ESCONDIDO — At the age of 6, Christina Hale has yet to eat her first full meal. Since birth, her nourishment has come in the form of a chalky-white liquid delivered through a plastic tube that runs into her nostril and down her esophagus.
It is a sacrifice that she and her parents are very willing to make. Without the carefully calibrated liquid diet and feeding regimen developed at a special research center at UC San Diego Medical Center in Hillcrest, Christina probably would not be alive.
Christina is a victim of methylmalonic acidemia, a rare disorder that usually kills children who lack the enzyme needed to break down methylmalonic acid, a byproduct of protein metabolism. The substance accumulates in their tissues soon after birth, causing coma and, ultimately, death.
As one of the oldest living persons with the disease, Christina is an example of the progress made under a new therapy developed by a UCSD physician and the value of the precise skills in use at the hospital's specialized "metabolic kitchen."
It is there that researchers and nutritionists test Christina and children with other metabolic disorders to devise dietary regimens critical to their health and to advance medical knowledge of these kinds of diseases. In Christina's case, for example, there is no known medical treatment. Her diet is, quite simply, all that keeps her disease in check.
"She is an example of the success of this program," said Dr. Orville Kolterman, program director of the General Clinical Research Center, which includes the kitchen. "Ten or 15 years ago, those children had a miserable existence, and they almost uniformly died. And the ones that didn't die were severely growth retarded because of the severely restricted diets they felt they had to be on to survive."
The $1.8-million research center includes an eight-bed ward, 12 specially trained nurses, an outpatient facility at the UCSD medical school in La Jolla and a small laboratory. The center is one of 78 across the nation funded by the National Institutes of Health.
Its mission is diagnostic and therapeutic research in nutrition, metabolic diseases, oncology, reproductive medicine, hypertension and diabetes, Kolterman said. Patients like Christina are treated as part of ongoing research into metabolic diseases. For example, Christina's physicians have published five papers based on research conducted with Christina.
Knowing What's Eaten
Other faculty members at UCSD have access to the research center and the metabolic kitchen. A university psychiatrist is studying a possible link between sodium in diets and levels of stress and anger. The research is using some transients as subjects, which has the added value of giving them a warm bed and good food for a few nights while they are in the hospital.
Kolterman is seeking subjects for participation in a nationwide 10-year study to determine whether a tightly controlled diet and various insulin regimens can slow the progress of diabetic retinopathy, which leads to blindness in diabetics.
Still other researchers are using extremely high-fat diets to control seizures and malnutrition among girls with Rett syndrome, a recently discovered and little-understood disorder.
"There are many investigations that require patients to be on very specifically defined diets," Kolterman said. "It's important for the researcher to know exactly what the patient is eating."
Christina's disease is a perfect example. The problem facing her and her doctors is this: Because of the missing enzyme, her system does not break down methylmalonic acid when metabolizing four specific amino acids contained in protein. But because the amino acids are essential for life, she must consume them to grow.
The treatment is to give her just enough protein to sustain growth, but not enough to make her ill.
"If you don't give her enough, you're in trouble from that direction, and the minute you give too much you're in trouble," said Dr. William Nyhan, Christina's physician and a world-renowned specialist in metabolic disorders. "So you have to walk a very difficult tightrope."
How precise must the measurements be? According to Nancy Stubblefield, a research associate at the kitchen, a difference of five grams of protein over a period of time could make a grave difference. That is about the amount of protein found in one ounce of meat.
"Let's say her requirement is 20 to 25 grams of protein per day," Stubblefield said. "If she got to 30, or even to 26 or 27, and consistently had that day after day, she would probably get sick. You're talking about a five-gram difference, and that's not much when it comes to food."
Instead of solid food taken by mouth, Christina lives on the complicated formula of nutrients and water devised by researchers and nutritionists in the metabolic kitchen. Her mother has been taught how to mix up the recipe, which is "like baking a cake every morning," Stubblefield said.