Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217

Trimethylaminuria (Trimethylaminuria) - Gen [I] FMO3.
The Trimethylaminuria is a disorder in which the body is unable to break trimethylamine, a chemical compound of pungent odor described as fishy odor, rotten eggs, fish decomposed, garbage or urine. This compound accumulates in the body, causing those affected give off a strong smell of sweat, urine and breathing. Odor intensity can vary over time. The smell can interfere with many aspects of daily life, affecting personal and professional relationships. Some people develop depression and social isolation as a result of this condition.

This process is due to mutations in FMO3 gene the located on the long arm of chromosome 1 (1q24.3), encoding the family of flavin monooxigenases (FMOs) that decomposes nitrogen containing compounds diet including trimethylamine, which is the molecule that imparts the smell of fish. This compound is produced by intestinal bacteria for digestion of the proteins of the eggs, liver, legumes (such as soybeans and peas), certain types of fish and other foods. Typically, the enzyme converts trimethylamine strong odor in another molecule that has no odor (trimethylamine-N-oxide), which is removed in this way the organism. If the enzyme is absent, or its activity is reduced due to a mutation in the FMO3 gene, trimethylamine not processed correctly and can accumulate in the body. This enzyme also decomposes some drugs, such as anticancer drugs (tamoxifen), codeine, ketoconazole, some antidepressants, or nicotine snuff.

They have been described over 25 mutations in the FMO3 gene in affected individuals trimethylaminuria, leading to a small version of the enzyme nonfunctional. Some mutations result in amino acid changes in the enzyme, which change shape and alter their function. Although FMO3 gene mutations account for most cases of trimethylaminuria, the condition can also be caused by other factors. The strong body odor can result from an excess of certain proteins in the diet or an abnormal increase of bacteria that produce trimethylamine in the digestive tract. Some cases of this disease have been found in adults with liver or kidney disease.

The R51G mutation was first described in Spain in 2003 (Ramos et al Mazón Primary trimethylaminuria or fish odor syndrome A novel mutation in the first documented case in Spain Clin Med, 2003:.... 120: 219-217), interacting with trimetiulaminuria.

There are also single nucleotide polymorphisms (SNPs), as V257M, E158K E308G and, among others referred you appear in multiple publications. These polymorphisms can be found in individuals without symptoms of trimethylaminuria, but the enzyme activity can be reduced and become more apparent when dietary precursors that generate greater amount of trimethylamine (TMA) are swallowed, such as rich products hill or some vegetables (Brassica spp .: kale, cabbage, cauliflower, broccoli, etc.), which inhibit the action of the FMO3 ingested. Likewise, it can occur under certain physiological conditions (p. Eg. Menses), or in individuals who have a deficiency of copper or has already been partially activity FMO3 enzyme inhibited by certain adverse drug interactions or intake alcohol. However, when individuals are homozygous for E158K E308G and or polymorphisms have these two partners, it may manifest symptomatic FMO3 deficiency. Likewise, the haplotype E158K / E308G, has been associated with transient symptoms of trimethylaminuria.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Trimethylaminuria, by complete PCR amplification of exons FMO3 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).