Trimethyaminuria

What is trimethylaminuria?

Trimethyaminuria is a metabolic disorder in which an individual is not able to break down trimethylamine, the compound that gives fish their fishy odour, into smaller compounds. Consequently, trimethylamine accumulates in the body and is then released in the person's sweat, urine and breath, giving off a strong fishy odour.

Trimethyaminuria, also known as Fish Odour Syndrome, Fish Malodour Syndrome and Stale Fish Syndrome, has been around for centuries, but has only gained scientific recognition and support in the past 30 years. Some people with trimethyaminuria have a strong odour all the time, but most have a moderate smell that varies in intensity over time.

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

The condition is considered rare. However, an accurate count of individuals with this condition is not available, in part because people with trimethyaminuria often show varying degrees of symptoms. In addition, many are so ashamed of the symptoms that they conceal them rather than seek professional help. Due to the pungent odour of their bodies, people with trimethyaminuria are often depressed, maladjusted and suicidal.

People with trimethyaminuria lack the enzyme flavin-containing monooxygenase 3 (FMO3), which is produced by the liver and is part of a family of similar enzymes responsible for breaking down compounds that contain nitrogen, sulfur or phosphorous. Not all of the functions of FMO3 are known, so physicians don't know what other symptoms besides odour may be associated with trimethyaminuria.

Researchers suspect (and non-human studies have suggested) that FMO3 breaks down other substances beyond trimethylamine, such as antidepressant drugs, nicotine and tamoxifen (an anticancer drug). If this is true, people with trimethyaminuria may have side effects when taking these other drugs that people without the condition don't experience (or experience with less severity).

What causes trimethylaminuria?

The odour associated with trimethylaminuria is caused when trimethylamine is released through the affected person's sweat, breath or urine. Normally, the enzyme flavin-containing monooxygenase 3 (FMO3) transforms trimethylamine into a compound (trimethylamine-N-oxide) that has no odour. However people with trimethylaminuria either lack or have an impaired version of FMO3.

Trimethylamine is produced as a result of protein digestion. Specifically trimethylamine is produced through the metabolism of choline and trimethylamine-oxide, which are products of certain amino acids formed when protein is broken down. Choline can be found in eggs, liver, legumes (such as soy beans), and some grains (such as whole grain wheat). Trimethylamine-oxide is found in some marine fish (such as tuna). When proteins are digested by bacteria living in the intestines, trimethylamine is produced.

People are usually born with trimethylaminuria; they inherited a faulty gene for FMO3 from one of their parents. However, environmental factors, such as large doses of the drug L-carnitine and liver or kidney disease, may also play a role. Which types of bacteria are living in the gut also influences how the disorder is manifested. Some researchers believe that some types of bacteria might produce more trimethylamine than others, thus increasing symptoms.

What do we know about heredity and trimethylaminuria?

Trimethylaminuria is usually inherited in an autosomal dominant fashion, which means only one faulty gene is needed for a person to have symptoms. There are several mutations, or alterations in genetic information, that are associated with autosomal dominant inherited trimethylaminuria.

Most of the mutations are nonsense mutations in the region of chromosome 1, where the gene that codes for flavin-containing monooxygenase 3 (FMO3) resides. FMO3 is the enzyme involved in breaking down trimethylamine (the compound responsible for the fish odour).

Due to the variability of symptoms people with trimethylaminuria experience, researchers hypothesize that a variety of genetic mutations can cause the disease, affecting time of onset and how strong the odour is. They also suspect that stress and diet play a role in triggering symptoms.

How is trimethylaminuria diagnosed?

The only test for trimethylaminuria at this time 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.

How is trimethylaminuria treated?

Although there is no cure for trimethylaminuria, it is possible for people with this condition to live normal, healthy lives without the fear of being shunned because they smell like rotten fish. Ways of reducing the odour include:

• Avoiding foods containing choline and trimethylamine-oxide, the precursors of trimethylamine.
• 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.

Also helpful are:

• behavioural counselling to help with depression and other psychological symptoms.
• Genetic counselling to better understand how they developed the condition and to be aware of the risks of passing it on to the next generation.