Trimethylaminuria via the FMO3 Gene

Trimethylaminuria (TMAU, OMIM 602079), also called fish-odor syndrome, is a metabolic disease that is due to the malfunction of the hepatic enzyme flavin-containing monooxygenase 3 (FMO3). The FMO3 enzyme catalyzes the oxidation of fishy-smelling trimethylamine, found in foods rich in choline and carnitine, into odorless trimethylamine-N-oxide. In patients with TMAU, FMO3 malfunction results in the accumulation of trimethylamine in the body and subsequent release in the breath, saliva, sweat, urine, and other body secretions (Cashman et al. Curr Drug Metab 4:151-170, 2003). Symptoms are intermittent and usually begin in childhood. They are exacerbated by environmental factors including diet, emotional stress, and physical activity; they may lead to psychological problems (Rehman Postgrad Med J 75:451-452, 1999). TMAU is more common and more pronounced in women than men.

Trimethylaminuria (TMAU) is inherited in an autosomal recessive manner and is caused by variants in the FMO3 gene (Dolphin et al. Nat Genet 17:491-494, 1997). To date, about 50 FMO3 variants have been reported. The majority of variants are missense. Other rare variants include nonsense, splicing, and small and large deletions. Homozygous variants in families with or without history of consanguinity and compound heterozygous variants were detected. Heterozygous carriers may develop a transient form of the disease (Allerston Mol Genet Metab 98:198-202, 2009). The FMO3 gene encodes the flavin-containing monooxygenase 3, one of several enzymes involved in the metabolism of chemical compounds that contain nitrogen, sulfur, or phosphorous.

Unknown at this time.

This test provides full coverage of all coding exons of the FMO3 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).