I was late diagnosed, and taken off the diet at 12 years old, 1972. Big mistake if my mom and I would have known the consequences we would have never allowed it. But the damage is done (some permanent) nothing left to do but prevent more. I pretty much live by a quote from Haunted Mansion--"You try, you fail, you try you fail, but the real failure is when you STOP trying" I know article is long but worth the read.
Off-Diet Young Adults with PKU: Lives in Danger
By Virginia Schuett, MS, RD, Editor, National PKU News From the Winter 1997 issue (Vol. 8 No. 3) of National PKU News
On September 27, 1996, Tom Brokaw moderated the American Dream segment of his NBC nightly news cast. Remarkably, it dealt with PKU, a rare national exposure. The segment started something like this: A doctor is still on the job in his 70's. Dr. Richard Koch, at age 74, is still a man on a mission. For fifty years he has worked at Children's Hospital in Los Angeles. He says he cannot retire because he has urgent, unfinished business to take care of. The urgent, unfinished business to which Tom Brokaw referred, is Dr. Koch's mission to find all young adults with PKU who are lost to follow-up. It is his passion, his American Dream, Mr. Brokaw said.
The story went on to give a brief history of PKU. It talked about how the PKU diet used to be stopped at around age six, and how it took years for clinicians to realize the folly of that practice. It mentioned the lower I.Q.'s and other problems that can develop due to high phenylalanine levels. It also pointed out the danger of high levels to the unborn children of pregnant women with PKU. In an interview, Dr. Koch goes on to say, Many PKU adults who have abandoned the diet may not know they are still at risk. It hurts when we cannot find these young people to help them.
A few days earlier, on September 15, 1996, a Los Angeles Times' article focused on Dr. Koch's mission. In it he said, Even male PKU patients, or female PKU patients who are not contemplating pregnancy, should consider restarting the diet. Recent studies show that high phenylalanine levels (above about 14-15 mg/dl (840-900 mol/l) in PKU patients who have the more serious forms of the genetic defect may cause continued neurological damage in adulthood. One of my biggest problems is talking people into going back on the diet.
I share Dr. Koch's concerns for off-diet young adults. I am deeply concerned about anyone who has stopped the diet whether early-treated or late-treated, teens, young adults or older adults. This has been a prime worry of mine for years. But especially in the last year, I have heard from more and more parents and young people whose lives have been needlessly altered by the cruel effects of toxic phe levels. It seemed time that I devote most of a newsletter to this problem and attempt to reach as many people as possible with the message. And so Lives in Danger is the theme of this issue.
Dr. Koch has long been at the heart of PKU treatment and research. This is through his clinical work (for 42 years, following hundreds of patients with PKU). It is also through his leadership of the two large US PKU research studies, the first starting in 1966. He has recently published a revealing paper in a scientific journal that relates to our concern for young people no longer on treatment. Its title is Care of the Adult with Phenylketonuria (Eur. J. Pediatr. 155 [suppl]: S90-S92, 1996). The purpose of the study was to report I.Q., academic achievement and social progress in three groups of adults with PKU. Here is a summary of Dr. Koch's findings.
The Study Group
Group 1 consisted of 18 adults who were identified by newborn screening and one by screening because of a sibling previously identified. The average age at diagnosis was 2.6 weeks. All in Group 1 remained on the diet at the time of the study. These individuals had excellent control for the first six years of life. At the time of the study, nine subjects in Group 1 were in good control, with blood phe levels less than 15 mg/dl (900 mol/l). Nine others had fair control, with blood phe levels consistently below 20 mg/dl (1200 mol/l). One had poor control, with levels above 20 mg/dl. Those in this group had frequent levels of 10-18 mg/dl (600-1080 mol/l) during their adult years, but all continued to consume the medical product. The average age was 22 years (range 18-27 years).
Group 2 consisted of 21 adults identified by newborn screening and three by screening because of a sibling previously identified. All in Group 2 stopped the diet at an average of 7.8 years (range 5-10 years), and have been off-diet for an average of 18 years. Seven in this group had good control before stopping the diet, 11 had fair control and 6 had poor control. Their average age was 26 years (range 18-33 years).
Group 3 consists of 19 adults who were identified before newborn screening programs existed, based on symptoms due to high phenylalanine levels. The average age at diagnosis was 2.7 years. All in this group continued the diet into adulthood. Nine in Group 3 had been off the diet for varying periods, but resumed the diet when it was recommended. Eleven in the group had good control, two had fair control and five had poor control. Their average age was 27 years (range of 18-36 years).
Study Results
The individuals in Group 1, those early-treated and still on the diet, had an average I.Q. Of 104 (range 74-123). Of this group, 78% attended college, two are married and one has a child. Eleven have steady jobs and seven are still in college; only one is unemployed. None are on Social Security, general relief, or have been arrested.
In Group 2, those individuals who were early-treated but stopped treatment at a young age, the average I.Q. was 92 (range 69-116). This is an average of 12 points lower than those who continued the diet. Their phe levels off the diet ranged from 15-40 mg/dl (900-24 mol/L). Only seven (28%) of this group attended college, and just four graduated. Fifteen are currently employed, but five are on welfare and one is mentally ill. Six are married, but five live in common-law relationships. They have had a total of nine children; all are unplanned pregnancies among the thirteen women in this group. (Three pregnancies were aborted electively; two resulted in offspring with serious congenital heart disease.) One individual who has been off the diet for 25 years is unstable, chronically unemployed and impotent despite blood phe levels of only 10-20 mg/dl (600-1200 mol/L).
In Group 3, those individuals who were diagnosed late, the mean I.Q. was 83 (range 55-108). This reflects a gain of 20 I.Q. points since age six and an even greater increase since treatment started. Four in this group are homemakers; only one is married. They have given birth to ten children. Five in Group 3 are on welfare and one has been arrested for pedophilia.
What The Study Tells Us
These data confirm earlier reports that suggest stopping the diet is harmful not only to intellectual development, but also to social functioning. The intellectual and academic achievement of Group 2 is significantly inferior to Group 1; also, their social adaptation is poor. Unemployment, out-of wedlock pregnancies, and welfare assistance is greater in this group.
Neurological complications, which have been described in adults off treatment, were not observed in these adults. But those off the diet may be at risk in the next decade or two. Dr. Koch notes he has observed significant neurological deterioration in two untreated subjects not included in this report, after 26 and 33 years off the diet. Long-term studies are needed to evaluate the future course for individuals in this report.
Interestingly, in Group 3, nine individuals currently have an I.Q. in the borderline range of mental retardation despite very late treatment. The nine whose I.Q's were in the normal range had scores of 86 to 108. The adult with the I.Q. of 108 (above average) is the only one with an I.Q. over 100. She was diagnosed with PKU at 1 1/2 years and had a developmental quotient of 60 (mentally retarded range). By age six, her I.Q. was 101. She is one of the only two to go to college in this group. Another subject in this group was found to have PKU at age 2 1/2 years and had an unmeasurable I.Q. Now at age 21 and under good diet control, she is helpful around the house, has all of her self-help skills, plays the piano well and can communicate.
The data reported in this study strongly support the conclusion that dietary phenylalanine restriction should be continued into adulthood. The data also show that late-treated adults with PKU can do surprisingly well when continued on diet treatment.
Other Scientific Evidence Adds To Our Fears
There is an abundance of other evidence to augment our concerns for off-diet young people. Here are a few of the more striking and perhaps less known findings.
Mental Illness & Psychological Disorders
There appears to be a definite increase in the incidence of mental illness and psychological disorders in the off-diet PKU population. For example, a recent paper by Fisch (1995) studied nineteen early-treated adults with PKU who had been off the diet for at least 12 years (range of 12-28 years off diet). Five (26%) of the group had evidence of mental disease. This included two with depression, one with impulse control disorder, one with a phobia, and one with mental distress.
A study by Waisbren (1991) describes agoraphobia (fear of leaving the house) in five adult patients who had stopped the diet in childhood. Those who restarted the diet had a dramatic reduction in symptoms. Other off-diet adults who were studied showed a tendency to social withdrawal and fear of leaving home, but not overt agoraphobia. Waisbren (1994) describes a greater prevalence of thought disorders and mood disturbances associated with stopping the diet in their study of twenty-eight young women. They concluded that if a woman with PKU is late-treated or off-diet for at least five years, she will be at risk for developing some type of emotional disorder. She will also be more likely to receive psychological counseling and to be on medications for psychological problems. (Males with PKU were not studied.)
Neurological Deterioration
There are also neurological changes that appear to be related to high phenylalanine levels. A dramatic report by Thompson (1990) discusses seven young PKU adults who developed neurological disabilities in adolescence or early adult life, many years after stopping diet (or in two, after a period of very poor control). All had signs of motor neuron damage. The presenting features were epilepsy resistant to anticonvulsant therapy(1), severe tremors (1), and spastic paraparesis or quadriparesis (5).* One of the latter became wheelchair-bound at the age of 21 years. Three subjects restarted the diet; two showed clear improvement (the wheel-chair -bound woman was able to walk long distances after 2 years) and one showed possible improvement.
The authors suggest these cases may be an extreme manifestation of a much more common defect. An earlier study (Clarke 1987) lends credence to this idea. Nine adolescents on a free diet for 2 to 11 years showed prolonged reaction times on testing. A highly significant improvement occurred when the diet was restarted.
Another report (Villasana1989) describes a 28 year-old late-treated male who stopped diet at age 12. He developed rapidly progressive spasticity that left him wheel-chair-bound, and had increased seizure activity. Two months after restarting diet, he could walk more than a mile unassisted. Ishimaru (1993) also reports on a male in his forties who developed multisystem neurological problems; his gait deteriorated until he was wheel-chair bound. McCombe (1992) reported on a 19 year-old male who developed spastic paraparesis just 8 months after stopping diet. The spasticity gradually improved after he resumed diet.
There are scores of reports on abnormal Magnetic Resonance Imaging (MRI) studies of the brain in PKU that have been reported in the past few years. Thompson (1993) shows that in early diagnosed subjects, the severity of MRI changes were significantly related to how high the phenylalanine levels were and the time since dietary control had stopped. It is believed that the abnormalities represent changes in brain myelin (myelin is the sheath that covers brain nerve fibers). While the abnormalities have been shown to be at least partially reversible, the authors suggest that high phe levels pose a lifelong hazard to the central nervous system. Bick (1993) concluded from their study that a normal MRI is only found in patients with blood phenylalanine levels continuously below 6 mg/dl (360 mol/L)
A report by Battistini et.al. (1991) described a young woman who stopped diet at age 5. At age 18, she developed anxious-depressive symptoms, deterioration of school performance and MRI abnormalities. Returning to the diet diminished not only the psychiatric problems, but the neurophysiological and MRI changes as well. A report by Cleary et.al. (1995) describes patients with abnormal MRI's. MRI was repeated in five patients who returned to a strict diet after 3-12 months. Scans improved in all five.
Are there more such cases not reported in the scientific literature? Almost certainly. Case studies are not commonly written or published these days. And doctors treating adults may not associate their problems with PKU, or even know about the PKU.
The simple conclusion we can come to from all of these reports is that high blood phenylalanine levels are not safe for anyone; they never have been, they never will be. We know that high levels of phenylalanine alter metabolic balance in very far reaching ways, from disturbing neurotransmitters to interfering with brain myelin.
In Your Editor's View
I have many stories of my own, from parents and young adults who have called me, written me or e-mailed me for help. Several of those are featured in the special colored insert. Others include the early-treated woman who became schizophrenic as a young off-diet adult (the diet has helped her condition greatly, but she is still not normal); the young man who was arrested for arson as a troubled teen off the diet (isn't it reasonable to think that judgment can be affected?); the young man who developed terrible bleeding eczema (completely cured with diet); the young woman who developed migraine headaches and became lethargic and depressed (reversed by diet).
Other symptoms described to me include mood alterations, lack of ability to concentrate, loss of short term memory, poor academic functioning or inability to hold a job, muscle weakness, tremor and poor personal relationships. While not every problem can be directly linked to high phe levels, given what we know about phenylalanine and the human body, there is a strong likelihood the problems are related.
Fortunately, I think all clinics in the US and elsewhere finally now agree that treatment needs to be continued. Families new to PKU should be hearing this message loudly and clearly. But what about those families of young adults who went off the diet as young children or teens, when we weren't as wise as we are today?
The sad truth is that there is no way to predict who will be most affected by high levels of phenylalanine. I believe that no one is immune to its effects, but that some individuals are more vulnerable than others. This may relate to the specific genetic mutation involved. Unfortunately, we do not know yet which mutations, or which combinations of mutations, lead to the greatest vulnerability. And even though some individuals appear not to have problems with high phe levels in the short-run of a few years, who knows what will happen to them in the long-run? What will happen to everyone with an elevated phenylalanine levels after exposure for 20 or 30 or 40 or 50 years? Will all of our early-treated young people with PKU who are off the diet or poorly controlled eventually have some kind of mental or neurological disability, or will their lives be compromised in some way? To me, it is irrational for anyone to gamble with those possibilities. Life is challenging enough without the burden of a neurological or psychological handicap.
I believe all off-diet young adults should return to the diet for their long-term welfare. It is not enough for us to be concerned about young women and the maternal PKU issue. We have to be concerned on a national level about both young women and young men. We cannot assume MRI abnormalities mean little. We cannot assume all of the problems that will develop due to high phe levels are reversible. We cannot blithely assume only a few people will be affected in the long-run.
Reaching Off-Diet Persons
In the past few years, I have been contacted by numerous families of off-diet young people who did not know the current thinking about diet. Their sons and daughters had stopped the diet years ago and were having problems of various sorts. They found out about National PKU News only by chance connections with friends, our World Wide Web site, etc. They had not been seen by a clinic for many years, nor had the clinic contacted them for follow-up. When I told them about the present thinking, they were appalled they had not been informed. Who can blame them? It is a tragedy.
There must be at least several thousand young adults who are off treatment. In a 1987 national survey I did, there were nearly 1500 identified. This number did not include those lost to follow-up. It is my American Dream that every single person who is no longer on treatment will have a chance to consider the long-term risks and the option of restarting it. I have heard of so many young adults who have done this successfully (for example, see Chris Pierson's story on p. 11). They are grateful for the positive changes they have experienced and the peace of mind they have in doing the best they can for their health and welfare.
Don't we in the medical profession owe all persons with PKU the knowledge that will enable them to make informed decisions about their lives? Isn't it a moral obligation? The fact is, most patients who are lost to follow-up can be found, albeit with some effort. I hope that all clinics will attempt to locate these individuals, if they have not already. I would also be glad for ideas from anyone about how to reach this lost group. I had hoped to write an article on this issue for a national women's magazine, but was turned down by six different magazines.
Yes, there will be roadblocks for those who decide to restart the diet. I do not minimize the potential difficulties. Paying for the medical food and low protein foods is one difficulty. And counseling and advice from often overburdened clinic staff will be necessary. In spite of the obstacles, we should not rest until every person with PKU is fully informed about the dangers of high phenylalanine levels.
This article and many other helpful information can be seen at www.pkunews.org. Virginia Schuett keeps pkunews up and running with lots of good info, stories video, links, and legislation 
