NGLY1 deficiency
A few months back, an HN comment reminded me of a thing I read once more years ago than I realized about a boy named Bertrand who had a newly discovered and horrible genetic disorder.
Trying to find an update on the story lead me to an article indicating the boy died more than a year earlier.
I was homeless at the time I read the original and I recall doing what was, no doubt, some rambly piece of garbage blog post somewhere. So I actually have a smidgen of familiarity with this topic and spent some time thinking about it and how what I know about my condition intersects with available info on this condition.
One of the issues Bertrand had was Long QT syndrome. It was found to be drug-induced.
My understanding is this indicates magnesium deficiency, though I have no means to cite sources to back that up. But magnesium deficiency would fit with chemical derangement of the cell promoting misfolds (explained below) because pH imbalance is one means for that to happen and magnesium deficiency will tend to lead to excess acidity, in part because it typically goes hand-in-hand with calcium deficiency. These are both alkaline minerals.
In a section titled Diagnosis: N-Glycanase 1 deficiency the article finally concludes:
When that happens, the body uses an enzyme to break down the misfolded proteins and recycles the stuff it was made with. Kind of like taking apart a LEGO thing and re-using the LEGO bricks for something else.
His body couldn't do that. So the cells were filling up with useless junk.
This is a serious issue and I don't know a fix for it. As far as I know, you need to somehow get that enzyme happening to break down the misfolded glycoproteins.
But I think I do know a means to reduce the incidence of misfolds without having a cure in hand. That grows out of this research (where I looked a bunch of stuff up online) and firsthand experience.
The short version is you figure out what inputs to avoid and what inputs to prioritize in order to mitigate the degree of chemical derangement within the cell.
Chemical derangement promotes misfolds and misfolds are probably promoting chemical derangement. If you can reduce the degree of chemical derangement, you can reduce the amount of "garbage" glycoproteins that are building up within the cell.
That doesn't fix the problem but it would reduce the amount of suffering and buy you some time.
Some misfolded proteins can refold if you correct the chemical derangement. Some cannot.
I don't know how salient that is for this condition in specific, but it MIGHT mean that reducing chemical derangement would not only slow progression of the condition but even potentially mitigate the problem to some degree -- because some of the misfolded proteins might get reclaimed from the junk pile and made usable, thereby actively shrinking the junk pile.
For MY condition, this approach has proven to be a means to not only slow the progression but also reverse my symptoms. This was not anything I had any expectation would happen when I began this long, strange journey.
I was homeless at the time I read the original and I recall doing what was, no doubt, some rambly piece of garbage blog post somewhere. So I actually have a smidgen of familiarity with this topic and spent some time thinking about it and how what I know about my condition intersects with available info on this condition.
One of the issues Bertrand had was Long QT syndrome. It was found to be drug-induced.
My understanding is this indicates magnesium deficiency, though I have no means to cite sources to back that up. But magnesium deficiency would fit with chemical derangement of the cell promoting misfolds (explained below) because pH imbalance is one means for that to happen and magnesium deficiency will tend to lead to excess acidity, in part because it typically goes hand-in-hand with calcium deficiency. These are both alkaline minerals.
In a section titled Diagnosis: N-Glycanase 1 deficiency the article finally concludes:
N-Glycanase 1 plays an important role in deglycosylating misfolded proteins, allowing them to be recycled into their constituent amino acids.In layman's terms: His body had no means to "take out the garbage." The body folds proteins and glycoproteins into useful tools and when they don't fold properly, they are useless junk that is in the way.
Bertrand's cells appear to be accumulating misfolded glycoproteins.
When that happens, the body uses an enzyme to break down the misfolded proteins and recycles the stuff it was made with. Kind of like taking apart a LEGO thing and re-using the LEGO bricks for something else.
His body couldn't do that. So the cells were filling up with useless junk.
This is a serious issue and I don't know a fix for it. As far as I know, you need to somehow get that enzyme happening to break down the misfolded glycoproteins.
But I think I do know a means to reduce the incidence of misfolds without having a cure in hand. That grows out of this research (where I looked a bunch of stuff up online) and firsthand experience.
The short version is you figure out what inputs to avoid and what inputs to prioritize in order to mitigate the degree of chemical derangement within the cell.
Chemical derangement promotes misfolds and misfolds are probably promoting chemical derangement. If you can reduce the degree of chemical derangement, you can reduce the amount of "garbage" glycoproteins that are building up within the cell.
That doesn't fix the problem but it would reduce the amount of suffering and buy you some time.
Some misfolded proteins can refold if you correct the chemical derangement. Some cannot.
I don't know how salient that is for this condition in specific, but it MIGHT mean that reducing chemical derangement would not only slow progression of the condition but even potentially mitigate the problem to some degree -- because some of the misfolded proteins might get reclaimed from the junk pile and made usable, thereby actively shrinking the junk pile.
For MY condition, this approach has proven to be a means to not only slow the progression but also reverse my symptoms. This was not anything I had any expectation would happen when I began this long, strange journey.
