AB134. Trimethylaminuria: report of two cases in Ramathibodi hospital

Background: Trimethylaminuria (TMAU), or fish-odor syndrome, is a rare metabolic disorder with clinical characteristic of rotten fish-like body odor due to excessive trimethylamine excretion, caused by flavin-containing monooxygenase 3 (FMO3) deficiency leading to defective hepatic trimethylamine metabolism. About 200 cases have been reported world-wide, but only five have previously been reported in Thailand. Here, we report two further unrelated cases of trimethylaminuria presented in Ramathibodi hospital.

Case presentation: (I) The first case is a 55-year-old Thai female who presented with foul-smelling body odor, resembling rotten fish, for 20 years, resulting in self-embarrassment and social anxiety. This did not relate to any activity or condition. Her mother also experienced the same condition, but with milder severity. Sequencing of her FMO3 gene showed heterozygous c.769G>A (p.Val257Met) variant, which could cause reduction in TMA N-oxygenation activity. Her symptom improved after treatment with activated charcoal. Her mother declined any diagnostic investigation for trimethylaminuria. (II) The second case is a 19-year-old woman, who suffered from rotten fish-like body and urine odor for 3 years. She has two younger brothers, none of whom experienced a similar problem. Sequencing of her FMO3 gene showed heterozygous c.472G>A (p.Glu158Lys) and c.923A>G (p.Glu308Gly) mutations, which could also cause reduction in TMA N-oxygenation activity. She was advised to avoid food containing high choline and trimethylamine (eggs, legumes, Brassica vegetables, and marine fish). Her fishy body and urine odor improved after dietary restriction.

Conclusions: We report two cases of FMO3 deficiency resulting in symptoms of primary trimethylaminuria, with identified FMO3 gene mutation, which was successfully treated with activated charcoal in the first case, and dietary restriction in the second case. Although it is rare, trimethylaminuria causes patients to suffer from psychosocial problems. Early diagnosis and appropriate treatment remain very important steps that could help patients suffering from trimethylaminuria, which should be suspected in patients who report fishy body odor. Treatment includes a combination of low precursor diet with intermittent antibiotics and sequestering agents (activated charcoal and copper chlorophyllin). Genetic counseling is essential, especially in primary trimethylaminuria caused by identified FMO3 gene mutation.

Keywords: Trimethylaminuria (TMAU); flavin-containing monooxygenase 3 (FMO3); fish-odor syndrome