After some debugging, it looks like the problem is a known issue with USB serials under wine. It looks like one (or both) of two things.
A The driver for the Prolific PL2303 (which my Holux uses) doesn't support the TIOCGICOUNT ioctl (has a *TODO* in the driver)
B. fixme:comm:set_queue_size insize 1024 outsize 256 unimplemented stub in wine. Another todo.
I'm tempted to get a serial GPS to test it as I actually have a real serial port. Other than that, it seems to work great. I don't care for the voice so much as it doesn't really do anything except say the street name.