1. Symptoms

“I don’t think he had a heart attack,” the patient’s wife declared emphatically. “I don’t care what the doctor in the hospital said.” The patient nodded his agreement. “But we need to be sure,” she added in a distinctive Long Island accent. That’s why they had gone to see Dr. Bruce Decter in New Hyde Park, N.Y., a cardiologist just out of training — to get a second opinion from someone a little closer to the books. The patient, a lanky 42-year-old man with a chiseled jaw, retreating hairline and skinny ponytail, seemed tired and anxious and grateful to have his childhood sweetheart do all the talking.

He had chest pain off and on for most of his adult life. His internist didn’t think it was his heart, and a normal stress test done the previous year seemed to confirm that. Then the week before his visit to Decter, his chest began to hurt while making love. It spread to his left shoulder and arm. And it didn’t go away. He hardly slept at all that night because of the pain and a gnawing anxiety that this time it really was a heart attack.

First thing the next morning he went to his internist. An EKG was normal, but the patient was so worried that his doctor arranged for him to see a cardiologist that afternoon. By then the patient was pale, sweaty and shaking. “I think you’re having a heart attack,” the cardiologist told the patient and then sent him straight to the E.R. The EKG done in the hospital was normal, but a series of blood tests indicated that he was having a heart attack, and a big one. He was rushed to the cardiac catheterization lab to see if the clogged vessel could be reopened. To the doctors’ utter amazement, there was no blockage; his heart looked fine.

Still, the cardiologist was certain that the patient had some kind of heart problem. As he explained it, there was either a blockage that reopened on its own, or he had a spasm in one of the coronary arteries. In either case, the patient was lucky that his heart hadn’t been permanently damaged. The cardiologist started the patient on a beta blocker — a medication that has been shown to protect the heart. But the chest pain kept coming.

2. Investigation

At his office, a week after the trip to the E.R., Decter examined the patient, a fit middle-aged man. His blood pressure was perfect. His heart rate was regular and slow. In fact, his entire exam was completely normal. He got another EKG. Also normal. The patient’s blood tests from the E.R. seemed to indicate that he had had a heart attack, but none of the EKGs or the angiogram revealed any abnormality.

The problem for Decter was one that doctors face regularly: how to reconcile tests that contradict one another. Often patients, and even doctors, think that test results provide a definitive answer — like the solution in today’s paper to yesterday’s crossword. But every test carries a risk of being wrong, and all tests need to be interpreted. This is never clearer than when different tests seem to tell different stories. Could these apparently contradictory results be shaped into a single narrative that made sense?

The blood test in question measures an enzyme that is released when a muscle like the heart is injured. That enzyme, creatine phosphokinase, abbreviated as CPK, was normal when the patient first presented to the emergency room but rose to a level 20 times higher than normal over the next several hours. In a patient who has chest pain that comes on with exertion, an elevated CPK usually means that the patient is having a heart attack.

But damage to any muscle will cause CPK to increase, so there is an additional test that can determine whether the enzymes are leaked from a damaged heart or from damaged skeletal muscle. When Decter called the lab for results of this test, he found that the CPK hadn’t come from the heart; it had come from the muscles of the arms and legs. “You’re right,” Decter told the anxious patient. “You didn’t have a heart attack.” But at this point, the young cardiologist acknowledged, he wasn’t at all sure what the patient did have.

The patient considered himself pretty healthy, he told the doctor. He took no medicine, had never smoked and exercised daily. In fact, the only other time he’d ever been in the hospital was when he was 21 and had mononucleosis. His urine then was really dark — “the color of Coca-Cola” — and the doctors were worried.

When Decter heard that, something stirred in his memory. Cola-colored urine. Perhaps this was the key. Had he had this kind of dark urine since then? he asked. The patient told him that a couple of times a month his urine would turn brown and he’d feel achy all over. It happened whenever he was sick or tired or when he exercised too hard. He’d told lots of doctors about it, but none of them could figure out what was going on.

Decter knew he was on to something. Urine that dark is usually caused by muscle breakdown. When muscle cells are damaged, they leak CPK, but they also spill several other chemicals. One of them, the compound that gives skeletal muscle its distinctive deep red hue, can turn urine a dark brown. Were the brown urine and the elevated CPK caused by the same problem? Were they both signs of some longstanding disease process that was destroying this patient’s muscle?

Decter sent his patient to Dr. Alfred E. Slonim, a pediatric endocrinologist by training who spent his career investigating diseases of the muscle. The patient called Decter after seeing the specialist, almost speechless with excitement. Slonim spent more than an hour with him and his wife, getting the history of his strange illness. “Tell him about what happens on Yom Kippur,” his wife prompted near the end of the interview. Every year on the Jewish day of atonement, the patient would fast for a day, from sunset to sunset. And every year, he would spend the day after Yom Kippur in bed, crippled by an aching in his muscles and passing dark brown urine. Once he said that, Slonim had the diagnosis: the patient had a form of the genetic disease known as carnitine palmitoyltransferase deficiency or CPT.

3. Resolution

In this rare genetic disease, patients are missing the necessary biological equipment to burn fat for energy. Normally the body uses a type of sugar provided by the diet or stored in the liver to keep the body running. When that sugar is used up, the body switches to fat for fuel. Patients with CPT can’t do that. Instead, when they run out of sugar, their bodies are forced to turn to the second backup form of energy: muscle. When this patient’s body depleted the normal fuel — because of decreased intake (fasting or illness) or increased metabolic activity (exercise or fever) — it had to turn to the energy stored in muscle just to keep the biological motor running.

This diagnosis finally allowed the patient and Decter to make sense of the original story. The CPT gave the patient terrible, chronic heartburn; the delicate tissue of the esophagus, when injured, can cause a pain that feels to many patients very much like the classic presentation of a heart attack. Certainly this patient thought he was having one the night he had sex. He didn’t sleep and didn’t eat all the next day when he was in the E.R., and that is what triggered the attack on his muscles and elevated his CPK numbers. “It’s incredible that it took a wrong diagnosis to get to the right one,” the patient told me. There’s no cure for this disease, but frequent meals can help ward off many attacks.

As for Decter, he says he doesn’t believe that this disease is quite as rare as he was told in medical school. Over the past decade, he has seen four patients with unexplained elevations in their CPKs and no evidence of heart disease. Two have tested positive for CPT-like genetic disorders. He’s still trying to figure out the other two.