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Sunday, March 22, 2009

An Interpretation of the Nigel Manning interview : part 1

We are grateful to the recent interview Nigel Manning, the main tester of TMAU in the UK, gave to the blog recently. It greatly helps the sufferers in our understanding of the issue.

The interview can be read here

It is important that body odor sufferers are aware of the testers out there, as well as their testing procedures, influences, and thoughts on the subject. Since so few labs test for TMAU worldwide, it seems they may not have an internationally agreed test protocol. This is the first in a series of posts about the interview, in an attempt to make sense of what was said (to fully absorb the information)

These posts will be an attempt to analyze the interviews and try and fully absorb what was said. Clinical science in it's early stages can be very subjective, and you could say TMAU testing is at a very early stage of it's development (until governments realise how common it is and set standards). Anything that can be clarified later on will be corrected.


Trimethylaminuria Test Range
Nigel Mannings test range seems to be :
The ‘normal’ ranges were established early on by asking for volunteers (from the staff here at the hospital). TMA is regarded as normal if the concentration is below 11 micromoles per millimole of creatinine. TMA-oxide’s normal range is below 147 and the ratio of TMA to TMO is normal below 0.21.
TMA = trimethylamine
TMO = trimethylamine-n-oxide (the normal odorless metabolite)

Mr Manning seems to have defined the range levels himself (?), although it is clear he is well-read in TMAU medical papers. The normal concentration of TMA-creatinine is set at 11, whereas in 2 other TMAU papers the setting was around 18
Most individuals (with normal TMA N-oxidation capacity) excrete >95% of the combined TMA/TMANO load as TMANO or have a urinary TMA concentration of <18 http://www.ommbid.com/OMMBID/the_online_metabolic_and_molecular_bases_of_inherited_disease/b/abstract/part8/ch88.1

Concentration of unmetabolized TMA in the urine. A urinary concentration of free TMA of 10µg/mL (18-20 µmol/mmol creatinine) or higher, correlating with a urinary output of TMA of about 15 to 20 mg/day, appears to represent a threshold for the presence of the fishy body odor associated with the disorder [Mitchell & Smith 2001].
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&partid=1103
Mr Manning also seems to include high TMA-n-oxide levels as indicative of TMAU, whereas it is unclear if others do this, since TMA-n-Oxide is the odorless final metabolite. Presumably such a condition (high TMA-n-o) would be part of his diagnosis of the 'secondary TMAU' spectrum, since it is clear TMA was metabolized at least.

The Sheffield lab is well-known as being possibly the only lab where forum posters on english-language body odor forums indicate they were positive for TMAU2. TMAU2 is generally accepted as existing, so the question is more a case of why no-one seems to be positive for this elsewhere ?
Substrate overload of FMO3 enzyme activity resulting from either an excess of dietary precursors of TMA or variations in gut fauna, causing increased release of TMA. This type of trimethylaminuria is characterized by a high concentration of TMA in the urine, but a normal urinary TMA/TMA N-oxide ratio.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&partid=1103

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