Trimethylaminuria FMO3 Gene Mutation Analysis R51G

Trimethylaminuria is a disorder in which the body is unable to break down trimethylamine, a pungent-smelling chemical compound described as smelling like fish, rotten eggs, spoiled fish, garbage, or urine. This compound accumulates in the body, causing those affected to give off a strong smell of sweat, urine and breath. Odor intensity may vary over time. Odor 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 the FMO3 gene, located on the long arm of chromosome 1 (1q24.3), which encodes the family of flavin monooxygenases (FMO) that break down nitrogenous compounds in the diet, including trimethylamine, which It is the molecule that imparts the odour. of fish This compound is produced by intestinal bacteria for the digestion of proteins from eggs, liver, legumes (such as soybeans and peas), certain types of fish and other foods. Typically, the enzyme converts the strong-smelling trimethylamine into another molecule that has no odor (trimethylamine-N-oxide), which is thus eliminated from the body. If the enzyme is absent or its activity is reduced due to a mutation in the FMO3 gene, trimethylamine is not processed correctly and can accumulate in the body. This enzyme also breaks down some drugs, such as anticancer drugs (tamoxifen), codeine, ketoconazole, some antidepressants, or nicotine tobacco.

More than 25 mutations in the FMO3 gene have been described in individuals affected by trimethylaminuria, giving rise to a small non-functional version of the enzyme. Some mutations result in amino acid changes in the enzyme, which change its shape and alter its function. Although FMO3 gene mutations account for the majority of cases of trimethylaminuria, the condition can also be caused by other factors. Strong body odor can result from an excess of certain dietary proteins or an abnormal increase in trimethylamine-producing bacteria 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 new mutation in the first documented case in Spain Clin Med, 2003:.... 120: 219-217) , interacting with trimethylulaminuria .

There are also single nucleotide polymorphisms (SNPs), such as V257M, E158K and E308G, among others that appear in multiple publications. These polymorphisms can be found in individuals without symptoms of trimethylaminuria, but enzyme activity can be reduced and become more evident when dietary precursors that generate higher amounts of trimethylamine (TMA) are ingested, such as products rich in choline or some vegetables (Brassica spp. : kale, cabbage, cauliflower, broccoli, etc.), which inhibit the action of ingested FMO3. Likewise, it can occur under certain physiological conditions (eg, menstruation), or in individuals who have a copper deficiency or who have already had the activity of the FMO3 enzyme partially inhibited by certain adverse drug interactions or alcohol intake. However, when individuals are homozygous for E158K E308G and/or have these two associated polymorphisms, symptomatic FMO3 deficiency may manifest. Likewise, the E158K/E308G haplotype 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 each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have one copy of the mutated gene, but usually show no signs or symptoms of the disease.

Tests at IVAMI: at IVAMI we perform detection of mutations associated with Trimethylaminuria, by means of complete PCR amplification of exons of the FMO3 gene, and subsequent sequencing.

Recommended samples: EDTA blood collected for separation of blood leukocytes, or sample card impregnated with dried blood (IVAMI can send the card to deposit the blood sample).