Twenty-Five Years of PKU: Looking Back
by Virginia Schuett, Editor, National PKU News
Many subscribers to National PKU News have asked me how I got involved with PKU. Here is the story, reprinted from the Spring/Summer 1997 issue of the newsletter.
I am still trying to fathom that twenty-five years of my life have been inextricably connected to PKU. Maybe it is easier to appreciate when I realize I can no longer remember the feeling of not having this connection. I have to admit, my PKU involvement is a strong part of my identity and has been a prominent force in shaping my adult life. It is a niche that somehow has worked wonderfully for me, melding with my personality, challenging my strengths, fulfilling my need to do something unique, rewarding and worthwhile.
How did it all start? One sunny day in June, 1972, I walked through the doors of a PKU clinic in Madison, Wisconsin. I was a naive young college graduate with a Master’s degree in nutrition, full of optimism and determination, thrilled to have my $9,000/year “dream job.” Little did I know I had started on a long and ever-fascinating journey. It is fun to reflect on the beginnings of my career, which nearly coincides with the beginnings of early-initiated diet treatment of PKU.
My interest in PKU actually predated my job in a PKU clinic by several years. It all began with a term paper for an advanced therapeutic nutrition class at the University of California-Davis during my senior year. After a brief exposure to the subject in a previous lecture, I chose PKU for the topic of my research paper. It is remarkable that I still have a vivid memory of sitting at a little desk in the medical library, pouring over the book that first piqued my interest in PKU.
It was a small green book, apparently designed to be the color of a positive PKU screening test (using the old urine ferric chloride test). It was edited by Dr. Frank L. Lyman and simply called “Phenylketonuria.” It held a collection of papers from the leading researchers and clinicians of the early 1960’s (many of whom I later met, or certainly knew of). The book described what was known at the time of the incidence and inheritance, the devastating clinical picture of untreated PKU, the biochemistry, theories on why the disease caused mental retardation, and management of PKU by a special diet. I diligently looked up many of the references from the little green book—over 600 papers were cited, showing the extent of scientific interest in PKU even then—and became fascinated.
I got an “A+” on the paper, as I recall. But more importantly, I had decided on my “fantasy job.” It seemed utterly amazing to me that nutrition could have such a miraculous role in preventing mental retardation (at the time, the first reports of the benefits of early treatment were starting to come out). I thought: this is what I want to do! It was a revelation that came to me so clearly in a certain moment in time, that to this day I still remember the color of that little book.
In fact, when I thought of doing this piece, the color of the book and the author’s name (which I haven’t heard since) came to me instantly! Recently seeing and rereading much of that little book (now bound in bright orange rather than green) brought with it a huge flood of personal memories—and reminded me of where both of us, PKU and I, have come from in these 25 years.
PKU in Its Infancy
I started my job in the Wisconsin PKU clinic in 1972, after a dietetic internship and graduate studies at the University of Wisconsin. I felt so fortunate to have this job—and in a clinic started by one of the well-known “pioneers” in PKU, Dr. Harry Waisman. (He also happened to be an author of a paper in the little green book; unfortunately, he had died the year before I started my job.)
PKU treatment was still in its infancy then. The disease had been discovered back in 1934. But it was not until 1954, when Dr. Hörst Bickel in Germany first constructed a PKU formula product, that it became possible to radically change the natural outcome of PKU. In the early 1960’s, it had been shown in enough cases that the earlier the treatment started, the better the outcome. Shortly thereafter, in 1963, Dr. Robert Guthrie developed his newborn screening test for PKU. It was a sensitive, specific, inexpensive and rapid method for determining blood phenylalanine in a large number of samples at a time. With Dr. Guthrie’s innovative test, and his tireless energy in pursuing his dream of universal newborn screening, we were on our way to early treatment of PKU and prevention of mental retardation.
The Early Diet
Most screening programs in the US started in the mid-1960’s. So in 1972 when I started my job, most of the early-treated children in clinics all over the country were under the age of seven years. We followed only about eight children diagnosed by newborn screening (a small clinic by today’s standards, but large for those times). The only formula available for treatment was Lofenalac, not the many we have now. The only food lists were local collections of several hundred foods, not the thousands we have in the Low Protein Food List for PKU. There were few special low protein foods available and many fewer grocery store foods that could be used. There were not many recipes developed, and almost none that used only natural foods. In fact, most of the published recipes incorporated Lofenalac formula, an abhorrent idea to me and to many families. At least the diet then was a great improvement over the earliest versions, when much less palatable formulas were used.
The first edition of Low Protein Cookery for PKU, published in 1977, was my attempt to expand the possibilities of the diet. Early in my career, I began organizing “mom’s meetings.” I wanted to learn as much as I could about practical management from the real experts, and thought the parents would feel supported. So a group of Wisconsin mothers of young children and I started developing recipes and sharing new food ideas at our frequent meetings. When we started out, we had no plans for this informal sharing to become a published book. But as time went on, we realized that other families could benefit from our efforts. Fortunately, we found a willing publisher, The University of Wisconsin Press. They are an academic book publisher; this was their first (and only) venture into cookbook publishing. I am ever grateful for their enthusiastic support of our small cookbook that went on to expand food possibilities for so many people. It is remarkable that they are now publishing the third edition of Low Protein Cookery for PKU, exactly 20 years after the first (much different) edition was published.
Stopping Treatment: The Divisive Issue
Indeed, the diet was not easy to maintain with the “tools” we had available to us back then. In fact, many clinicians believed that managing the diet beyond early childhood would be a great hardship. The common thinking of the day was that the brain was fully developed by the age of six. It followed, in the minds of many, that stopping the diet around this age likely would not be harmful.
Interestingly, as I recently reread the little green book published in 1962, several researchers even back than suggested the diet should be continued “well beyond early childhood, up to age eight or ten or longer.” But in 1972, diet discontinuation in early school age was the most common practice among US clinicians—and worldwide. There were a few clinicians who vehemently disagreed with this practice. They believed it was not safe for the developing brain and that it was foolish to risk harming a young child by stopping the diet.
I will never forget the passionate arguments on both sides of the issue at a meeting of the National Collaborative Study of Children Treated for PKU in the early 1970’s. I was a “project nutritionist” (one of eighteen) because of our Madison clinic’s involvement in the study. It stunned me to hear clinic directors arguing that “the difficulty of diet management” was even a consideration for justifying why the diet might be stopped. I remember waiting to hear the scientific evidence that would sway me—the evidence that would show the human brain is invulnerable to insult by phenylalanine even after most of its physical growth is complete. There was none.
In my heart, I never believed it was safe to stop the diet. And yet, in our clinic, we continued to allow our children to go off the diet at age six. To try to settle the debate over whether it was safe to stop the diet in early childhood, the national study had decided to randomize its participants to go off the diet or stay on at age six.
In a national survey I did in 1978, 36% of six year-olds and 16% of five year-olds were off the diet. Only a handful of clinics advocated “diet for life.” Whether or not to stop the diet really was the issue of the day—and continued to be for many years.
By around 1978, a number of children in our clinic who stopped the diet had already developed problems: eczema, hyperactivity, mood changes, noticeable drops in I.Q. We finally adopted a policy of continuing the diet indefinitely in 1978 or 1979. At that time, there was also increasing evidence in the scientific literature suggesting it was unsafe to stop the diet at a young age.
Yet controversy still raged. As the years went on, more and more clinics believed the reports, or had negative experiences of their own, and stopped recommending diet discontinuation. Finally, in 1997, I hope everyone is convinced “diet for life” is the only truly safe course for people with PKU. As you can guess from my history, I have been waiting more that twenty years to write the Winter 1997 issue! The time and the forum were finally right. The personal stories combined with the published papers made a powerful statement that I hope will allow even the present-day skeptics to put their doubts behind about the value of the diet. I only hope we can find all of the young people whose diets were stopped due to our prior lack of knowledge and understanding.
Outcome of Early Treatment
In 1972, we were just a short decade away from calling phenylketonuria “imbecilitis phenylpyruvica” or “phenylpyruvic amentia” or “phenylpyruvic oligophrenia.” All of these terms referred to the phenylpyruvic acid found in large quantities in the urine of affected persons—and to the severe brain damage that was known to occur in untreated PKU. It was known that over 90% of persons with untreated PKU had an I.Q. (Intelligence Quotient) less than 60. They were typically classified as “idiots” and “imbeciles” or “low grade or medium-grade defectives.”
I had my first, unforgettable exposure to untreated individuals with PKU early in my career. Our clinic staff decided to visit state institutions for the retarded to draw blood on some residents who had been late-diagnosed and perhaps briefly treated in childhood. We wanted to evaluate the effects of age on off-diet blood phenylalanine levels. The more dramatic thing that we came away with were impressions of the chilling effects of high phe levels in these severely retarded persons. Mental retardation was not their most striking feature; it was the aggressive, often violent and agitated behavior that I witnessed, the terribly unhappy people tormented by the continued toxic effects of phenylalanine on the central nervous system. Those scenes haunt me to this day. I can still hear the tortured cries of one adult male, piercing the quiet of the institution, and another with both hands wrapped in huge wads of gauze to prevent her from biting her own hands until they bled.
The student reading the little green book in 1968 was impressed by the miracle of diet intervention. Twenty-five years later, I am still impressed by what the diet can do. Even though I have not been in the clinic for nearly 10 years (since starting National PKU News), I never stop feeling as proud as a parent when one of the babies I treated early-on in Wisconsin graduates from college or gets a fabulous job or does something wonderful—all while still on the diet that once was thought to be “impossible” to maintain beyond childhood. With good treatment and “diet for life,” we now know that anything is possible. Children diagnosed early with PKU have every hope of reaching their full genetic and human potential.
These are just a few of my more vivid personal recollections of the early days of PKU treatment and my involvement. Of course, there are many other issues and problems that have come up over the years. For some, we have answers. We can guess that the next twenty-five years will bring many more answers to our questions and solutions to our stumbling blocks—and ultimately an easier treatment or a cure for PKU. I hope that I am around to hear about these things, if not to be part of the process.
People often thank me for being there all of these years—but now it is my turn to thank all of you for the opportunity to do what I do. I want to thank everyone who has been a part of my “PKU world” over the years. I can’t imagine life without you! I can’t imagine not having the love and support and friendships and good wishes that come because of my work in this extraordinary career that I stumbled upon twenty-five years ago. And thanks to “the little green book” that started it all. It has been a remarkably rich and rewarding time—and I hope (and expect) the same in the years to come.