What is fish odor syndrome?

Trimethylaminuria (fish odor syndrome) is a rare condition in which metabolic processes in the body do not change the chemical trimethylamine. Trimethylamine is characterized by an unpleasant odor. This is the chemical that gives rotten fish a bad smell. When normal metabolism fails, trimethylamine builds up in the body and its odor is found in a person' s sweat, urine and breath. The effects of bad breath can be socially and psychologically damaging in adolescents and adults.

The smell of fish is a clear symptom; otherwise, those affected look normal and healthy.

Trimethylamine is usually formed by exposure to choline (found in foods such as soy, liver, kidney, wheat germ, brewer' s yeast, and egg yolk) or trimethylamine N- oxide (found in salt water fish) by bacteria in the gut. Trimethylamine is then transferred to the liver, where it is converted to trimethylamine N- oxide, an odorless metabolite.

Primary trimethylaminuria is a rare metabolic disease caused by changes (mutations) in the FMO3 gene. Humans have several FMO genes, but only mutations in FMO3 cause trimethylaminuria. For unknown reasons, there are many different mutations in the FMO3 gene.

Primary trimethylaminuria is inherited as an autosomal recessive trait. A recessive genetic disorder occurs when an individual inherits the same abnormal gene for the same trait from each parent. If a person receives both the normal gene and the gene for the disease, he or she is a carrier of the disease, but usually does not show symptoms. The risk that both parents inherit the modified gene and thus have an affected child is 25% in each pregnancy. The risk of having a child who, like the parents, is a carrier is 50% in each pregnancy. There is a 25% chance that the child will receive normal genes from both parents and be genetically normal for a particular trait. The risk is the same for men and women.

All individuals carry the abnormal gene. Close relatives are more likely to carry the same abnormal gene than unrelated parents, which increases the risk of having a child with a recessive genetic disorder.

Secondary trimethylaminuria occurs as a result of treatment with high doses of food precursors for the pathogen. Symptoms occur when liver enzymes (which contain flavin monooxygenase 3) are unable to break down (metabolize) excess trimethylamine.

The smell of rotting fish is an indication, especially in severe cases. However, odor- based diagnosis is unreliable because the odor is often episodic and not everyone can perceive the smell of trimethylamine. In addition, because of the sense of smell, trimethylamineuria can be difficult to distinguish from other conditions that cause bad body odor.

Diagnosis is based on urine tests for trimethylamine and trimethylamine- N- oxide, which can differentiate between severe and mild cases. A urinalysis following the administration of a high dose of trimethylamine can differentiate disease carriers from unaffected individuals.

Genetic tests are available to differentiate between primary genetic trimethylamineuria, which causes severe symptoms, and non- genetic secondary forms of the disease.