title: 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.
authors.affiliation: Department of Pharmacology, St. Mary's Hospital, Medical School, London.
authors.forename: M
authors.initials: M
authors.lastname: al-Waiz
authors.forename: R
authors.initials: R
authors.lastname: Ayesh
authors.forename: S C
authors.initials: SC
authors.lastname: Mitchell
authors.forename: J R
authors.initials: JR
authors.lastname: Idle
authors.forename: R L
authors.initials: RL
authors.lastname: Smith
mesh_terms: D000284:Administration, Oral; D000328:Adult; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics* / Q000652:urine; D008744:Methylamines / Q000008:administration & dosage / Q000652:urine*; D008875:Middle Aged
chemical_list: D008744:Methylamines; C005855:trimethyloxamine; C023336:trimethylamine