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Trimethylaminuria


Other Names for this Disease

  • Fish malodor syndrome
  • Fish odor syndrome
  • Stale fish syndrome
  • TMAU
  • TMAuria
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Overview

What is trimethylaminuria?

What are the signs and symptoms of trimethylaminuria?

What causes trimethylaminuria?

How is trimethylaminuria inherited?

How might trimethylaminuria be treated?

What is trimethylaminuria?

Trimethylaminuria (TMAU) is a metabolic disorder in which an individual is not able to break down trimethylamine into smaller parts. Trimethylamine is the substance that gives fish their distinctive smell. Since an individual with TMAU is unable to break down trimethylamine, they tend to have a fish-like odor coming from their sweat, urine, reproductive fluids, and breath. TMAU is caused by a mutation in the FMO3 gene and is inherited in an autosomal recessive pattern. This condition can be diagnosed by a test to measure the amount of trimethylamine in urine. Genetic testing can also be performed using a blood sample to diagnose TMAU. Although there is no cure for TMAU, the condition can be managed by reducing the amount of trimethylamine in the body. For example, people with TMAU can modify their diet to avoid foods with high levels of trimethylamine.[1][2]
Last updated: 1/27/2014

What are the signs and symptoms of trimethylaminuria?

Trimethylamine accumulates in the body of individuals with trimethylaminuria. The trimethylamine gets released in the person's sweat, urine, reproductive fluids, and breath, giving off a strong fish-like odor. This odor may be constantly strong for some people with trimethylaminuria, but most of the time the odor is moderate and varies in intensity. Individuals with this condition do not have any physical symptoms, and typically appear healthy.[1]
Last updated: 1/27/2014

What causes trimethylaminuria?

People with trimethylaminuria lack the enzyme called flavin-containing monooxygenase 3 (FMO3), which is produced in the liver.[2] FMO3 is responsible for breaking down compounds that contain nitrogen, sulfur, or phosphorous.[2] This enzyme is produced by the FMO3 gene. A mutation in this gene prevents the enzyme from working properly, so it is unable to break down compounds like trimethylamine.  Because trimethylamine has a fish-like odor, as it builds up in a person’s body the odor becomes noticeable. Not all of the functions of the FMO3 enzyme are known, so physicians don't know what other symptoms may be associated with trimethylaminuria.[3][1]

 

There are several mutations, or alterations in the gene, that are associated with trimethylaminuria.  Researchers believe that a variety of genetic mutations (not yet discovered) can lead to the variability of the time of onset of symptoms and the strength of the odor. They also suspect that stress and diet play a role in triggering symptoms.[3][1][2]

Last updated: 1/27/2014

How is trimethylaminuria inherited?

Trimethylaminuria is usually inherited in an autosomal recessive pattern, which means that which means that both copies of the gene in each cell have mutations in order for a person to have symptoms. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene and are referred to as "carriers" of the condition. .[3]

Since trimethylaminuria usually requires two mutations to cause symptoms, typically neither parent of an individual with trimethylaminuria has any symptoms.   Occasionally, however, carriers of one copy of an FMO3 mutation may experience mild symptoms of trimethylaminuria or have temporary episodes of fish-like odor.[3]

When two people who are carriers of an autosomal recessive condition have a child, there is a 25% (1 in 4) chance that the child will have the condition, a 50% (1 in 2) chance that the child will be a carrier like each of the parents, and a 25% (1 in 4) chance that the child will not have the condition and not be a carrier.
Last updated: 1/27/2014

How might trimethylaminuria be treated?

Although there is no cure for trimethylaminuria, the following are some ways to reduce symptoms of odor:[3][2]

 

  • Avoiding foods containing trimethylamine and its precursors (choline and trimethylamine N-oxide). Trimethylamine is present in high levels in milk obtained from wheat-fed cows. Choline is present in high amounts in: eggs, liver, kidney, peas, beans, peanuts, soy products, brussel sprouts, broccoli, cabbage, and cauliflower, lecithin, and lecithin-containing fish oil supplements. Trimethylamine N-oxide is present in seafood. Freshwater fish have lower levels of trimethylamine N-oxide than fish from the ocean.
  • Taking low doses of antibiotics to reduce the amount of bacteria in the gut. This decreases the amount of trimethylamine that is made by bacteria.
  • Taking laxatives can decrease the amount of time trimethylamine stays in the intestines and reduce the amount of trimethylamine made in the gut.
  • Taking certain nutritional supplements to decrease the concentration of trimethylamine in the urine.
  • Activated charcoal taken at a dose of 750mg twice daily for ten days. Copper chlorophyllin taken at a dose of 60mg three times a day after meals for three weeks.
  • Using soaps with a moderate pH, between 5.5 and 6.5. Trimethylamine is a strong base (pH 9.8), thus soaps with pH closer to that of normal skin help remove the secreted trimethylamine.
  • Taking riboflavin (vitamin B2) supplements to enhance any existing FMO3 enzyme activity (which breaks down trimethylamine). Recommended intake is 30-40mg taken 3-5 times per day with food.
  • Avoiding factors that promote sweating, such as exercise, stress, and emotional upsets.

NOTE: Individuals should follow the treatment advice of their healthcare provider and should not attempt to self-administer these treatment approaches. Medications and supplements can have unintended interactions, and dietary restrictions can result in nutritional deficits.

Choline is essential for nerve and brain development in fetuses and infants, therefore, pregnant and breast-feeding women should consult with their health care provider before restricting their dietary choline.[3]

People with trimethylaminuria may also find the following to be helpful:[3]  

  • Behavioral counseling to help with depression and other psychological symptoms.
  • Genetic counseling to better understand how they developed the condition and to be aware of the risks of passing this disease on to their children. Visit the Healthcare Services section to find a list of online resources that can assist you in finding a genetics clinic near you.
Last updated: 1/27/2014

References
  1. Trimethylaminuria. Genetics Home Reference Web site. January 2013; http://ghr.nlm.nih.gov/condition=trimethylaminuria. Accessed 1/27/2014.
  2. Phillips IR, Shephard EA. Trimethylaminuria. GeneReviews. April 19, 2011; http://www.ncbi.nlm.nih.gov/books/NBK1103/. Accessed 1/27/2014.
  3. Learning about Trimethylaminuria. National Human Genome Research Institute Web site. July 20, 2011; http://www.genome.gov/11508983. Accessed 1/27/2014.


Other Names for this Disease
  • Fish malodor syndrome
  • Fish odor syndrome
  • Stale fish syndrome
  • TMAU
  • TMAuria
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.