D1.474 - Not All Fish-Related Symptoms Are Allergic: A Pediatric Case of Trimethylaminuria

Trimethylaminuria (TMAU), or fish odor syndrome, is a rare autosomal recessive metabolic disorder caused by deficiency of theFMO3 enzyme, which normally converts malodorous trimethylamine (TMA) into odorless trimethylamine N-oxide (TMAO).Pathogenic variants in the FMO3 gene lead to accumulation of TMA and its excretion in urine, sweat, and breath, producing thecharacteristic fish-like odor affecting sweat, urine, breath, and other body secretions. Systemic symptoms are usually absent, andaffected children generally show normal growth and development, with no associated gastrointestinal, neurological, or cardiovascularinvolvement. Due to the lack of other clinical manifestations, the condition may be overlooked or misattributed to food allergy.We report a pediatric case in which trimethylaminuria was identified during the diagnostic evaluation of a patient initially assessedfor suspected Food Protein–Induced Enterocolitis Syndrome (FPIES) to hake.

A 1-year-old female infant with no relevant past medical history and no allergies, who attended allergy department for the first timedue to adverse reactions after fish ingestion. At 9 months of age, one hour after first ingestion of hake (Merluccius merluccius), shedeveloped three episodes of vomiting without associated cutaneous, respiratory, or systemic symptoms.Three weeks later, after re-exposure to hake, she presented two episodes of vomiting two hours post-ingestion, again withoutcutaneous, respiratory or systemic involvement: no cardiovascular involvement. The mother additionally reported that after fishconsumption, the infant’s urine and sweat developed a noticeable fish-like odor. No other fish had been introduced. The patienttolerates all other foods. No history of drug reactions or allergic symptoms was reported.

We performed:

•Skin prick test with commercial extract of hake

•Serum total IgE determination

•Serum specific IgE to hake

•Urinary study for trimethylamine (TMA)

•Genetic study for FMO3 gene mutations (whole exome sequencing prioritized by HPO terms)

• Skin prick test with hake: Negative

• Total IgE: 17.9 kU/L (within normal range for age)

• Specific IgE to hake: <0.1 kU/L (negative)

• Urinary study for trimethylamine (TMA): Negative

• Genetic study: Two pathogenic variants identified in the FMO3 gene:◦ c.472G>A p.(Glu158Lys) in homozygosis◦ c.923A>G p.(Glu308Gly) in heterozygosis.

These variants have been previously associated with reduced enzymatic activity of FMO3 and clinicaltrimethylaminuria.

We describe a pediatric case of adverse reaction after fish ingestion in which trimethylaminuria due to pathogenic variants in theFMO3 gene was diagnosed.