Sixteen-year old chess prodigy Nate Harrison easily mows down an older opponent while mocking his moves. Afterwards, the opponent offers Nate a handshake and congratulations. Nate winces and begins breathing rapidly. He picks up the chess clock and smashes it in his opponent's face. Nate jumps on the man, pounding him with punches until proctors are able to drag him away. Nate holds his head in agony, fighting for breath.
As Chase examines Nate in the hospital, the boy's mother Enid stands at his bedside. Nate is sarcastic and difficult to him. Chase ignore his jibes and presses on with the exam. Chase presents the case to the team. He says that the boy is dealing with rage and head pain, plus various bumps and bruises from the seventeen fights he's been in this semester alone. House adds "personality disorder" to the list of symptoms. Suspecting that the diagnosis is cluster headaches, House asks them to start Nate on blood thinners and he prescribes Transcranial Magnetic Stimulation.
Foreman performs the procedure on Nate, who continues to be obnoxious. Outside, Chase explains to Enid that cluster headaches often cause irritability or hostility. If they are right about the prognosis, then treatments could change Nate. This delights Enid. She had thoughts that she was a bad mother because she hated Nate.
The next morning, the team explains to House that the blood thinners and TMS had no effect. They rule out cluster headaches and now suspect hemochromatosis or hypothyroidism. House quickly shoots down both conditions because they don't match Nate's personality issues. House sticks with cluster headaches, arguing that symptoms never lie. Cameron points out that the only approved treatment left is brain surgery, which is not a guarantee. House smiles, noting that they will be forced to use an unapproved treatment.
When the meeting ends, Foreman storms out. He tells House that he had an interview lined up for the day before at New York Mercy Hospital, but they said he cancelled. Yet he never called them. Foreman accuses House of going behind his back and questions whether he has a neurological issue. House claims innocence, coldly explaining that he only sabotages people he deems worth the trouble.
House congratulates Cuddy on her cunning move of canceling Foreman's interview. Cuddy firmly informs him that it wasn't her but that she is awaiting board approval to make Foreman an offer to stay. House asks permission to give Nate mushrooms to treat his cluster headaches because the psilocybins in them work on the headaches. Cuddy only permits a low dosage of less than ten milligrams given in a tightly controlled setting. House also must obtain parental approval.
Chase and Cameron administer the drugs and then observe Nate. He is not feeling any pain in his head but rather the opposite. Cameron says that this confirms a diagnosis of cluster headaches. Nate then invites Cameron to have sex with him and he lifts up his blanket. The doctors see that his testes are undersized but that his other sexual characteristics are normal. They turn their focus to the hypothalamus. House orders Chase and Cameron to biopsy the pituitary.
Enid is all for the procedure but Nate refuses to have his brain cut open. Suddenly, Nate becomes disoriented and blacks out. Chase notices that his gums are yellow and realizes that Nate is jaundiced. The liver is shutting down. Chase and Cameron start the patient on sodium polystyrene sulfonate.
The boy's liver is operating at around twenty percent and deteriorating fast. It's possible that the liver failure caused the other symptoms, but what caused the liver failure? Foreman gets a page. House assumes it's from Cuddy and excuses Foreman to handle his business. Chase mentions that Nate was raised a vegetarian but then started eating meat a few months ago. House observes that, with an OTC deficiency, Nate wouldn't be able to metabolize the nitrogen and this would damage the liver. He orders the doctors to stuff Nate full of meat and wait for his ammonia levels to spike.
Cuddy presents Foreman with a deal to double his salary and put him in charge of his own diagnostic group. He would work parallel to House but have complete autonomy. Foreman thinks about it and then quickly declines. Since somebody at the hospital sabotaged his interview, he can no longer work there.
Chase and Cameron bring Nate a giant platter of hamburger patties. He demands a higher quality meat and won't eat them. Chase snaps. He threatens to strap Nate down and force the meat into his system. Nate backs down and takes a bite.
Cuddy accuses Wilson of killing Foreman's interview in order to help House. Wilson says he hopes Foreman will leave so that House realizes he needs another doctor to stand up to him. Cuddy doesn't believe him, labeling Wilson an enabler. Wilson calls Cuddy paranoid.
The hamburger test shows no change in Nate's enzyme levels, meaning he is not affected by OTC deficiency. House's next idea is to starve the boy because diabetic steatosis will screw up the liver, which will allow them to see if the blood sugar pops. Chase warns that messing with Nate's blood sugar could set off another rage.
The changes do cause Nate to rage, and the doctors find him jaundiced in his room. Nate is swinging around his IV pole and threatening the nurse and his mother to feed him. The doctors tell Nate that once they get a urine sample he can eat. Nate defiantly pees on the floor. Yet his urine changes from bright yellow to blood red.
A chem panel confirms that the bloody urine is due to kidney failure. Nate is put on dialysis, which he will need for the rest of his life. Now the team is stuck for answers. Foreman throws out hepatic fibrosis or MCADD. Considering that it might be a genetic disorder, House asks them to acquire the sequencing primers and figure out if it's one of the genetic diseases they can actually fix. Foreman announces that he has to leave and House questions if he's going to a job interview. Foreman wants to know whether House will stop him if it is.
Wilson tries to get Cameron to believe Cuddy is going to fire him for sabotaging Foreman's interview but she sees right through his weak attempt. Wilson becomes annoyed, noting that she would have fallen for this three years ago. Cameron asks whether he thinks she was the culprit, but she denies it. Cameron finds Chase in the lab and asks if he did it because he wanted to sabotage Foreman. Chase is stunned that she would consider him to be that petty.
The genetic lab tests show that Nate has a partial HPRT enzyme deficiency, which means he could have Kelley-Seegmiller syndrome. Yet since it's partial, he might not have it. Cameron argues that patients with this syndrome self-mutilate, and Nate hasn't been chewing his lips or banging his head. Chase points out that self-mutilation only happens when the patient is stressed. House wants to stress Nate to the breaking point in order to receive their confirmation.
House walks into Nate's room with a chessboard and immediately starts mocking him for not wanting to play. This gets Nate riled up. As the game progresses, Nate is surprised that House is a good match for him. House begins taunting Nate, pointing out that nobody likes him. House tells Nate that he's dying and then takes the boy's knight with his queen, which puts Nate in check. Nate's breathing quickens, but then he moves his bishop and smiles. He asks House if he wants to lay down his king, explaining the next four moves that will put House in checkmate. Looking at the board, House realizes that Nate is right. Yet the greater surprise is that Nate is starting to convulse with a seizure.
The next day, House is studying a chessboard and announces to the team that he hates Nate. The team despairs, realizing that they have one more symptom and one less explanation. Chase asks if Nate took any medication and lied about it. This sparks an idea in House. He crosses personality disorder off of the whiteboard and declares that now they are dealing with a normal jerk who suffers from amyloidosis. House tells the team to flush Nate with immunosuppressants, perform a biopsy to confirm and find a bone marrow donor.
The biopsy, however, comes back clean with no signs of amyloidosis. Yet House isn't deterred, and tells Foreman to biopsy the sinuses for a different reading. Foreman resists, but House says that he can either argue about it and then do it or just do it. Foreman shrugs and walks away. House shouts after him that he wasn't finished. The third option was to not do what House asked. He could have stuck Nate on antibiotics but he didn't because he still trusts House's judgment more than his own.
Chase finds House in his office that night. He knows House was the one who sank Foreman's interview. Everybody has been chasing ghosts over this, so either nobody did it or somebody wants everybody chasing ghosts. He thinks this sounds like House's doing. House smiles, admitting that sometimes he forgets why he hired Chase. If House wants Foreman to stay, Chase advises him to just simply tell him. At least it will make Foreman see that House isn't evil. This idea gives House an epiphany about Nate's case. When they crossed off personality disorder, they forgot to add another symptom.
House strolls into Nate's room holding two chess pieces and asks if he wants white or black. Nate grabs for a piece and House notices that he keeps his thumb straight when grabbing objects. House bends the thumb backwards and Nate yelps in pain. He cannot bend his thumb because the bones have formed abnormally due to the junk that has pushed its way between them.
Nate has hemochromatosis, and his body is absorbing iron from his food but he can't process it. The iron is building up in the organs and joints, creating havoc. As for the personality disorder, House points out that Nate is simply a jerk and that this has nothing to do with the iron. House pulls out the IVs and pokes Nate's wrist with a scalpel. He calls in a nurse, instructing her to stop the bleeding when three pints have dripped into the garbage can. Nate will need dialysis and a blood drain about every three months for the rest of his life. Other that that, he will be fine.
House finds Foreman in the lab and asks whether he is still running the biopsy for amyloidosis. House has Foreman run it again to recheck his results, and warns him that he will probably have an all-nighter in front of him.