I think "What is it with them?" should be an answer too. At least in my head it would mean pretty much the same as "What is up with them?".
I agree with EeroK that "what is it with them?" should be accepted as an answer. If it is grammatically uncorrect or is not a correct translation then other pages should be altered because "was ist mit ..." is translated and accepted correctly on other pages as "what is it with ..."
Well . . . it doesn't really mean the same thing in English. "What about them?" is neutral--e.g., "Are they coming too?" "What's with them?" implies there's something wrong, or at least weird, with the way they are acting. But the important question is--what does the German expression mean, exactly?