1. Background

• also called Fish Odor Syndrome, Stale Fish Syndrome
• dietary choline is found in eggs, liver, legumes, and some grains
• dietary trimethylamine-oxide is found in some salt water fish
• dietary choline and trimethylamine-oxide are ingested then broken down by bacteria in the intestines producing trimethylamine
• trimethylamine is then absorbed and transported to the liver where it is oxidized by FMO3 to trimethylamine-N-oxide which is odorless and excreted in the urine

2. Genetic Defect

• genetic mutation within the FMO3 gene -> diminished hepatic FMO3 activity -> accumulation and massive excretion of trimethylamine in the urine and from areas of active sweating -> fishy odor due to trimethylamine
• two missense mutations have been identified in the FMO3 gene in patients with Trimethylaminuria (Dolphin, C.T. et al., Nature Genetics 17(4):491 (1997))
• in one mutation, a C-to-T transition in exon 4 results in a proline-to-leucine substitution at residue 153 which abolishes the FMO3 catalytic activity

1. Odor of Rotting Fish

• prominent in areas of active sweating (axillae, feet)
• may become more severe after puberty

2. Behavioural Manifestations

• aggressive behaviour
• poor school performance
• depression

1. Urine

• elevated trimethylamine levels

1. Supportive

• counselling for behavioural problems
• genetic counselling

2. Diet

• dietary restriction of foods containing choline and trimethylamine-oxide

3. Medical

• antibiotics may reduce the bacterial load of the gut

4. Prognosis

• excellent with normal life span