Hi Helen,
"What's the trouble/problem with you?" is grammatically okay, although we don't usually say this. When we're showing concern, we're more likely to ask you:
"Are you all right?"
"What's the matter?"
"Is everything okay?"
"Is there something wrong?"
Usually, if "...with you" is attached to the end, it comes across as very patronizing:
"What's the matter with you?" can imply "Why is this even a problem? It shouldn't be!"
"Is there something wrong with you?" can imply "Do you have a problem that shouldn't be there?"
I hope this helps. Please let me know if you have any more questions.