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. Individuals with this condition do not have any physical symptoms, and typically appear healthy.
The condition seems to be more common in women than men, for unknown reasons. 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.
This odor varies depending on many known factors, including diet, hormonal changes, other odors in the space, and individual sense of smell.
Measurement of urine for the ratio of trimethylamine to trimethylamine oxide is the standard screening test. A blood test is available to provide genetic analysis. The prominent enzyme responsible for TMA N-oxygenation is coded by the FMO3 gene.
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.
Currently, there is no cure and treatment options are limited. However, 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, carnitine, nitrogen, and sulfur
Taking low doses of antibiotics to reduce the amount of bacteria in the gut
Using slightly acidic detergents with a pH between 5.5 and 6.5
At least one study 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 mild forms of TMAU. Success rates varied:
85% of people tested completely lost their "fishy" odor
10% partially lost their odor
5% 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.
Trimethylaminuria has an autosomal recessive pattern of inheritance.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. 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. These compounds are 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. 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 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.