February 26, 1999

Pioneering procedure eases child’s rare blood disorder

Pioneering procedure eases child's rare blood disorder

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During a recent clinic visit, three-month-old Ashley Cody was the center of attention for Dr. Marshall Summar (holding Ashley) and Nurse Susan Slyke (second from right) as well as her parents, Jennifer and Mark. (Photo by Donna Jones Bailey)

As you watch three-month-old Ashley Cody's bright blue eyes meet her father's adoring gaze, it is difficult to imagine how close to dying the infant came during her first days of life.

A rare, inherited metabolic disorder caused ammonia to build up in the girl's blood to levels that sent her into a coma and pushed her to the brink of death. Quick action by caregivers in the neonatal intensive care nursery at the Chattanooga hospital where she was born brought the baby to Vanderbilt Children's Hospital, where she became only the fourth newborn in four years to undergo a pioneering technique to quickly strip the ammonia from her blood.

Ashley's mother, Jennifer, says she wants to help educate other parents about the disorder's subtle initial symptoms in the hopes of preventing tragedies like the one her family barely escaped.

"I'm just so afraid that we're not the only ones, that these kids are going home from the hospital and dying," Jennifer said during a follow-up visit in the VCH Outpatient Center.

Ashley was born with a rare genetic defect that interferes with the urea cycle, the biochemical pathway that converts waste nitrogen to urea for excretion in the urine. Nitrogen is the by-product of the breakdown of protein and travels in the bloodstream as ammonia, which at high levels is toxic to a number organs, especially the brain.

"The brain starts to swell, and the babies eventually go into a coma," said Dr. Marshall L. Summar, associate professor of Pediatrics. "As the babies become more and more lethargic, they eat less and less, so their body begins to break down their own protein for energy, which produces more nitrogen/ammonia, and a vicious cycle sets in. These children get into a downward spiral very fast and can die quickly."

Summar and his colleagues are among very few scientists around the world whose work focuses on the urea cycle. The VCH group is the only one studying the gene that controls the cycle, while other researchers focus on other steps in the process.

Jennifer's fear for other families is not unfounded, Summar said. Because the condition is rare ‹ occurring in only an estimated one in 20,000 births ‹ and because it begins subtly but escalates rapidly, an unknown proportion of deaths attributed to Sudden Infant Death Syndrome could be linked to urea cycle defects.

"If a newborn becomes lethargic, parents should consult their pediatrician," he said.

Ashley, Jennifer and Mark Cody's first child, was born at 37 weeks' gestation ‹ virtually full-term ‹ with no apparent complications. However, by two days of age, she had developed jaundice, had become lethargic and wasn't eating, her mother recalls. The caregivers at the Chattanooga hospital told the Codys that they suspected that Jennifer's due date had been slightly miscalculated and that Ashley was slightly premature. But on the third day, Ashley went into a seizure and stopped breathing.

"We had just returned to the nursery from packing some clothes for her, and we saw them rushing a baby to the NICU," Jennifer recalls tearfully. "I said, 'Oh, that is such a sick baby,' only to find out that it was my baby."

After a barrage of other tests, the caregivers in Chattanooga "astutely" decided to measure Ashley's ammonia levels, Summar says. Her level was over 1,200 micromoles per liter, compared to a normal level of 35. "A level of 100-200 would put most adults into a coma," Summar said.

Weather that day prohibited bringing the baby to VCH by air, so she was rushed to Nashville by ambulance.

The traditional approach would be peritoneal dialysis ‹ which filters wastes from the blood inside the abdominal cavity ‹ and would take at least four or five days. During that time, Ashley's brain and other organs would continue to be damaged by the excess ammonia in her blood.

Only four years ago, pediatric surgeon Dr. John B. Piestch, associate professor of Pediatric Surgery and Pediatrics, Summar, and a diverse team pioneered a technique to strip the ammonia from the bloodstream much more quickly. Because urea cycle disorders so rarely occur, the innovative technique has only been used four times since.

Piestch inserted an intravenous catheter into Ashley's neck and connected it to the ECMO (extra-corporeal membrane oxygenation) machine typically used to bypass ill newborns' lungs. The ECMO machine was then connected to a dialysis machine to filter the ammonia from the blood before returning it to Ashley's body. The extra pressure provided by the ECMO machine is used to drive the dialysis unit very quickly, allowing the ammonia to be filtered from the blood in a matter of hours rather than days.

"We were able to bring Ashley's blood levels of ammonia down to a safe range within about an hour," Summar said. "We really hit this from every direction. In addition to the dialysis, we use drugs that act as ammonia-scavengers to remove ammonia. Because we are not using the gut for dialysis, we can start a naso-gastric drip of formula into the stomach to provide calories so the child's body stops breaking down its own protein."

After about two weeks at VCH to regulate her feedings and otherwise stabilize her, Ashley returned to Chattanooga. Like other children with urea cycle defects, she faces years of strict medical and dietary management, including a strictly regimented low-protein, high-calorie diet.

But Summar and his colleagues hope they have gotten Ashley over the biggest hurdle, which for most children with urea cycle disorders is the first few days after birth.

"If we can improve the odds during that period, there will be other therapeutic options later on, including medical management, liver transplant, and we hope in the not-too-distant future, gene therapy," Summar said.

"This technique requires that a large and diverse group come together, including pediatric surgeons, nephrologists, dialysis nurses, intensivists, the metabolic disease team, pharmacy – everything has to work together for this to happen. There are very few places where it comes together this well."