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
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
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.
Ayesh R, Mitchell S, Zhang A et al: The fish odour syndrome: Biochemical,
familial, and clinical aspects. BMJ