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Genetic and Rare Diseases Information Center (GARD)

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Trimethylaminuria


Other Names for this Disease
  • Fish malodor syndrome
  • Fish odor syndrome
  • Stale fish syndrome
  • TMAU
  • TMAuria
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Your Question

Although I have not been diagnosed with trimethylaminuria, I have been having a foul odor for about 2 years.  Can you tell me more about this condition? How can I be tested for this condition? How is it treated? Is there a cure for trimethylaminuria?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

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

Is trimethylaminuria more common in certain people?

The syndrome seems to be more common in women than men, but scientists don't know why.[3] Scientists suspect that female sex hormones, such as progesterone and/or estrogen, exaggerate the symptoms.[3] There are several reports that the condition worsens at times when there is an increase in these hormones in the body. This occurs during puberty, just before and during menstrual periods, after taking oral contraceptives, and around menopause.[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

Is testing available for trimethylaminuria?

Yes. Trimethylaminuria can be diagnosed through a urine test that measures the amount of trimethylamine in the urine. If an individual is on a non-restricted diet, urine testing should be performed on two separate occasions.

 

Carrier testing is also available for trimethylaminuria. This test is called either a 'TMA challenge' or a 'TMA load' test. It involves giving an individual a 600mg capsule of trimethylamine. Then the amount of trimethylamine that is not broken down and excreted in the urine is measured. If an individual is a carrier, the amount of trimethylamine that is not broken down is 20-30% of total trimethylamine excreted. For people who are not carriers, the amount of trimethylamine that is not broken down is less than 13%.[3]

The laboratories listed below provide clinical diagnostic testing for elevated levels of trimethylamine in the urine. The Information Center provides the names of these centers for informational purposes only, not as an endorsement of the institutions' products or services. Please note that some laboratories do not accept direct contact from patients. Therefore, we recommend that you work with a medical or genetics professional to contact these laboratories for further information. 

Arkansas Children's Hospital
Metabolic Laboratory
Phone: (501) 364-1300
Web site: http://www.archildrens.org/documents/TMAinfoLab.pdf

Monell Chemical Senses Center
University of Pennsylvania
Phone: 267-519-4700
Contact: George Preti, PhD 
E-mail: preti@monell.org  
Web site: http://www.monell.org/contact_us/tmau/
For more information, patients can send an e-mail to: bodyodorinfo@monell.org 

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
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

Can trimethylaminuria be cured by replacing the missing enzyme?

Unfortunately at this time, enzyme replacement therapy is not an option in the management of trimethylaminuria.[3]
Last updated: 1/27/2014

References