ORGINIALLY PUBLSIHED AT : http://pkunews.org/personal/parent.htm

PKU: A Parent’s Case Report

By Kurtis Sauder, M.D.

Dr. Sauder, a pediatrician in a group practice through the University of Virginia, is the proud father of two young children with PKU.

General Information about PKU

“Phenylketonuria” (PKU) refers to a group of autosomal recessive inherited abnormalities of metabolism of the amino acid phenylalanine. The inability to convert phenylalanine to tyrosine results in high levels of phenylalanine which are neurotoxic. Classical PKU is a deficiency of the enzyme phenylalanine hydroxylase (PAH) which is required for the conversion of phenylalanine to tyrosine. Varying degrees of PAH deficiency as well as disorders of tetrahydrobiopterin production or regeneration leading to hyperphenylalaninemia make PKU a heterogeneous disorder. Tetrahydrobiopterin is a cofactor necessary for the normal function of phenylalanine hydroxylase.¹

PKU was discovered in 1934 by Dr. Asbjorn Folling, who detected phenylpyruvic acid in the urine of two mentally retarded siblings.² If left untreated, PKU leads to progressive developmental delay, severe mental retardation (95% with IQ less than 50), seizures, autistic-like behaviors, a peculiar odor, hyperactivity and eczema.¹

Fortunately, universal newborn screening, first made possible by the Guthrie test³, in the United States allows early detection of hyperphenylalaninemia and early initiation of a diet low in phenylalanine. This is accomplished by starting a reduced phenylalanine diet, including a phenylalanine-free formula, and avoiding foods high in protein. Phenylalanine levels are monitored on a regular basis and intake of phenylalanine is adjusted accordingly to keep levels in the acceptable range (2-6 mg/dl). Since phenylalanine is an essential amino acid, a diet completely devoid of phenylalanine would not support normal growth and development. The formula provides other amino acids, which are not available in sufficient amounts in the low-protein diet. When adequate dietary control is maintained, children with PKU can be expected to have grossly normal growth and development.⁴ However, subtle neuropsychological impairments have been reported in persons with treated PKU.^5-8 In addition, relaxation of dietary control later in childhood, previously the standard of care, has been reported to lead to neurologic, cognitive and psychological deficits in some patients, as well as partially reversible white matter changes on MRI.^9-15

Our Story

June 24, 1996 was the proudest day of my life. It was the day of my son Zachary’s long-awaited and much-anticipated arrival, albeit a month earlier than we expected. Everything went smoothly and after a brief re-admission for dehydration from poor feeding related to his prematurity, we were back at home enjoying being parents. When Zach was a week old, we received a call from his pediatrician, who is also a friend and mentor, informing us that his newborn screen revealed an elevated phenylalanine level. My immediate reaction was one of panic because I realized that I did not have any idea what it really meant to have PKU. All I remembered was some peripheral reference to it during medical school biochemistry. I was also a little embarrassed because, since I was chief resident in pediatrics at the University of Virginia at the time, I figured that I should probably know all about this. The result had already been discussed with our metabolic specialist and the hope was that this represented transient neonatal tyrosinemia, a benign condition more common in premature infants. I went home to discuss it with my wife and we arranged to have his plasma amino acids checked the next day.

We spent most of that evening sitting on the couch, holding Zach, and staring into space. I looked up PKU in Nelson’s Textbook of Pediatrics at home. In the book it sounded easy -– start a phenlyalanine-restricted diet and avoid the mental retardation and seizures. In retrospect, I had no idea of the practical ramifications of a low-phenylalanine diet. Unfortunately, Cindy had done a report on PKU in high school, and all she could remember was that it causes mental retardation. I really do not remember too much about that evening but I suspect that we did not sleep too much.

The next morning, we took Zach to our pediatrician. Prior arrangements had been made to provide us with a quick answer. We had decided the night before to assume that he did have PKU – that way we would not be disappointed if he did and we would be pleasantly surprised if he did not. I went to work to keep my mind on other things which, in retrospect, was a bad idea because it left Cindy at home alone with Zachary with nothing to do but worry. Sometime that afternoon we were told that he did have PKU. I do not remember exactly how we found out. All I remember is walking in the front door at home to find Cindy holding Zach and crying. I badly wanted to reassure her but I was also scared because I did not really know what this would mean for us. How do you do this weird diet? Would he be normal? Could he still play sports in high school? I also realized that my genome is not perfect. I was partially responsible for my son’s disorder.

The metabolic specialist, another mentor of mine, came to our house that evening to explain things to us. As he did the calculations to see how much phenylalanine-free formula and how much standard cow’s milk formula Zach should eat, I realized that this was going to be more of a challenge than just avoiding hamburgers.

We have subsequently learned a lot about the “weird” diet. Zachary is not able to eat foods such as meat or eggs, which are high in protein. Dairy products, legumes and flour, which are also relatively high in protein, can be eaten only in very small amounts. He eats a lot of fruits and vegetables as well as specially ordered low-protein foods such as bread and pasta. We perform finger sticks at home monthly (initially we did this twice a week and gradually decreased the frequency to once a month) and collect the blood on filter paper to be sent to the state lab to check his phenylalanine level. His level at the time of diagnosis was 22 mg/dl and our treatment goal is 2-6 mg/dl. Because he does not eat much protein, he drinks a phenylalanine-free formula to provide him with amino acids. This is all done with the help of a nutritionist who specializes in children with metabolic disorders.

We carefully calculate his daily intake of phenylalanine so as not to exceed his limit. This is accomplished by weighing the food he eats and then calculating, with the help of the Low Protein Food List for PKU, his intake of phenylalanine, which is about 400 mg per day. Avoiding high protein foods seemed fairly straightforward until we actually realized how much phenylalanine is in foods that I had never thought of as sources of protein (Table 1). In addition to the food list, we have several PKU cookbooks, which tell how much phenylalanine is contained in the recipe. There are a variety of low-protein food products available – from flour and pasta to Easter eggs – which can be used to make low-protein dishes.

Table 1

Understandably, the phenylalanine-free formula and low-protein food products are quite expensive (Table 2). Some states have legislation requiring insurers to pay for the formula and food products. In Virginia, there is no such legislation but the formula is provided on a sliding scale, based on income, through the Department of Health. Our health insurance covers the formula but not the other food products. The monthly monitoring blood phenylalanine levels are provided free of charge by the state.

In the last three years, we have experienced a variety of feelings and frustrations. Initially, we had difficulty doing heel sticks at home to check his level. Why can I perform endotracheal intubation or put arterial lines in someone else’s baby but I can’t even get enough blood from a heel stick on my son? We also had an initial scare when his urinary pterin screen, looking for PAH cofactor deficiencies was abnormal. Cofactor deficiencies are not as amenable to dietary management because tetrahydrobiopterin is necessary for other biochemical pathways in the body other than the metabolism of phenylalanine. When I told my wife about his abnormal pterin screen and told her that only 1% of children with hyperphenylalaninemia actually have a cofactor deficiency, her reply was, “Yes, but the incidence of PKU is one in fifteen thousand and he has that.” It was difficult to disagree with that logic but his follow-up test was normal.

Table 2

Zach now notices when he is eating something different than we are. He understands that he eats “special” food and enjoys being quizzed about what are and are not “Zach foods.” Should we always eat PKU-friendly foods at home? Should we eat different foods so that he learns he can’t just eat anything? We end up doing some of both. I must confess that I frequently get my protein fix away from home by stopping for a hamburger on the way from the office to the hospital or other times when Zach is not around.

Restaurants, vacations with friends and church picnics are a challenge. We once took him to a restaurant with an eight-page menu and there was nothing there that he could eat. Fortunately, most places have French fries, which are fairly “high” but can be eaten if he has had “low” things at the other meals that day, or a salad bar from which we can get him tomatoes, cucumbers or other vegetables to eat. I always feel a little silly pulling out his scale in the middle of a restaurant to weigh his French fries so sometimes we just estimate although my wife is much better at estimating than I am. I have never noticed a reaction from other patrons when we pull out the scale but we frequently need to give at least a brief explanation to our server to convince her we do not need to look at a children’s menu.

Baby sitters, the church nursery, visiting with family members, etc. also provide extra challenges. Fortunately our friends and family have taken an interest and are careful not to give him things they are not sure about without asking. His grandmothers have PKU cookbooks and like to make him things. However, when Cindy was ill recently, the combination of Daddy, family and friends was not nearly as adept at managing the diet as the real expert – Mommy.

We wonder about the future. How and when do we explain this to him when he is older? For now, he knows that he eats special food because it is good for his brain. What about eating hot dogs at baseball games and frying our freshly caught fish over a fire? A lot of father-son bonding moments, which I had envisioned before his birth, involve ingesting protein. What if he eats something at school that he should not have? Will he rebel as a teenager by eating Big Macs? Will he have learning difficulties, hyperactivity, or psychological problems, all of which are reported to be more prevalent in treated PKU?

Others have many questions for us. “Will he grow out of it?” Not really. The effects of hyperphenylalaninemia decrease with age but he will never have the enzyme. “How long does he need to stay on the diet?” Probably forever. Children who have come off the diet, even late in childhood, have been reported to have minor neurologic, cognitive and psychological problems. “What about prenatal diagnosis?” This is not routinely available and, even if it was, would not be an issue for us. Even if we viewed abortion as an option, how could we possibly terminate a pregnancy because of PKU when Zachary is the best thing to ever happen to us?

In fact, Zachary’s little sister, Rachel, is now a month old and also has PKU – a mild surprise to us since the chances of her having PKU were only one in four. This time around it is not a big deal. We know how to do the diet. We can look at her big brother and know everything is going to be fine. And Zach is proud to know that “when Rachel gets big, she will eat special food like me.” Underlying our worries, has always been a deep gratitude. Gratitude that Zach and Rachel were born in the era of routine newborn screening and effective dietary management, and that they can be a normal children on a weird diet instead of two of Dr. Folling’s “imbeciles” which he first described in 1934.

So what does this have to do with me being a pediatrician? I think of the mother of the child with ornithine transcarbamylase deficiency, whom I met when I was a resident. As she was describing her child’s diet, I was thinking about the million other things I needed to do and thinking that this was really too bizarre to have any practical educational benefit for me. Now I am explaining my children’s diets to others. I am reminded to listen to the mothers of children with chronic disorders because Cindy knows off the top of her head how much phenylalanine is in a graham cracker. If either of our children were ever in the hospital, the most appropriate diet order would be “per patient’s mother,” because very few physicians would have any clue how to do it. I have less tolerance for parents who tell me, “he won’t eat anything but potato chips,” because I know from experience, a child will eat what is available to him.

I think of the parents of children to whom I have given very bad news – leukemia, severe brain damage, or the death of their child. I wonder how parents, many of whom do not have access to the same supports and resources that I do, deal with children with severe illnesses when a “nuisance” diagnosis caused us so much worry. I understand why we need to repeat things over and over to parents who have just received an unexpected diagnosis. They need the diagnosis to sink in before they are ready to digest details and they need time to formulate all of their questions. I understand why parents need reassurance for seemingly trivial things – if you think your child is at risk for developmental delay, any milestone not reached exactly on time is a potential life-long disability. I realize how it sounds to a parent when someone says, “He has PKU,” instead of “he is a happy, healthy child who happens to eat an unusual diet.” I wonder what it feels like to unwittingly pass along a devastating genetic disease to your child, like Huntington’s disease or spinal muscular atrophy. I am supposed to protect and care for my children, not give them diseases. If nothing else, I have gained a new perspective, which I hope translates into making me a better pediatrician.

As for Zachary and Rachel, they are fine. You would never know they have PKU unless you saw us weighing the French fries or heard us request a happy meal with salad (no cheese, please) instead of a hamburger.

References

1. Rezvani I. Defects in Metabolism of Amino Acids. In: Behrman RE, Kliegman RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 15^th ed. Philadelphia: W.B. Saunders, 1996: 329-333.
2. Folling I, The discovery of phenylketonuria. Acta Paediatr Suppl 1994; 407: 4-10.
3. Guthrie R and Susi A, A Simple Phenylalanine Method for Detecting Phenylketonuria in Large Populations of newborn Infants. Pediatrics, 1963; 32: 318-343.
4. Smith I, Treatment of phenylalanine hydroxylase deficiency. Acta Paediatr Suppl 1994; 407:60-65.
5. Smith I, Beasley MG and Ades AE, Intelligence and quality of dietary treatment in phenylketonuria. Arch Dis Child 1990; 65: 472-478.
6. Waisbren SE, et al, Review of neuropsychological functioning in treated phenylketonuria: an information processing approach. Acta Paediatr Suppl 1994; 407: 98-103.
7. Kalverboer AF, et al, Social behaviour and task orientation in early-treated PKU. Acta Paediatr Suppl 1994; 407: 104-1
8. Peitz, J, et al, Psychiatric Disorders in Adult Patients with Early-treated Phenylketonuria. Pediatrics 1997; 99(3): 345-350.
9. Koch R, et al, Preliminary report on the effects of diet discontinuation in PKU. J Pediatr 1982; 100(4): 870-875.
10. Seashore MR, Loss of Intellectual Function in Children with Phenylketonuria After Relaxation of Dietary Phenylalanine Restriction. Pediatrics 1985; 75(2): 226-232.
11. Ullrich K, et al, White matter abnormalities in phenylketonuria: results of magnetic resonance measurements. Acta Paediatr Suppl 1994; 407: 78-82.
12. Arnold GL, et al, Factors affecting cognitive, motor, behavioral and executive functioning in children with phenylketonuria. Acta Paediatr 1998; 87(5): 565-70.
13. Potocnik U and Widhalm K, Long-Term Follow-Up of Children with Classical Phenylketonuria After Diet Discontinuation: A Review. J Amer Coll Nutr 1994; 13(3): 232-236.
14. Bick U, et al, White matter abnormalities in patients with treated hyperphenylalaninemia: magnetic resonance relaxometry and proton spectroscopy findings. Eur J Ped 1993; 152: 1012-1020.
15. Burgard P, et al, Psychopathology of patients treated early for phenylketonuria; results of the German collaborative study of phenylketonuria. Acta Paediatr Suppl 1994; 407: 108-110.
16. Schuett VE, Low Protein Food List for PKU. 1995.

Last update: 07/00
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