Trimethylaminuria Syndrome

An inborn error of metabolism characterized by inability to N-oxidize trimethylamine.

Fish-Odor Syndrome; TMA Syndrome; Flavin Mono-Oxygenase Syndrome; FMO Syndrome.

Epidemiologic studies have established the incidence of this condition in Britain at 1:25,000 individuals. Incidence varies with ethnicity. The populations of Ecuador and Papua New Guinea have especially high rates for the disease. The heterozygous carrier state is estimated to be as high as 1% in general population.

Although an autosomal dominant inheritance has been suggested, the possibility of an autosomal recessive trait was suggested by Ayres. Gene locus 1q23-q25. This genetic defect is characterized by the inability of the body to produce the enzyme FMO3 (flavin-containing mono-oxygenase 3), which is needed by the liver to process the protein trimethylamine (TMA). Unprocessed TMA leads to offensive body odor known as the fish-odor syndrome.

Trimethylamine is produced by gut flora in the presence of cholineand carnitine-containing foods such as saltwater fish, soya bean, and egg yolk. Trimethylamine is readily absorbed and usually undergoes N-oxidation by hepatic flavin-containing monooxygenases (FMO), which are part of the mixed function oxidase group of enzymes. In trimethylaminuria, the FMO3 isoenzyme is defective, resulting in failure of N-oxidation. Trimethylamine, which has the odor of rotting fish, is subsequently secreted in the saliva, sweat, urine, and other body fluids.

History of malodor; demonstration of trimethylamine in the urine.

Strong and repulsive odor from sweat, urine, and breath is the predominant finding. The implications are predominantly social and have resulted in poor progression at school, anxiety, and clinical depression. Suicide is not uncommon. Menstruation, stress, and pyrexia exacerbate the odor. There is one report of a patient with trimethylaminuria developing hypertension and tachycardia after ingesting tyramine-containing foods and after using ephedrine nasal drops for epistaxis. Management includes dietary restriction of carnitine and choline, and occasional use of neomycin and metronidazole to reduce bacterial production of trimethylamine.

Routine anesthetic assessment. Inquire specifically for reaction to tyramine-containing foods and catecholamine-containing medications such as nasal drops. Record drug history.

Anxiety generated by stress-related body odor may make premedication desirable for the patient.

The effect of abnormal flavin-containing monooxygenases on drug metabolism remains to be determined; however, it is advisable to use catecholamines with extreme caution because of severe hypertensive response. Desflurane should be considered relatively contraindicated.