Race Against Time

Dr. Richard Koch remembers that first miracle baby like it was yesterday.

That was 30 years ago, back when Childrens Hospital of Los Angeles was a shiny, new monument to curvy ‘50s architecture.

Koch was chief of child development at the hospital and president of the Assn. for Retarded Citizens. A bill had just been signed by Gov. Pat Brown ordering hospitals to screen every California newborn for a disorder called phenylketonuria (PKU), a metabolic disease that eventually can cause mental retardation but that can be treated with a special no-protein diet.

The screening--in which newborns are pricked on the heel for a few drops of blood before leaving the hospital--put an abrupt end to a type of mental retardation that overtook about one in every 12,000 newborns (most often white) and was typically discovered only after parents would notice that little Susie, who looked perfectly fine at birth, wasn’t picking up her cup.

“We haven’t had a case of a baby institutionalized since then,” Koch says. “The program has been remarkably effective.”

But after decades of success, a disturbing twist has emerged in what has been one of medicine’s happier stories. It turns out that the first generation of PKU patients, now adults who are in their prime childbearing years, may still be at risk.

What’s more, the offspring of women with PKU are in danger of being born with mental retardation or other birth defects if the mother does not return to the special diet--which most adults discontinued years ago--before conception or early in pregnancy.

“You have 600 patients with normal intelligence [treated since 1966 in the California program] who are out in society,” Koch says. “Half of these people are women. We are very interested in finding these women.

“We have a tremendous potential for prevention here. One mentally retarded baby costs society $1 million.”

Only about one-third of these women have been located through California’s office for newborn screening or through hospital records, Koch says. Other states have had even worse luck locating PKU patients. In the meantime, it’s not known how many babies of PKU mothers are being born with preventable defects.

And that’s why Koch, at age 74, can’t force himself to retire.

*

“Yeah, my wife is upset about that,” he acknowledges one recent morning over cafe latte in the Childrens Hospital cafeteria. “But my patients keep me going, and these intriguing questions.”

With shaggy hair and rumpled casual clothes, Koch doesn’t wear the air of the distinguished doctor he is. A sportsman--he fishes, hikes, plays tennis and rides his bike almost two miles to work--Koch exudes the energy of someone 20 years younger. Zest--that word for older people who haven’t slowed down--fits him well.

He joined Childrens Hospital in 1951 as an intern. The hospital chief at the time had a keen interest in disabled children, many of whom were mentally retarded. He asked Koch to head a new child development unit that would be devoted to these children. He declined and entered a private pediatric practice.

“I was in a big office and was as busy as could be,” he says, tacking a chuckle onto the end of his words, as is his habit. “I decided maybe I had better go back and see what that child development position was all about.”

Koch has never looked back, carving a dramatic and important career in the burgeoning field of newborn screening.

“He says he is never going to retire,” says his wife of 52 years, Jean, with whom Koch has raised five children. “Even when we travel, it’s usually to medical meetings. We mix business with pleasure.”

The blend of business and pleasure is what Koch’s life is all about.

He decided to become a doctor 50 years ago while pondering his future inside a World War II German prison camp. One of nine children raised in a middle-class family in Petaluma, Koch had earned a scholarship to UC, Berkeley and later attended medical school at the University of Rochester in New York on the GI bill.

A bombardier during the war, Koch learned patience during his 18 months of captivity. And patience is among his greatest attributes now as he tries to resolve some of the remaining questions about PKU after three decades of work on the disorder.

Says Colleen Azen, the biostatistician on Koch’s research team: “Dr. Koch pretty much defines the field of PKU research.”

*

PKU is a metabolic disease in which a faulty gene allows too much of the amino acid phenylalanine--contained in many foods--to build up in the blood, causing brain damage. Avoiding phenylalanine in foods, mostly protein foods like milk and meat, keeps blood levels low enough to avoid damage.

While other scientists launched the PKU screening program, Koch leaves his mark on the field through his relentless desire to improve the lives of the first generation of babies treated with the diet; the miracle babies who could have been easily forgotten.

“Dr. Koch is really into the stuff that helps our generation,” says Christian Lutz, 28, a Granada Hills man who was found to have PKU in the early years of the screening program. “He’s a lifesaver. What can you say beyond that?”

Koch’s mission these days is to alert hundreds of adults with PKU that they--and the children of female patients--may be at risk for serious health problems if they have gone off the special no-phenylalanine diet.

Many PKU adults who have abandoned the diet may not know they are still at risk.

In the 1960s and ‘70s, PKU children were typically allowed to go off the diet (which is so restricted it makes Weight Watchers frozen meals taste like the best French gourmet food) between the ages of 6 and 10, Koch says. Many children were discharged from their doctors’ care to go off and eat hamburgers and French fries and live normal lives.

But in the late ‘70s and early ‘80s, health officials began to notice that the first generation of PKU women treated with the diet were having babies who were mentally retarded. These children did not have PKU; the disorder is the result of a defective gene that must be carried by both parents. Instead, these babies often had microcephaly, which features a small head and mental retardation. Some infants also suffered from intrauterine growth retardation, in which the baby fails to grow properly, and congenital heart defects.

It was clear that in PKU mothers who were on a regular diet, high blood levels of phenylalanine were causing damage to the fetus. The problem probably should have been foreseen, Koch says.

“Logically, we should have thought of it. But I think we were so enthused about these first PKU patients even being normal. That in itself was a shock,” he says.

The ability to so dramatically alter an individual’s fate had a powerful impact on the first group of doctors to apply the special PKU diet to newborns. Koch had seen mentally retarded PKU patients during medical school: “It left quite an impression on me.”

He even remembers the first baby he treated. It was 1965, the year before the state implemented newborn screening, and Childrens Hospital was already testing the process in a pilot program. Koch was handed a baby girl.

“She has done very well,” he says, noting that her IQ is normal. “But she went off the diet and I’m trying to get her back on. I’m worried for her future.”

He also worries incessantly about the babies of PKU mothers. Alarmed by the irony of a new generation of mentally retarded babies born to mothers who themselves had barely escaped mental retardation, Koch applied for grant money in the early ‘80s to study the problem. He wanted to test the theory that re-implementing the restricted diet before pregnancy or early in the pregnancy could protect the babies born to PKU mothers.

His request was refused--twice--before he received funding in 1984. Since then, Childrens Hospital has become the hub for 178 clinics nationwide that collect data on PKU patients. So far, Koch’s team at Childrens has been able to supply evidence that the sooner the pregnant woman begins the diet, the better the chances her baby will be born healthy.

Part of the study’s success was due to Koch’s coordination of the participating clinics. “It’s a testimony to his ability to bring together people from diverse disciplines and agree on a common goal,” says Eva Friedman, associate director of the Maternal PKU Collaborative Study. “He does not take offense easily or personalize criticism, but he enhances collaboration.”

As the study yielded evidence in the late ‘80s, a movement began to locate the first generation of female PKU patients and warn them about the risk to their babies. Even the American Public Health Assn. and the American Pediatrics Assn. issued statements a few years ago urging obstetricians to look for women at risk.

But the quest to find the oldest of the diet-treated PKU patients and attract them back into PKU clinics has not been easy.

Nowadays, the parents of baby girls born with PKU are taught about the importance of keeping their daughter on the diet and the implications if she becomes pregnant, says Dr. George Cunningham, chief of the genetic diseases section for the state’s Department of Health Services. His office dispatches newsletters to PKU families and even sponsors a PKU camp each summer for adolescent girls.

But women with PKU who move into California from elsewhere often escape the notice of the state health department. Others move and fail to leave forwarding addresses. Some mentally retarded adults with PKU, who were born before the screening program was implemented, are also giving birth without understanding the risk to their babies, Koch says.

“Some of the women, in moving about, get lost,” Cunningham acknowledges. “We have various ways of trying to track them. . . . But it is very hard to track people for any long period of time. This is an immensely mobile society. The phone numbers turn over every two or three years. The average address is for five years.”

In addition to their many attempts at finding PKU patients, Cunningham is trying to establish a program in which a short genetic screening questionnaire would be completed by every woman entering prenatal care. The questionnaire should tip off an obstetrician about genetic risk factors, such as PKU.

*

Robin Reimer is one of the rare PKU patients who wondered if her disorder might have an effect on the babies she hoped to have. Shortly after becoming engaged, she and her fiance sought genetic counseling.

It was the second time in her 31 years that Reimer has been in the right place at the right time. The first was in her own infancy.

Reimer was born in San Diego in 1965--the year before California began its newborn screening program. But instead of being among the last group of mentally retarded PKU patients, Reimer’s astute mother noticed that her newborn baby’s wet diapers smelled strange. She suspected there was something wrong with the baby’s urine and took her to the doctor.

“It just happened that this doctor took his chances and ordered a urine test for PKU. And it turned up positive,” says Reimer, who lives in Riverside. “It was a shot in the dark. Many doctors then didn’t even know about PKU screening.”

Reimer was put on a special formula and later, the restricted diet. Not as much was known about the treatment in the ‘60s, and there were far fewer foods manufactured especially for PKU patients. Parents were often advised to simply stop feeding the child after a certain amount of food intake daily.

“My mom said they wrote down detailed information on every bite that went into my mouth,” Reimer says. “Once I went over a set amount I got nothing but water. It was tough on my mom. She said there were many nights when I cried myself to sleep because I was so hungry, and she couldn’t give me anything else.”

Like many PKU patients in Southern California, Reimer was under Koch’s care at Childrens Hospital. As was standard practice at the time, she was allowed to go off the diet at age 9.

But while seeking genetic counseling a few years ago, she was told that she would have to resume the diet if she became pregnant. She did so and now has two healthy children, ages 2 and 3.

“They both were wonderful,” says Reimer, who is a preschool teacher. “But I have a good friend who has PKU and she didn’t know about the diet. Her baby had problems. And I know there are more women out there who don’t know they need to go back on the diet.”

To help locate adults with PKU, Reimer and Lutz have formed the state’s first support group for PKU adults. The mission of the group, called Adult PKU Connection, is to alert people of the importance of starting the diet again. The group will hold its first conference Oct. 20 in Tiburon, Calif.

“There has never been anything for PKU adults,” says Lutz, a college student and the father of two children. “The women have the PKU camp. But I feel the men, in particular, have been overlooked.”

Even male PKU patients or female PKU patients who are not contemplating pregnancy should consider restarting the diet, Koch says, because recent studies show that high phenylalanine levels in PKU patients who have the more serious forms of the genetic defect may cause continued neurological damage in adulthood; perhaps even a form of Alzheimer’s disease.

It is hard for adults who consider the diet a distant, horrible relic of their childhood to choose to go back on it, say Lutz and Reimer. Lutz went off the diet at age 6 but kept in touch with Koch. He often complained to Koch that he had difficulties in school and sometimes had trouble organizing his thoughts.

“Dr. Koch said, ‘You know, you should think about going back on the diet,’ ” Lutz recalls. “Then one day he called my wife and said, ‘You need to convince him to get back on the diet.’ I’m benefiting from the diet now. I can control my thoughts more. Everyone used to call me scatterbrained.”

Nowadays, tests can determine the severity of the genetic defect for each PKU patient, Koch says. That information helps determine how long an individual needs to stay on the diet.

“We keep many people on the diet indefinitely now,” Koch says. “Being on a diet that is so regimented is tiring and frustrating. These adults have to avoid almost all sources of protein, except special bread and milk substitutes that are prepared without phenylalanine. The diet costs $4,000 to $5,000 a year. One of my biggest problems is talking people into going back on the diet.”

“I think he is disappointed when they don’t stick to the diet,” says Jean Koch, who is also devoted to the PKU cause, having written a book about the history of newborn screening to be published next year. “But I think it’s also a challenge to him. . . . His patients like him because he takes a personal interest in them. He develops a real relationship with them. Some of them seem to view him as a father figure. They will call him when someone in the family goes to jail or for various reasons.”

And, as more PKU adults get the message about the importance of resuming the diet, the list of Koch’s admirers, some of whom have been his patients for more than 30 years, will surely grow.

“Dr. Koch was the match that lit my fire in getting the Adult PKU Connection going,” Lutz says. “Without him, I don’t know where I’d go.”

Adds Cunningham, himself an unsung champion of the newborn screening program: “All of the adults with PKU and the parents of PKU children may not have met Dr. Koch or recognize his name.

“But they owe him a debt of gratitude.”