The identification of trimethylamine excess in man: quantitative analysis and biochemical origins

The underlying biochemical causes of chronic odor problems in humans have attracted only a few investigators. This may be due, in part, to intermittent odor complaints, to the psychological problems often associated with these patients, or to the low incidence of a true metabolic disorder. One cause of intense odor is an excessive excretion of trimethylamine (TMA) in sweat, breath, and urine and was reported to be due to a defect in the liver enzyme that converts this volatile amine to its N-oxide. Other investigators have reported TMA excess as a result of liver, kidney, and/or gastrointestinal dysfunction. We report on the development of an analytical technique for urine that can be used to identify those individuals whose chronic odor is caused by a defect in their TMA pathway. A simple extension of the basic TMA analysis can be used to measure the concentration of TMA N-oxide in the affected patients. These data can, in turn, be used to demonstrate the level of activity of the N-oxide-forming enzyme in these subjects. The results obtained from using this test on more than 50 subjects indicate, in addition to a normal population, at least two types of patients with TMA excess. One group has excess TMA excretion with low activity of the N-oxide and another group shows excess TMA excretion with normal N-oxide activity.