The young man's mother said, "He gets like this."
"Like what?" I asked.
"Pain. He gets this pain in his stomach, and then he gets like this."
She was a country woman, shy with doctors. She wouldn't look at me as she told her son's history. He was 22 and clearly in pain. From the moment he stepped into room 7, I could hear him wailing and moaning.
The problem was that somehow it just didn't seem real. While the nurse was trying to start an IV, he lay there acting as if he were being nailed to a cross: "They're killing me."
The nurse's note was to the point: "History of abdominal pain, now with same, only worse." I laid my hands on the young man's abdomen and wasn't surprised it was soft. Nothing there.
I continued the exam, his mother regarding us both. "He gets real constipated," she said, "and then he gets strange in the head. Sometimes he doesn't make a lick of sense." She searched for a moment and then found the correct word. "Peculiar." She looked as if she had had about enough.
"How long has he had this pain?"
"Oh, couple a years. Off and on."
"Has he seen a doctor about it?"
"He's seen pret' near every doctor and they say pret' near the same thing: Don't know."
Chronic belly pain is a vast wasteland of diagnostic dead ends. Test after test can send a physician back to the beginning. Even the best of them often come up with nothing more definitive than dyspepsia, Latin for "bad digestion."
"Your son ever seen a psychiatrist?"
"He's seen a couple..."
"What did they say was wrong?"
"Well, they said different things. One doctor said he was depressed, and another doctor said he had an anxiety problem. And one doctor just told me his problem is all in his head."
I noticed something that didn't fit. Sweat was beading on the man's forehead and upper lip. If you're just looking for attention, that's hard to fake.
Sometimes when I am stumped for a diagnosis, I try to simplify as much as possible. How would I describe this case in a few words? Well, it would be belly pain and craziness. Delirium would be the medical word. So what would cause belly pain and delirium?
I had the image suddenly of a man running down the hallway in his white nightshirt, raving like a madman—King George III of England. Porphyria. The king had porphyria.
Porphyria is a family of diseases, rare diseases, several of which manifest as gastric symptoms and mental-status changes. Some historians think King George, who would dash naked down the castle halls while his ministers and advisers chased frantically after him, was a victim of porphyria.
I tried to remember what you do if you suspect porphyria. This is not a disease emergency room doctors diagnose every day, except in South Africa, where, because of a genetic fluke, it's common in the Afrikaner population. I looked at the young man and wondered if he could be of Dutch descent.
"Does his urine ever get dark?" I asked the mother.
The mother drew back. "Well," she said, "I don't know. He drinks a lot of pop."
I had seen a urine specimen from him. I found it, still waiting to be tested, by the vacuum tube.
I remembered that before you diagnose porphyria, you must test the urine. But test it for what? Pigments, I remembered; you test for pigments. Pigments are molecules that love light. With that in mind I held the patient's urine up to the light to examine it.
I saw a weird color, a brilliant burgundy, oxblood red. More telling was a faint strip of deep-water blue up near the surface.
Porphyria comes from the Greek word for purple. All porphyrins are pigments. They function as energy transporters in many systems and are also involved in the assembly of the oxygen-transporting component of hemoglobin, the heme, in our blood.
For most people, this system works just fine. Occasionally, though, one of the enzymes involved in making heme molecules is defective or disabled. In that case half-baked, not-quite-heme molecules pile up. Porphyrin molecules and their precursors begin to spill into the bloodstream and out through the kidneys into the urine. Eventually, the cells that manufacture heme begin to malfunction, and biological chaos ensues. The result: symptoms of porphyria.
By some whim of nature, the organs primarily affected by the disease are not the liver or bone marrow cells but the nervous system and the skin. With skin involvement, just a brief stroll in the bright sun produces major skin injury. Nervous system involvement produces sensory changes, paralysis, madness. Abdominal pain is a common symptom, but the abdominal organs aren't directly involved. The symptoms come from madly misfiring neurons that activate the pain receptors lining the abdominal cavity.
King George III of England suffered from intermittent bouts of madness, now thought by some to be secondary to porphyria. He developed his first episode when he was in his twenties. They were classic: abdominal pain with severe constipation and delirium. His doctors were baffled both by his symptoms and by the results of one of the few tests they could do: a detailed inspection of the king's urine. In times of madness, they wrote, his urine was "sometimes wine dark and sometimes deep blue." We now know this was the shimmery blue of dissolved porphyrins.
The king went mad, recovered, lost an empire, went mad again, recovered, and finally died mad, leaving behind the mystery of his blue urine.
I thumbed through an old textbook to find what diagnostic tests I should order: 5-Aminolevulinic acid, ALA for short, and porphobilinogen.
I ordered the tests. Then I did what people in the emergency room always do when a strange case like this comes up: I forgot all about it. Other dramatic cases showed up. There was a sexually abused 10-year-old girl and a baby born in the ER parking lot.
I would never have known this patient's diagnosis if I hadn't called his doctor a week later about a different patient.
It was early in the morning, and I had called to admit an asthmatic patient. The doctor asked me sleepily, "Do you remember that patient... that kid you admitted last week? Well, you were right. The kid has porphyria. Somebody should have picked it up long ago." He said the patient might be able to control the symptoms through changes in diet. But porphyria comes in several varieties, he added, and the young man's treatment would depend on what type he had.
Driving home that morning, inching along in rush-hour traffic, I had a vivid vision of myself. I was a giving a lecture on porphyria, presenting my patient to an audience and explaining the biochemistry of porphyria. I was going through the metabolic pathways of heme synthesis, using a diagram detailing the steps in porphyrin's synthesis. I was explaining all this and knew I was doing a great job. When I turned around to address the audience, though, I found it was not made up of doctors but of patients—all with belly pain. Everyone looked sick and worried. Everyone was pointing to his or her own abdomen. Then each said the same thing in one unified voice: "OK, OK, so you diagnosed a case of porphyria. But what I want to know is, What about me? What's my diagnosis?"
That's when I realized I hadn't a clue.
