There is a quirk happening in one of my inkscape files where anytime I pull a guide onto the canvas, it becomes permanent. I am unable to unlock and delete it using the Edit drop down.

I can only remove it via the XML editor

I also noticed that this type of guidline has an X on it.

Is there a particular setting I have turned on in this document that makes these guides unalterable?

Yes there is a checkbox setting Edit>Lock All Guides

Guides created when the checkbox is ticked have the attribute inkscape:locked="true"

Unchecking Edit>Lock All Guides causes guides the in the document to become unlocked again.

If you have an unlocked guide, and you double click it - and tick lock in that dialogue. It will be locked. 

However I cannot see any way to unlock it on an individual basis. You can either toggle the Edit>Lock All Guides to unlock globally.

Or - in the XML editor - change inkscape:locked from true to false . However if you delete that  entry when true it does appear to remain locked, so you do have to set it to false.

Seems a bit inconsistent - but that's what I found.

Thank you for these two tips! 

1. Looks like Edit > Lock All Guides is greyed out on my end even though there is a guide present on the page.

However:

2. inkscape:lockguides="false" totally worked to solve the problem!

Thanks again!