Trimethylaminuria Syndrome

At a glance

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

Synonyms

Fish-Odor Syndrome; TMA Syndrome; Flavin Monooxygenase Syndrome; FMO Syndrome.

Incidence

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 between 0.5 and 11% in the general population.

Genetic inheritance

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 monooxygenase 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.

Pathophysiology

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

Diagnosis

History of malodor; demonstration of TMA in the urine.

Clinical aspects

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. Ingestion of tyramine-containing foods and ephedrine nasal drops may result in severe hypertension and tachycardia. Management includes dietary restriction of carnitine and choline, and occasional use of neomycin and metronidazole to reduce bacterial production of TMA.

Precautions before anesthesia

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

Anesthetic considerations

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

Pharmacological implications

Metabolism of tertiary amines such as lidocaine, bupivacaine, cimetidine, ranitidine, nicotine, benzodiazepines may result in production of TMA. It is advisable to use catecholamines with extreme caution because of severe hypertensive response. Desflurane should be considered relatively contraindicated.

References