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.