquired trimethylaminuria, fish malodor syndrome, fish odor syndrome, flavin, FMO3, metabolic disorder, precursor overload trimethylaminuria, primary genetic trimethylaminuria, stale fish syndrome, TMAU, TMAuria, transient childhood trimethylaminuria, transient menstrual trimethylaminuria, trimethylamine.

types of the disease

Primary genetic form: The primary genetic form of trimethylaminuria (TMAU) is the best understood and most commonly occurring type of this disorder. Research on this form of TMAU has clarified the role of the flavin monooxygenase group of enzymes in breaking down trimethylamine (TMA) in the body. The gene that codes for flavin monooxygenase 3 (FMO3) has been the most closely related to TMA metabolism, and therefore warrants further research into different types of mutations that can occur. Some mutations of the FMO3 gene have been associated with dysfunctional enzyme activity similar to what has been observed in TMAU. Two mutations have been identified as occurring more commonly than others in patients with the primary genetic form of TMAU, and these account for most severe cases.
While researchers believe that most cases of TMAU are caused by genetic mutations that stop the activity of the FMO3 enzyme, more research is necessary to determine whether certain mutations are combined with others to cause a less severe form of TMAU.
Acquired form: Several cases of TMAU have been observed in which individuals developed the disorder during their adult lives. These patients had no childhood incidence or family history of TMAU. Evidence of hepatitis, or inflammation of the liver, was common to all of these adult cases. Researchers hypothesized that in these cases, damage to the liver caused permanent changes in the activity of the FMO3 enzyme.
Transient childhood form: Temporary fish-like body odor associated with TMAU has been observed in infants being given a choline supplement. This type of TMAU may have been the result of the immaturity of the enzyme needed to break down TMA and is not believed to be inherited. Varying degrees of this type of TMAU have been observed throughout childhood in several cases of the disorder.
Transient form associated with menstruation: Studies have shown that in normal healthy women, a short episode of TMAU may occur at the onset of and during menstruation. This type of TMAU is generally regarded as the result of hormone changes, is usually temporary, and is not considered to be genetically inherited.
Precursor overload: A few cases of temporary TMAU have been observed in people who have been exposed to unusually high levels of TMA precursors, or compounds that eventually form TMA. This is most likely to occur in people who are carriers of the FMO3 mutation or anyone taking large oral doses of choline, which is sometimes used to treat Huntington's chorea. It should be noted that the precursors of TMA, including choline and lecithin, are sometimes found in health foods, supplements, and alternative diets. Therefore, certain diets may cause temporary symptoms of TMAU.