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Sunday, May 31, 2009

Menstruation and Trimethylaminuria link in females with one FMO3 variant

This is an interesting 2007 paper by Dr John Cashman et al showing a possible link between menstruation and trimethylaminuria if the female had one or more mutants or polymorphs/variants of the FMO3 enzyme. It looks like the research was carried out in Japan, with Dr Cashman acting in a secondary role, probably including doing the DNA testing.

Transient trimethylaminuria related to menstruation

Background

Trimethylaminuria, or fish odor syndrome, includes a transient or mild malodor caused by an excessive amount of malodorous trimethylamine as a result of body secretions. Herein, we describe data to support the proposal that menses can be an additional factor causing transient trimethylaminuria in self-reported subjects suffering from malodor and even in healthy women harboring functionally active flavin-containing monooxygenase 3 (FMO3).
Methods

FMO3 metabolic capacity (conversion of trimethylamine to trimethylamine N-oxide) was defined as the urinary ratio of trimethylamine N-oxide to total trimethylamine.
Results

Self-reported Case (A) that was homozygous for inactive Arg500stop FMO3, showed decreased metabolic capacity of FMO3 (i.e., ~10% the unaffected metabolic capacity) during 120 days of observation. For Case (B) that was homozygous for common [Glu158Lys; Glu308Gly] FMO3 polymorphisms, metabolic capacity of FMO3 was almost ~90%, except for a few days surrounding menstruation showing <> 90%) metabolic capacity, however, on days around menstruation the FMO3 metabolic capacity was decreased to ~60–70%.
Conclusion

Together, these results indicate that abnormal FMO3 capacity is caused by menstruation particularly in the presence, in homozygous form, of mild genetic variants such as [Glu158Lys; Glu308Gly] that cause a reduced FMO3 function.

Full paper:Transient trimethylaminuria related to menstruation

The paper raises more questions than answers. It also goes to show how the textbook definition of TMAu (homozygous with FMO mutants) doesn't seem satisfactory. In the end, if someone says they smell of abnormal systemic smells at times (and they do), that would be the diagnosis and starting point. Usually the first step towards a TMAu diagnosis is the urine test, but it seems sensible to have the FMO3 DNA tested also, to see if there is at least a polymorph or wild type present, although even that may not be final since they may not know all polymorphs yet. FMO3 does seem to be a primary suspect in anyone who feels they have systemic body odor and maybe halitosis. However the tests cannot be deemed as 'final status' at the moment, sicne they may not know every FMO3 mutant/variant or be sure about the urine % for 'normal' etc (the % cut-off point has increased from about 50% to around 90% now). It's also unclear if there is an international agreed list of FMO3 variants, or if anyone is keeping an updated list. Also testers worldwide may use a different equation for the test, or not bother with the TMA-oxide part.

It also shows what can be achieved when real case studies are well constructed and close monitoring is used. It's unlikely in the near future that any expert would voluntarily do such an insightful TMAU test over 120 days. Sadly the medical system does not realise systemic body odor is possibly a common problem. It seems sensible to have the FMO3 DNA tested to see if there is at least a polymorph or wild type present if you have a longterm systemic body odor problem, although even that may not be final since they may not know all polymorphs yet. FMO3 does seem to be a primary suspect in anyone who feels they have systemic body odor and maybe halitosis.


keywords :
FMO3 mutant : a gene that has changed so that the normal transmission and expression of a trait is affected. Usually a bad thing. Usually 'severe'
FMO3 polymorphism : Difference in DNA sequence among individuals. Genetic variations occurring in more than 1% of a population would be considered useful polymorphisms for genetic linkage analysis.
FMO3 variant : A variant gene is usually a common very mild slightly different gene. Probably the same as a polymorphism.
homozygous : Possessing two identical forms of a particular gene, one inherited from each parent
heterozygous : Possessing two different forms of a particular gene, one inherited from each parent

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