Trimethylaminuria: The detection of carriers using a trimethylamine load test

Abstract

A method potentially of value for investigating putative heterozygotes or carriers of trimethylaminuria by using a single oral dose of trimethylamine (TMA) is described. For healthy volunteers under normal dietary condition and following oral challenge with 300 mg and 600 mg TMA-base, over 90% of the urinary TMA was excreted in the form of TMA (93.6 +/- 1.6%). However, at a dose level of 900 mg TMA-base, there was clear evidence of saturation of the N-oxidation reaction as urinary TMA excretion declined to 77.2% (range 74.8-78.9) of the total dose of TMA. By contrast, in pedigree studies based upon propositi with trimethylaminuria, several parents were identified who showed clear evidence of saturation of the N-oxidation of TMA at the 600 mg TMA-base dose level, but not at 300 mg TMA-base or under normal dietary condition. In these individuals, the proportion of urinary TMA as trimethylamine N-oxide (TMAO) declined to (77.3 +/- 1.7%). Accordingly we propose that the oral administration of 600 mg TMA-base and the analysis of the following 0-8-h urine collection may be useful for the investigation of possible carriers of trimethylaminuria.

Clinical utility gene card for: Trimethylaminuria

“…31 However, heterozygous carriers can be detected after administration of a 'trimethylamine load' of 600 mg, given orally in a gelatine capsule. 21,32 No &…”

The N‐oxidation of trimethylamine in a Jordanian population.

“…However a condition trimethylaminuria, known colloquially as the fishodour syndrome, exists in which affected individuals have a compromised ability to N-oxidise TMA and as such excrete free TMA in their breath, sweat, urine and other bodily secretions which results in a characteristic fish-like odour [6,7]. Such individuals appear to be homozygous for an allele which determines an impaired ability to perform this N-oxidation reaction [4,8,9]. Carriers (heterozygotes) of this defect can be identified on the basis of a compromised ability to N-oxidise TMA under normal dietary conditions and after oral challenge with a dose of TMA sufficient to saturate their N-oxidation capacity [9].…”

“…Such individuals appear to be homozygous for an allele which determines an impaired ability to perform this N-oxidation reaction [4,8,9]. Carriers (heterozygotes) of this defect can be identified on the basis of a compromised ability to N-oxidise TMA under normal dietary conditions and after oral challenge with a dose of TMA sufficient to saturate their N-oxidation capacity [9]. Using these methods the prevalence of heterozygotes in a British white population appears to be at least 1% [4].…”

Trimethylaminuria (Fish-Odor Syndrome)

“…29 Oral challenge with TMA is helpful as far as identifying possible carriers is concerned. [30][31][32][33] The genotypic contribution to phenotypic expression in trimethylaminuria has been studied using the combination of proton nuclear magnetic resonance spectroscopy and gene sequencing methods. [34][35][36][37] Gas chromatography, isotope dilution, and solid-phase microextraction are other techniques that have been used to detect increased amounts of TMA in the urine of patients with suspected trimethylaminuria.…”