1999 Letter in the Lancet about 'periodic' Trimethylaminuria

Of the handful of researchers who have investigated trimethylaminuria, probably the most research into the physical side of the odor problem (rather than genetic research) has been done by Dr Stephen Mitchell of  Imperial College in London (Dr SC Mitchell TMAU papers on pubmed), most of his research being in the late 80's and 90's (very little over this decade) 

In this 1999 letter to the Lancet, he comments that in his experience, many sufferers who have TMAU  are likely to be 'carriers' who only smell periodically when their FMO3 enzyme is called upon to deal with bigger loads of TMA. He explains that they have no 'reserve capacity' as normal people do. It is interesting he chooses to reply to this medical paper done by Zschocke et al, since this paper demonstrated that TMAU can include those with 2 copies of common 'mild' FMO3 variants, again being a transient form of TMAU.

TMAU, if ever discussed at medical school, is likely still regarded as a disorder affecting those with 2 mutant copies, which typically is very 'severe' and rare.

  Over the past decade we have encountered many patients who have odour problems on a mild, transient, and periodic basis. These otherwise healthy individuals are presumably heterozygotes, or compound heterozygotes, who can cope with the daily burden of trimethylamine (TMA), but have little, if any, reserve capacity when stressed by other factors and may fail to metabolically breakdown trimethylamine. To raise the general awareness of this disorder and reiterate that it “is not merely a rare recessive disorder but rather a spectrum of phenotypes of transient or mild malodour” is important, but it is also imperative to realise that fish-odour syndrome is not a simple genetic problem and that heterozygotes (carriers) may have to endure a transient and more elusive form of this complaint initiated by various, less obvious, and more ephemeral, factors.

Dr Mitchell 1999 Lancet letter about TMAU