Learning About Trimethylaminuria

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


Learning About Trimethylaminuria

What is trimethylaminuria?

Trimethylaminuria is a metabolic condition in which an individual is not able to convert trimethylamine into a compound called trimethylamine N-oxide. Trimethylamine is the compound that gives fish the fishy odor. Trimethylamine N-oxide does not smell. Trimethylaminuria, has been around for centuries, but has only gained scientific recognition and support in the past 30 years.

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What are the symptoms of trimethylamineuria?

Trimethylamine builds up in the body of patients with trimethylaminuria. The trimethylamine gets released in the person's sweat, urine, reproductive fluids, and breath, giving off a strong fishy odor. Some people with trimethylaminuria have a strong odor all the time, but most have a moderate smell that varies in intensity over time. Other than the strong fishy odor, individuals with this condition typically appear healthy.

The condition seems to be more common in women than men, but scientists don't know why. Scientists suspect that female sex hormones, such as progesterone and/or estrogen, aggravate symptoms. There are several reports that the condition worsens around puberty. In women, symptoms can worsen just before and during menstrual periods, after taking oral contraceptives, and around menopause.

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What causes trimethylaminuria?

People with trimethylaminuria have an impaired version of the enzyme flavin-containing monooxygenase 3 (FMO3). This is the enzyme that converts trimethylamine to to trimethylamine N-oxide. FMO3 is produced by the liver and is a member of a family of similar enzymes responsible for metabolizing compounds that contain nitrogen, sulfur, or phosphorous. The enzyme is coded for by the FMO3 gene. Trimethylaminuria may be caused by a variety of genetic changes to the FMO3 gene. Not all of the functions of the FMO3 enzyme are known, so physicians don't know what other symptoms besides odor may be associated with trimethylaminuria.

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Is trimethylaminuria inherited?

Yes. Trimethylaminuria is usually inherited in an autosomal recessive fashion, which means that two non-functioning FMO3 genes are usually needed for a person to have symptoms. Both parents of an individual with trimethylaminuria are "carriers" of the condition, in other words, they both carry one copy of an altered gene for FMO3. Since this condition usually requires two altered genes to cause symptoms, typically neither parent of an individual with trimethylaminuria has any symptoms. Sometimes, "carriers" of one copy of an FMO3 mutation may have mild symptoms of trimethylaminuria or have temporary episodes of fish-like odor. Due to the variability of symptoms people with trimethylaminuria experience, researchers think that different genetic mutations in FMO3 can influence the symptoms of the disease, affecting time of onset and how strong the odor is. They also suspect that stress and diet play a role in triggering symptoms.

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How is trimethylaminuria diagnosed?

A urine test is used to diagnose trimethylaminuria. The person's urine is tested to look for higher levels of trimethylamine. Testing can be done by giving choline by mouth followed by urine collection a certain number of times over a 24 hour period. Urine testing should be performed on two separate occasions when the individual is on a non-restricted diet. The test measures the ratio of trimethylamine to trimethylamine N-oxide present in the urine.

A carrier of this condition can be identified by the "TMA challenge" or a "TMA load" test. This involves giving an individual a 600 dmg pill of trimethylamine (TMA). Carriers of trimethylaminuria excrete 20-30 percent of total trimethylamine as the free unmetabolized amine and the rest as trimethylamine N-oxide. Non-carriers excrete less than 13% of the dose as trimethylamine. Gene testing called gene sequencing can be used to look for mutations in the FMO3 gene. Gene testing is currently available only through research laboratories.

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How is trimethylaminuria treated?

There is currently no cure for trimethylaminuria. However, it is possible for people with this condition to live normal, healthy lives. The following are some ways a person with trimethylaminuria can lower symptoms of odor:

It is important that a person who has trimethylamuinuria follow the treatment advice of their health care provider. They 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.

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

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Can trimethylaminuria be cured by replacing the enzyme FMO3?

Unfortunately at this time, enzyme replacement therapy with the enzyme FMO3, which when absent, is believed to cause the condition, is not an option in the management of trimethylaminuria.

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What laboratories offer testing for trimethylaminuria?

The following laboratories are able to assist in the diagnostic testing of patients who may have trimethylaminuria. Please note that some of these laboratories do not accept direct contact from patients. Therefore, it is recommended that you work with a medical or genetics professional to contact the laboratories for further information.

The laboratories listed below recently began performing clinical diagnostic testing for elevated levels of trimethylamine for patients in the United States.

The GeneTests Web site lists one laboratory as performing clinical diagnostic testing. This laboratory is located in Canada. However, they accept samples from people in the United States. To find out more about this laboratory, select the 'GeneTests' icon at the top of the page at the following URL: www.geneclinics.org. Use 'trimethylaminuria' as your disease search term and click on either the 'Research' or 'Testing' icon for the laboratory's contact information. Note: This laboratory does not accept direct contact from patients. Work in conjunction with a health care provider or genetics professional to contact the laboratory and learn more about the clinical diagnostic testing the laboratory offers.

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Clinical Research on Trimethylaminuria

Currently, NHGRI is not conducting studies on Trimeththylaminuria.

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Additional Resources for Trimethylaminuria

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Last Updated: July 20, 2011