Diagnostic Methods for TMAU used in Laboratoire de RMN, Hôpital Saint-Louis, Paris

In this article (2002), Dr. Michel Eugène describes the diagnosis criteria for TMAU and for the differential diagnosis from dimethylglycinuria used in Laboratoire de RMN - Exploration fonctionnelle, Hôpital Saint-Louis, Paris. Dr. Eugène states that, "The prevalence is estimated to be approximately 1 %, but is difficult to evaluate due to poor clinical awareness of the disorder."

Whenever it is available, a proton NMR spectroscopy is used in this lab, as it is the preferential method of diagnosis because it enables simultaneous measurement of urinary TMAO and TMA, and the determination of the ration TMAO / ( TMAO+TMA). It is a "...fast method which does not require any sample preparation, and enables the detection of any molecules whose concentration is higher that 10 μmolar."

The ration TMAO / (TMAO+TMA) is 96± 2% in unaffected patients following a normal diet. A drastic decrease in this ratio is observed in patients homozygote for trimethylaminuria. But an oral load of 600 mg of TMA is required to distinguish between rations of unaffected patients (95±2%) and heterozygote patients (76±3%).

This 2002 trimethylaminuria paper by Dr Michael Eugene whilst working in a Paris hospital is of interest because it gives a 'French' view of TMAU testing. Perhaps he is the 'TMAU expert in France' (not that difficult because there are so few doctors worldwide that are interested). He seems to be well read on the TMAU papers, e.g. knowing that it was recorded at the 1st TMAU Workshop that 1% could be affected. It is interesting to note the 'parameters' he has gone for with the testing. For the urine 'challenge', he has gone for 600mg of trimethylamine (TMA). All other well-known testers either go for a 'choline challenge' or a 'diet challenge'. It could be argued that the 600mg TMA test is the best, mainly because, if you have a simple trimethylamine-challenge oxidizing flaw, you can't pass this test. With the choline challenge test, they are relying on gut bacteria to change it to TMA, much like how yeast turns sugar into alcohol. If someone who done the choline challenge test had plenty of TMA-Oxide in their sample, then their FMO3 enzyme got a good workout. If there was little TMA/TMAO, not enough TMA was produced. The 600mg Trimethylamine test was originally suggested in 1989 by Dr Stephen Mitchell, Dr Smith et al of London, to detect 'carriers'. Dr Eugene is using it for all who do the test, and basing their diagnosis on the % levels produced. He also tests for dimethylglycine in the sample.

Points of interest:
His 'normal' level is very high at 96± 2%.
He expects 'carriers' (heterozygotes) to be around the 76%-95% range. In practice, perhaps 'carriers' around 76% can have transient smell issues.
He uses the 600mg trimethylamine challenge for the urine test.
He tests for dimethylglycine in the same test
He prefers using a proton NMR spectroscopy for testing

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http://www.orpha.net/data/patho/Pro/en/Trimethylaminuria-FRenPro10358.pdf
http://www.orpha.net/data/patho/GB/uk-FOS.pdf

Paper on 600mg trimethylamine test 1989 : http://www.ncbi.nlm.nih.gov/pubmed/2501587