Biochemical basis: failure to oxidize trimethylamine to the odorless trimethylamine N-oxide
Types:
(1) primary genetic defects in the flavin monooxygenase (FMO) enzymes, which may be polymorphic
(2) transient/intermittent
(2a) acquired after a viral or other infection
(2b) associated with menstruation in women
(2c) during childhood
(2d) excess dietary intake of precursor compounds choline or carnitine, which are converted by enteric bacteria to trimethylamine
(2e) excess dietary intake of trimethylamine
As with other inherited disorders, the most severe forms are seen in patients who have more severe defects in N-oxidation. Some of the patients with transient forms may be a carrier or heterozygous for the enzymatic defects.
Clinical features:
(1) The person smells of rotting fish.
(2) This results in severe problems at work and in inter-personal relationships.
(3) The person may become isolated and severely depressed.
(4) The condition may be exacerbated by stress or fever.
(5) Patients with the primary form will usually have a family history of the disorder.
The odor is due to the presence of trimethylamine in the urine, sweat, breath and body fluids.
Oral administration of 600 mg of trimethylamine can help identify affected persons.
