Trimethylaminuria

Trimethylaminuria (TMAU), also known as fish odor syndrome or fish malodor syndrome^[1], is a rare genetic disease that causes a defect in the body's ability to normally produce Flavin containing monooxygenase 3 (FMO3).^[2][3]

When FMO3 is compromised, the body loses the ability to properly breakdown trimethylamine. Trimethylamine is consumed through the diet and when not properly broken down, through a process called N-Oxygenation, builds up and is released in the person's sweat, urine and breath, giving off a strong fishy odor.

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Symptoms

Trimethylamine causes an offensive body odor that resembles rotting eggs and is released in the person's sweat, urine and breath, giving off a strong fishy odor. People affected with TMAU may suffer from an unusual body odor that is volatile and pungent and may negatively affect their social life, work, and school. In a person with TMAU the odor varies depending on many known factors, including the types of foods eaten, hormonal changes, other odors in the space, and our individual sense of smell and odor perceptions. The malodor has been described variously as cigarette/cigar smoky, garbagelike, feces, urine, funky, fishy and more.

Incidence

TMAU is a life-disruptive disorder caused by both genetic and environmental factors. Living with TMAU is challenging, and it can adversely affect the livelihood of adults who have it and their families. Children with the condition could find it difficult to go through school without facing tormentors and bullies. There are various online support groups that have been created to help those in with malodor issues such as TMAU.

Diagnosis

Measurement of urine amino acids is the standard screening test. A blood test is available to provide genetic analysis. The prominent enzyme responsible for TMA N-oxygenation is the FMO3 gene. TMAU is a rare disorder. There used to be very limited medical knowledge readily available about most rare disorders or how to get tested for them. However, health care professionals willing to go the extra mile can now get helpful information from genetic and rare disorder databases.

One of the tests for trimethylaminuria is a urine test for elevated levels of trimethylamine.

A similar test can be used to identify carriers of this condition - those individuals who carry one copy of a mutated gene but do not have symptoms. In this case, the person would be given a high dose of choline (one of the precursors of trimethylamine) and then have their urine tested for elevated levels of trimethylamine.

There also is a DNA test that can detect the genetic defect.

Treatment

Currently, there is no cure and treatment options are limited. Although there is no perfect cure for trimethylaminuria, it is possible for some people with this condition to live relatively normal, healthy lives without the fear of being shunned because of their unpleasant odor. Getting tested is an important first step. Ways of reducing the odor include:

• Avoiding foods such as eggs, legumes, certain meats, fish, and foods that contain choline, nitrogen, and sulfur.
• Taking low doses of antibiotics to reduce the amount of bacteria in the gut.
• Using soaps with a moderate pH, between 5.5 and 6.5.
• At least one study^[4] has suggested that the daily intake of charcoal and/or copper chlorophyllin may be of significant use in improving the quality of life of individuals suffering from TMAU, the success rates vary:
  • 85% of people tested completely lost their "fishy" odor.
  • 10% partially lost their odor.
  • 5%, though, kept the scent.

However, whilst they may be beneficial in some cases, many people in trimethylaminuria support groups who have tried charcoal and copper chlorophyllin have reported disappointing results.

Also helpful are:

• Behavioral counseling to help with depression and other psychological symptoms.
• Genetic counseling to better understand their condition.

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. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene. Carriers may have mild symptoms of trimethylaminuria or experience temporary episodes of fish-like body odor.

Mutations in the FMO3 gene, which is found on the long arm of chromosome 1, cause trimethylaminuria. The FMO3 gene makes an enzyme that breaks down nitrogen-containing compounds from the diet, including trimethylamine. This compound is produced by bacteria in the intestine as they digest proteins from eggs, meat, soy, and other foods. Normally, the FMO3 enzyme converts fishy-smelling trimethylamine into trimethylamine N-oxide which has no odor. If the enzyme is missing or its activity is reduced because of a mutation in the FMO3 gene, trimethylamine is not broken down and instead builds up in the body. As the compound is released in a person's sweat, urine, and breath, it causes the strong odor characteristic of trimethylaminuria. Researchers believe that stress and diet also play a role in triggering symptoms.

There are more than 40 known mutations associated with TMAU.^[5][6] Loss-of-function mutations, nonsense mutations, and missense mutations are three of the most common. Nonsense and missense mutations cause the most severe phenotypes. Although FMO3 mutations account for most known cases of trimethylaminuria, some cases are caused by other factors. A fish-like body odor could result from an excess of certain proteins in the diet or from an increase in bacteria that normally break down trimethylamine in the digestive system. A few cases of the disorder have been identified in adults with liver damage caused by hepatitis.

The evolution of the FMO3 gene has recently been studied including the evolution of some mutations associated with TMAU. ^[7]

References

This article incorporates public domain text from The U.S. National Library of Medicine and The National Human Genome Research Institute