Its looks weird, what version of PR you are using?
So, except for this option, all other changes taking placed or everything on the General Settings setting back to its default options?
Also please make sure you have “Delete all settings on Deactivation” option unchecked or off (it still not have any relation with the option saving – except when u deactivate and reactivate the plugin).
Also please let us know what version of PHP and wordpress you have installed.
I have a close to similar issue, am using WordPress 4.4 and pie-register version 2.0.21. The settings are ok but no verification emails are being sent. Am using multsite wordpress and initially thought it was the problem but I tried out with another site that’s not a multsite but it didn’t work. Emails with other plugins are working properly. Am using mysql version 5.5.45. Any assistance will be highly appreciated.