That would depend on how the person meant it. What's up with you ? can mean what's new, how are you, etc. It can also mean that the person appears angry, upset, not themselves, so what's up with you ? means what's wrong ? what's bothering you ?

"What's up with you" is another way of saying "What is new in your life" or "Tell me what you have been doing recently". Just reply to it as you would these questions :)

Just in case, you don't know. I would add, that this is an informal way of talking and should only be used with friends.