Unpleasant Smell: A Case Report of Trimethylaminuria (Fish Odour Syndrome) in a Child

Abstract

We report a case of trimethylaminuria, also known as fish odour syndrome, in a child. This rare autosomal recessive metabolic disorder is caused by homozygous or compound heterozygous mutations in the FMO3 gene, which encodes the protein flavin-containing monooxygenase 3 (FMO3). The impaired function of this enzyme results in the accumulation of trimethylamine (TMA), a volatile, odouriferous compound excreted in the breath and bodily fluids that emits the characteristic odour of rotting fish. A previously healthy three-year-old boy began exhibiting a rotting fish-like body odour at 10 months of age after consuming swordfish. Subsequent episodes occurred with the ingestion of other types of fish. A fish-free diet temporarily resolved the odour, but symptoms recurred when fish was reintroduced. The child's growth and neurodevelopment were normal, and no abnormalities were detected during physical evaluation. Genetic testing revealed heterozygous variants in the FMO3 gene, including the intronic variant c.627+10C>G and the polymorphism c.472G>A (p.Glu158Lys), which, in combination, had the potential to cause moderate or transient symptoms. Dietary management with gradual fish reintroduction and hygiene measures were implemented. By 19 months of age, the child was consuming the recommended portions of fish without recurrence of the odour or any other symptoms. This case illustrates a transient form of trimethylaminuria, likely resulting from a combination of identified genetic variants and the FMO3 enzymatic immaturity typical in early childhood. Awareness of this condition is essential for prompt diagnosis and effective management. Dietary and hygiene strategies can effectively alleviate symptoms and improve quality of life. This case also underscores the potential spectrum of trimethylaminuria phenotypes and the value of personalised management strategies.

Keywords: fish odour syndrome; flavin-containing monooxygenase 3; metabolic disorders; trimethylamine; trimethylamine n-oxide; trimethylaminuria.