Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Nov 22;13(12):961.
doi: 10.3390/biology13120961.

Exploring Trimethylaminuria: Genetics and Molecular Mechanisms, Epidemiology, and Emerging Therapeutic Strategies

Antonina Sidoti  1 , Rosalia D'Angelo  1 , Andrea Castagnetti  2 , Elisa Viciani  2 , Concetta Scimone  1   3 , Simona Alibrandi  1   3 , Giuseppe Giannini  4
Affiliations
Review

Exploring Trimethylaminuria: Genetics and Molecular Mechanisms, Epidemiology, and Emerging Therapeutic Strategies

Antonina Sidoti et al. Biology (Basel). .

Abstract

Trimethylaminuria (TMAU) is a rare metabolic syndrome caused by the accumulation of trimethylamine in the body, causing odor emissions similar to rotten fish in affected patients. This condition is determined by both genetic and environmental factors, especially gut dysbiosis. The multifactorial nature of this syndrome makes for a complex and multi-level diagnosis. To date, many aspects of this disease are still unclear. Recent research revealed the FMO3 haplotypes' role on the enzyme's catalytic activity. This could explain why patients showing only combined polymorphisms or heterozygous causative variants also manifest the TMAU phenotype. In addition, another research hypothesized that the behavioral disturbances showed by patients may be linked to gut microbiota alterations. Our review considers current knowledge about TMAU, clarifying its molecular aspects, the therapeutic approaches used to limit this condition, and the new therapies that are under study.

Keywords: gut microbiota dysbiosis; molecular genetics of FMO3; trimethylaminuria.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest regarding this study.

Figures

Figure 1
Figure 1
Catalytic cycle of FMO enzymes. This figure represents TMA oxidation by FMO enzymes, supported by NAD and FAD coenzymes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Mitchell S.C. The fish-odor syndrome. Perspect. Biol. Med. 1996;39:514–526. doi: 10.1353/pbm.1996.0003. - DOI - PubMed
    1. Humbert J.A., Hammond K.B., Hathaway W.E. Trimethylaminuria: The fish-odour syndrome. Lancet. 1970;2:770–771. doi: 10.1016/S0140-6736(70)90241-2. - DOI - PubMed
    1. Higgins T., Chaykin S., Hammond K.B., Humbert J.R. Trimethylamine N-oxide synthesis: A human variant. Biochem. Med. 1972;6:392–396. doi: 10.1016/0006-2944(72)90025-7. - DOI - PubMed
    1. Mitchell S.C., Smith R.L. Trimethylaminuria: The fish malodor syndrome. Drug Metab. Dispos. 2001;29:517–521. - PubMed
    1. Simo C., Garcia-Canas V. Dietary bioactive ingredients to modulate the gut microbiota-derived metabolite TMAO. New opportunities for functional food development. Food Funct. 2020;11:6745–6776. doi: 10.1039/D0FO01237H. - DOI - PubMed

LinkOut - more resources