Trimethylaminuria E88.8

Trimethylaminuria (TMAU) is a rare, globally widespread, autosomal recessive inherited metabolic disorder (Doyle S et al. 2019; Guo Y et al. 2017; Hernangómez Vázquez S et al.2019; Kim JH et al. 2017). The cause is a mutation of the flavin-containing monooxygenase 3 (FMO3), an enzyme whose coding gene (FMO3 gene) is located on chromosome 1q23-q25.

The mutation results in the absence or deficiency of functional monooxygenase 3, an enzyme that converts trimethylamine into the odourless trimethylamine nitric oxide (TMA-N oxide) in the liver of healthy humans (Doyle S et al. 2019). The enzyme deficiency leads to the fact that the fishy-smelling substance trimethylamine (TMA) cannot be metabolized, or only insufficiently. Trimethylamine is excreted mainly through sweat, breathing air and urine.

Determination of the trimethylamine concentration in urine. The TMAO/TMA quotient is of importance.

No specific therapy option. Restrictions of foods rich in choline or lecithin, from which trimethylamine is produced, are recommended. It is therefore recommended not to eat eggs, offal, soy products, legumes, cabbage, etc. Sea fish and seafood in which trimethylamine N-oxide is present should also be avoided.

The clinical picture is already detectable at birth. The olfactory symptoms often intensify during puberty. In women the odour intensifies during menstruation. The use of oral contraceptives also leads to an increased odour burden.

1. Doyle S et al (2019) The genetic and biochemical basis of trimethylaminuria in an Irish cohort. JIMD Rep 47:35-40.
2. Guo Y et al (2017) Genetic analysis of impaired trimethylaminuria metabolism using whole exome sequencing. BMC Med Genet 18:11.
3. Hernangómez Vázquez S et al.(2019) Trimethylaminuria: three differentmutations in a single family. Nutr Hosp 36:492-495.
4. Kim JH et al (2017) A compound heterozygous mutation in the FMO3 gene:the first pediatric case causes fish odor syndrome in Korea. Korean J Pediatr 60:94-97.
5. Kılıç M et al. (2017) Primary trimethylaminuria (fish odor syndrome) and hypothyroidism in an adolescent. Turk J Pediatr 59:614-616.
6. Phillips IR et al (2019) Flavin-containing monooxygenase 3 (FMO3): geneticvariants and their consequences for drug metabolism and disease. Xenobiotica 1:1-15.