paper : Mild Persistent Isolated Hypermethioninemia

disorder : persistent isolated hypermethioninemia (PIH)

enzyme at fault : Methionine S-adenosyltransferase

most common gene at fault for enzyme : MAT1A

Metabolic Body/Breath Malodors are probably due to weaknesses in an enzyme (or enzyme overload).
So any papers that may be to do with enzyme disorders that may create a smell are of interest.

Currently Health Professionals are only aware of 'smelly' enzyme disorders which are life-threatening or obviously disabling (apart from TMAU).
Usually these people will have very severe mutations and more likely to be 'homozygous' (mutation on both sides of gene).

Hypermethionemia is a very serious disorder, and so is tested for in some national/state NEWBORN SCREENING PROGRAMS.
Because of this, they will also pick up newborn data statistics on e.g. the commonality of carriers etc.

In this paper they have looked at newborn stats for HYPERMETHIONEMIA caused by MAT1A gene.
The full paper is not out, so its unknown how many were tested.

Paper (abstract. Pubmed) :
Mild Persistent Isolated Hypermethioninemia Identified through Newborn Screening in Michigan

Shades of Gray
Metabolic dept Professionals in Health systems tend to think of Metabolic Disorders as YES or NO. You either have (the severe type ... e.g. homozygous for a severe mutation) ... or not.
They don't contemplate the idea that 'carriers', especially COMPOUND carriers (carrying 2 or more different faults for same gene) may have health issues due to the faults.
Rather than being yes or no, these patients will have various SHADES OF GREY of a disorder, perhaps only having a transient smell (e.g. hypermethionemia, isovaleric acidemia).

Metabolic Consultant attitude to patients ..
Patient is comatose, obviously very ill, crippled, green, dying etc : Patient has something wrong.
You walk, talk, look ok .... Patient is normal.

In the case of MILD TRANSIENT METABOLIC BODY/BREATH MALODOR, this means they miss all cases and are unaware of the disorder.

HYPERMETHIONEMIA and SMELLING ?
In this case there must be a chance that CARRIERS may have a smell problem to do with this enzymes substrates (chemicals).

They say they picked up 16 cases of 'benign' PIH in this Newborn Screen Program.

"We describe 16 asymptomatic individuals with PIH"

Also of interest they say ...

"There were a disproportionate number of individuals with African descent in this cohort."

This seems to tie in with the MEBO Commnunity, but has also been said in a TMAU Paper by Monell.

CARRIERS CAN SMELL ?
It goes to show how even enzyme disorders which are life-threatening, limiting, crippling ... carriers may also have no problem other than a TRANSIENT SMELL, especially if they are COMPOUND carriers. (e.g. carry 2 or more variants for that gene).

Some may feel that FMO3 is still the most likely candidate gene for most cases, but it would seem sensible to also consider any ENZYMES (and so their GENEs) that may cause a smell. 

23andme and Heritage DNA consumer tests
Possibly you can look up these genes in various consumer DNA tests.
Probably they will not give info for the full gene codes, but often they show various fault codons.

Some disorders that may fall in this category
Hypermethionemia.
Isovaleric Acidemia.
FMO3 smells.

Possible Campaign Aims (write to politicians/health leaders etc)
Get Newborn DNA Screen Programs to test for FMO3 variants.
Create 'MET-BO' PROFILE TEST that includes the above enzymes/genes.

get New Posts by EMAIL : Enter your email address :

---

A EURORDIS and NORD Member Organization