When a 12-month-old boy in Portugal developed an unexpected and persistent smell similar to rotting fish, his parents were unsettled. The child appeared healthy, showed no signs of infection, and behaved normally. Yet the odor continued. After multiple clinical evaluations and ruling out common causes, doctors identified the source: a rare metabolic condition known as trimethylaminuria, commonly called fish odor syndrome.
Doctors eventually determined that the underlying cause was biochemical rather than infectious.
Trimethylaminuria is a metabolic condition in which the body is unable to break down a compound called trimethylamine (TMA). TMA is produced when the gut digests certain foods, particularly those containing choline, carnitine, or lecithin, nutrients commonly found in fish, eggs, meat, and some legumes.
In most people, an enzyme produced by the FMO3 gene converts TMA into a non-odorous compound that is then safely excreted. In individuals with trimethylaminuria, this process is either reduced or absent. As a result, TMA accumulates and leaves the body through sweat, breath, and urine, producing a noticeable fish-like smell.
The disorder is also known by the abbreviation “TMAU”.
The inherited (primary) form is caused by mutations in the FMO3 gene and follows an autosomal recessive pattern of inheritance. ¹
The condition can be genetic (primary) or acquired (secondary). The genetic form often presents in childhood. However, symptoms may vary depending on hormonal changes, diet, stress, or illness.
Epidemiologically, the global prevalence of TMAU is estimated at about 1 in 200,000 to 1 in 1,000,000 individuals, though the true figure may be higher due to under-diagnosis. ²
Carrier rates of pathogenic FMO3 variants have been estimated at around 0.5 % to 1 % in white British populations, with higher frequencies—around 11 %—documented in certain New Guinean populations. ¹
Because the genetic form is autosomal recessive, both parents typically carry one defective gene. Carriers may be asymptomatic or may show only mild, transient odor episodes. ³
According to the Cleveland Clinic, both males and females may carry the gene, but the odor is often reported more frequently in females, possibly due to hormonal influences such as menstruation or pregnancy affecting TMA metabolism. ⁴
The condition can be genetic, caused by variants in the FMO3 gene, or it may appear temporarily due to liver disease, certain diets, or gut microbiome imbalances.
The genetic form often presents in childhood. However, symptoms may vary depending on hormonal changes, diet, stress, or illness.
According to the Cleveland Clinic, both males and females may carry the gene, but the odor is often reported more frequently in females, possibly due to hormonal influences such as menstruation or pregnancy affecting TMA metabolism.
Diagnosis usually involves:
Clinical history and symptom assessment
Measurement of trimethylamine (and its ratio to trimethylamine N-oxide) in urine—testing is often performed twice on a normal diet to confirm results ⁵
Genetic testing for FMO3 variants
A 2023 case report published in Clinical Case Reports highlighted the challenges in diagnosis, noting that children may appear otherwise completely healthy, which can delay medical recognition. ⁶
There is currently no cure for trimethylaminuria, but its symptoms can be reduced. Treatment focuses on lowering TMA production and promoting its clearance. Strategies documented in clinical studies and reviews include:
Dietary modification to limit high-choline foods
Riboflavin (vitamin B2) supplementation to enhance residual FMO3 enzyme function (dosing varies and must be clinician-guided)⁷
Short courses of antibiotics to reduce TMA-producing gut bacteria, when medically appropriate
pH-balanced skin cleansers to reduce odor-releasing sweat on the skin’s surface
These approaches are typically individualized and guided by a healthcare professional.
Long-term outcomes vary. In some children—especially mild or transient cases—the odor may diminish with age as enzyme expression matures (for example, the Portuguese case improved by age 3). ⁶
For individuals with persistent (severe) inherited TMAU, symptoms often continue lifelong. With appropriate management, most lead healthy lives with normal physical development. ⁵
While the condition does not cause physical harm, it can significantly affect daily life. Individuals with trimethylaminuria may face embarrassment, social withdrawal, or anxiety due to concerns about body odor.
A recent study reported that patients with TMAU frequently experience emotional distress, reduced self-esteem, and diminished quality of life, highlighting the need for psychological support. ⁸
Supportive counseling and clear medical communication play an important role in care.
Research continues to explore how genetic variations influence enzyme activity and how gut microbiome composition contributes to TMA production. Emerging evidence suggests that microbiome-targeted approaches and gene therapy could offer future therapeutic possibilities. ⁹
An article published in Messenger Journal emphasizes the need for greater awareness, as early recognition can help families adopt effective management strategies sooner.
Trimethylaminuria is a rare but manageable metabolic condition. The case of the 12-month-old child highlights how a seemingly unusual symptom, a persistent body odor, can serve as an important diagnostic clue. Early evaluation, clear diagnosis, and supportive management can help reduce symptom impact and improve quality of life for affected individuals and families.
What is Trimethylaminuria?
Trimethylaminuria is a metabolic condition in which the body cannot break down a strong-smelling compound called trimethylamine (TMA). As a result, TMA builds up and is released through sweat, breath, and urine, producing a fish-like odor.
Is trimethylaminuria genetic?
Yes. Many cases are caused by changes in the FMO3 gene, which affects how trimethylamine is processed. Some individuals may also experience temporary symptoms due to liver issues, hormonal changes, or gut bacteria imbalance.
Can children have trimethylaminuria?
Yes. Symptoms may appear in infancy or childhood. However, the smell can vary over time and may become more noticeable during puberty due to hormonal changes.
Is there a cure for trimethylaminuria?
There is currently no cure, but symptoms can be managed. Treatment focuses on reducing TMA production and minimizing its release through the body.
Which foods should be avoided or limited?
Foods that may increase odor include:
Fish and seafood
Eggs
Red meat and organ meat
Beans and some legumes
Soy products
Should someone with trimethylaminuria tell others about their condition?
This is a personal choice. Some people find it helpful to inform close friends, school teachers, or coworkers to avoid misunderstanding. Support groups may also help reduce isolation.
Phillips I. R. & Shephard E. A. Primary Trimethylaminuria. GeneReviews® – NCBI Bookshelf. 2020. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1103/ ¹
Awosika A. O., Anastasopoulou C. Trimethylaminuria (TMAU). StatPearls [Internet]. 2023 Jul 15. Available at: https://www.ncbi.nlm.nih.gov/books/NBK594255/ ²
Roddy D., McCarthy P., Nerney D., Mulligan-Rabbitt J., Treacy E. M. Impact of trimethylaminuria on daily psychosocial functioning. JIMD Reports. 2020. DOI: 10.1002/jmd2.12170. Available at: https://pubmed.ncbi.nlm.nih.gov/33473342/ ³
National Human Genome Research Institute. About Trimethylaminuria (TMAU). Available at: https://www.genome.gov/Genetic-Disorders/Trimethylaminuria ⁴
National Organization for Rare Disorders (NORD). Trimethylaminuria (TMAU). Available at: https://rarediseases.org/rare-diseases/trimethylaminuria/ ⁵
Chalmers R. A., Cashman J. R., et al. Diagnosis and management of trimethylaminuria (FMO3 deficiency). J Am Diet. 2006; etc. (excerpted) — for biochemical/clinical data see PubMed: https://pubmed.ncbi.nlm.nih.gov/16601883/ ⁶
“Diagnosis and phenotypic assessment of trimethylaminuria, and its treatment with vitamin B2.” Orphanet Journal of Rare Diseases. 2019. Available at: https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1174-6 ⁷
Jazi K. Fish-Odor Syndrome. In: Springer Reference Work. 2023. Available at: https://link.springer.com/rwe/10.1007/978-3-319-66816-1_1744-1
Thompson, Helen. “A Baby Suddenly Started to Smell of Rotting Fish. Doctors Were Stumped.” Live Science. https://www.livescience.com/health/diagnostic-dilemma-a-baby-suddenly-started-to-smell-of-rotting-fish
Messenger J, Clark S, Massick S, Bechtel M. A review of trimethylaminuria: (fish odor syndrome). J Clin Aesthet Dermatol. 2013 Nov;6(11):45-8. PMID: 24307925; PMCID: PMC3848652.
Cleveland Clinic. “Trimethylaminuria (Fish Odor Syndrome).” Cleveland Clinic, 2021.
Edited by M Subha Maheswari
