The Possessed.(Lesch-Nyhan syndrome)

One day in September, 1962, a woman who here will be called Deborah Morlen showed up at the pediatric emergency room of the Johns Hopkins Hospital, in Baltimore, carrying her four-and-a-half-year-old son, Matthew. He was spastic, and couldn't walk or sit up; as an infant, he had been diagnosed as having cerebral palsy and developmental retardation. The emergency room was in the Harriet Lane Home for Invalid Children, an old brick building in the center of the Johns Hopkins complex, where a pediatric resident named Nancy Esterly saw Matthew. He had strange-colored urine, Mrs. Morlen told Esterly, "and there's sand in his diaper." Esterly removed the boy's diaper. It was stained a deep, bright orange, with a pink tinge. She touched the cloth and felt grit. She had no idea what this was, except that the pink looked like blood. She learned from Mrs. Morlen that Matthew had an older brother, Harold, who was also spastic and retarded. Harold was living at the Rosewood State Hospital, an institution for disabled children, outside Baltimore, while Matthew lived at home.

Since both brothers seemed to have the same condition, Esterly thought it likely that they had a genetic disease, but, if so, it wasn't one that she'd ever seen or heard of. Esterly also noted that Matthew was wearing mittens, even though it was a warm day. She admitted the little boy to the hospital.

Esterly took a sample of Matthew's urine, and both she and an intern looked at it under a microscope. They saw that it was filled with crystals. They were beautiful--they were as clear as glass, and they looked like bundles of needles, or like fireworks going off. They were sharp, and it was clear that they were tearing up the boy's urinary tract, causing bleeding. Esterly and the intern pored over photographs of crystals in a medical textbook. The intern asked if the crystals might be uric acid, a waste product excreted by the kidneys; however, cystine, an amino acid that can form kidney stones, seemed the most likely candidate. Esterly needed a confirmation of that diagnosis, so she carried the sample upstairs to the top floor, where William L. Nyhan, a pediatrician and research scientist, had a laboratory. "Bill Nyhan was the guru of metabolism," Esterly told me.

Nyhan, who was then in his thirties, had been studying how cancer cells metabolized amino acids, in an attempt to find ways to cure cancer in children. "It was one of my impossible projects," he said to me recently. Nyhan is now a professor of pediatrics at the University of California San Diego School of Medicine. "I love working with kids, but dealing with pediatric cancer was depressing, saddening, and, in truth, maddening," he said. Nyhan ran some tests on Matthew's urine, using equipment he had designed. The crystals weren't cystine, or any sort of amino acid. They proved to be uric acid. A high concentration of uric acid in a person's blood can lead to gout, a painful disease in which crystals grow in the joints and extremities, particularly in the big toe. Gout has been known since the time of Hippocrates, and it occurs mainly in older men. Yet the patient here was a little boy. Nyhan had a medical student named Michael Lesch working in his lab, and together they went downstairs.

Matthew lay in a bed in an open ward on the second floor of the Harriet Lane Home. He was a spot of energy in the ward, a bright-eyed child with a body that seemed out of control. The staff had tied his arms and legs to the bedframe with strips of white cloth, to keep him from thrashing, and they had wrapped his hands in many layers of gauze; they looked like white clubs. Nurses hovered around the boy. "He knew I was a doctor and he knew where he was. He was alert," Nyhan says. Matthew greeted Lesch and Nyhan in a friendly way, but his speech was almost unintelligible: he had dysarthria, an inability to control the muscles that make speech. They noticed scarring and fresh cuts around his mouth.

They inspected Matthew's feet. No sign of gout. Then the boy's arms and legs were freed, and Lesch and Nyhan saw a complex pattern of stiff and involuntary movements, a condition called dystonia. Nyhan had the gauze unwrapped from the boy's hands.

Matthew looked frightened. He asked Nyhan to stop, and then he began crying. When the last layer was removed, they saw that the tips of several of the boy's fingers were missing. Matthew started screaming, and thrust his hands toward his mouth. With a sense of shock, Nyhan realized that the boy had bitten off parts of his fingers. He also seemed to have bitten off parts of his lips.