Check for the availability of a typedef by using the CheckType method:

env = Environment()
conf = Configure(env)
if not conf.CheckType('off_t'):
    print('Did not find off_t typedef, assuming int')
    conf.env.Append(CCFLAGS='-Doff_t=int')
env = conf.Finish()
    

You can also add a string that will be placed at the beginning of the test file that will be used to check for the typedef. This provide a way to specify files that must be included to find the typedef:

env = Environment()
conf = Configure(env)
if not conf.CheckType('off_t', '#include <sys/types.h>\n'):
    print('Did not find off_t typedef, assuming int')
    conf.env.Append(CCFLAGS='-Doff_t=int')
env = conf.Finish()