I've also been affected by this issue. Following the gpg-agent troubleshooting instructions in https://enigmail.net/index.php/en/faq-en?view=topic&id=14 helped, however, it took me quite a while to find out where the issue originated from. A better error message would have been very helpful. My setup was such that I've been using a console based pinentry program which (obviously) can't work with enigmail. I've attached a debug log which shows the problem (I've replaced most key ids and mail addresses...
Default completion shortcuts collide with OS X system shortcuts
Disabled shortcuts not properly disabled at startup
Should be in OSX Settings > Keyboard > Keyboard > Use F1,... as function keys (not...
Did you try pressing Fn+F5? Just pressing F5 is probably interpreted as multimedia...
Wrong TIM1/8_CLK on STM32F30x when using PCLK2 with prescaler
Target configurations only set cortex_m reset_config for first target