by
Barbara E. Dolan, RN, MSN
Nurse Counselor for Genetics, Redwood Coast Regional Center, Ukiah, CARichard Koch, MD
Division of Medical Genetics, Children’s Hospital of Los Angeles and The Department of Pediatrics, University of Southern California, School of Medicine, Los Angeles, CA

Christina Bekins, MS, RD
Nutrition Consultant, Calistoga, CA

Virginia Schuett, MS, RD

Nutritionist and Director, National PKU News, Seattle, WA

Acknowledgments

The authors applaud the “outreach clinic model” staffed by specialists including Richard Goldwasser, MD, psychiatrist. We wish to thank Kathleen Schmidt Yule, RN, MS, UCS, NBS Program; Kathleen Dall, RD, Scientific Hospital Supplies, Inc.; The Inherited Metabolic Disease Clinic, Denver, CO; and Steven Yannicelli, MMSc, RD and Phyllis Acosta, PhD, RD, Ross Laboratories for their interest and guidance in the beginning months of this project. We are grateful for the interest, confidence and love of adult care providers and their families, and for their willingness to collaborate and share with us.

Note: Before applying any of the information contained in these guidelines to treatment of PKU, you must consult with a PKU specialist. The guidelines do not give advice or recommendations for individuals, whose unique medical, nutritional, and other needs must be considered.

Contents


Introduction

  • Purpose and Approach of the Guidelines
  • A Brief Introduction to PKU
  • Behavioral and Psychological Problems of Untreated Adults
  • Justification for Starting a Low PHE Diet in Adults
  • Special Considerations for Starting the Low PHE Diet
  • Our Positive Experience with Two Adults
  • Overcoming Obstacles to Treatment: Obtaining Information, Guidance, and SupportStarting and Maintaining the Low PHE Diet for Adults
    • The Treatment Support Team
    • Helpful Strategies to Reach Treatment Goals
    • Basic Diet Principles
    • Goals for Lowering Blood PHE Level
    • Starting and Maintaining the Diet
      • Biochemical Testing
      • Guidelines for Introducing the Diet
      • Other Hints for Managing the Diet
      • Diet Precautions
      • Managing Illness
      • Persistence is the Key

    Other Treatment Considerations

    • Antipsychotic or Major Tranquilizer Medications
    • Behavioral Support and Controlling Anxiety
    • Changing Attitudes about Food
    • Costs and Benefits of Treatment
    • Considerations of Aging

    References

    Diet Resources

    • Recipes and Diet Information
    • PKU Medical Formula Products
    • Low Protein Specialty Products

    Appendix

    • Case Histories: Two Adults with PKU
    • Sample Menus (will be available at a later date on the PKU News web site)

    Introduction

    Purpose and Approach of the Guidelines

    The purpose of these guidelines is to present an organized way to start and maintain a phenylalanine (PHE)-restricted diet for a previously untreated adult with phenylketonuria (PKU). The guidelines draw on the first three authors’ successful experience with diet initiation and maintenance in two mentally retarded adults with PKU living in a residential setting. The guidelines are to be viewed as a starting point, which can be expanded and modified as other people gain experience with diet management for previously untreated adults. The guidelines also can be adapted for use with adults living in a home situation

    Our approach to treatment encompasses the following:

    1. gradually introducing the PKU medical formula product while decreasing natural dietary protein;
  • slowly introducing unfamiliar lower protein foods;
  • individualizing quantities of the PKU medical formula product in response to regular biochemical monitoring;
  • reassessing the adult’s current antipsychotic drug use.A Brief Introduction to PKUPKU is an autosomal recessive genetic disorder in which an individual inherits a specific gene mutation from both healthy parents who are “carriers.” A “double dose” of the mutated gene in the baby results in deficiency of a liver enzyme, phenylalanine hydroxylase. This enzyme normally converts the amino acid, phenylalanine (PHE), into another amino acid, tyrosine (TYR). Because the enzyme is either missing or defective in its activity, serum PHE levels become elevated and harm the developing central nervous system of affected persons. If PKU is not diagnosed in the early weeks of life, the chronically high PHE level causes mental retardation and a variety of other problems.Babies born with PKU in the US and many other parts of the world today are identified in infancy through newborn screening programs. They are immediately started on a PHE-restricted diet. Early diagnosis and treatment prevents mental retardation and other associated problems. Many early-treated young adults with PKU are now in college, or have completed college and have productive jobs.For years after the start of newborn screening (in the 1960’s), there was controversy over the length of time diet treatment was necessary. Today, however, there is an abundance of data showing that low blood PHE levels are crucial for healthy brain and neuropsychological functioning. There is almost universal consensus among clinicians that “diet for life” is the best approach for the early-treated population.We believe that previously untreated adults with PKU also can benefit from the diet. In fact, we believe the diet should be considered whenever it is feasible. In adults who are untreated, the major goals are positive health, and emotional and behavioral stability.Before the 1960’s, PKU was not routinely diagnosed in the newborn period. Most persons with PKU born before 1965 were never offered treatment, or were diagnosed late and treated for varying short periods in early life. As a result, most adults born in the era before newborn screening are mentally retarded and may have many problems associated with chronic high blood PHE levels.

    Problems of untreated adults with PKU include (but are not limited to) those listed below:

    Behavioral and Psychological Problems

    • hyperactivity
    • irritability
    • inability to sit
    • sleep disturbances
    • pacing
    • psychomotor agitation
    • temper tantrums
    • uncontrollable attacks of rage
    • short attention span
    • erratic or aggressive behavior
    • poor ability to follow directions
    • poor ability to learn new things
    • psychotic behavior
    • destructiveness
    • self-injury and self-mutilation
    • autistic-like behavior

    Neurological Problems

    • mental retardation
    • seizures
    • tremors
    • muscular hypertonicity or hypotonicity
    • whole body repetitive movements
    • spastic paraplegia, quadriplegia or tetraplegia

    Other Problems

    • eczema (can involve large areas of the body)
    • sensitivity to sunlight and very light skin (due to excess PHE inhibiting melanin formation)
    • body odor identified as “musty” or “pungent”

    Justification for Starting a Low PHE Diet in Adults with PKU

    There are numerous reports in the scientific literature that support the value of starting a low PHE diet for previously untreated adults with PKU (or for late-treated adults who may have been on the diet for only a short time). Many anecdotal reports shared with the authors also substantiate the benefits of the PKU diet for this group of adults.

    Positive changes in adults have included (but are not limited to):

    • decreased aggressive behavior and other disruptive behavior
    • decreased irritability and hyperactivity
    • increased ease in bathing and dressing
    • decreased neurological symptoms
    • increased verbal communication and appropriate eye contact
    • decreased episodes of incontinence
    • improved intellectual functioning (particularly attentiveness and productivity)
    • improved mood
    • increased social awareness
    • disappearance of eczema
    • decreased body odor

    Not every individual with PKU will have the same problems, nor the same response to the diet.

    Yannicelli and Ryan (1995) conducted a survey of 256 residential facilities. In the 57 survey responses, information was provided on 88 adults with PKU. More than one-half of the group was identified as starting on the diet after 35 years of age. In 46% of these adults with late treatment, positive changes occurred after diet intervention and a reduction in serum PHE level. These positive changes included those listed in the paragraph above. (For those adults who showed no significant improvement, no information is available about the duration of treatment or quality of blood phe control.) In those adults who showed behavioral improvement, 40% were able to reduce or eliminate antipsychotic drug use.

    Care providers in the national survey reported positive behavioral changes in adults within three weeks to two months after the blood PHE level dropped within the goal range. In conjunction with diet, 80% of the institutions also used behavior modification programs.

    The survey results brought out the importance of adequate TYR levels (discussed later). There is evidence to suggest behavior improvement may be dependent on the availability of TYR for synthesis of catecholamines. Few adults were provided a TYR supplement with the diet in the survey, and their TYR levels are unknown. It is thus possible that low TYR levels contributed to lack of behavioral improvements in some adults. (However, TYR supplements are not necessarily required to keep serum TYR in the normal range of 0.9-1.8 mg/dl).

    Special Considerations for Starting the Low PHE Diet in Adults

    These guidelines have been developed to help start the PKU diet for any formerly untreated adult who would benefit from an increased quality of life.

    Consider instituting the diet in the following instances:

    1. Where multiple medications have been unsuccessful in controlling agitation and/or screaming;
    2. Where the long-term use of anti-psychotic drugs may be a concern or already may be causing “tardive dyskinesia” (permanent and abnormal involuntary movements);
    3. Where medications are causing “cognitive blunting” and lack of socialization progress;
    4. Where there is a complex picture of undesirable health problems, such as weight instability, poor appetite, eczema, and motor decline.
    5. Prospective mothers who are untreated need support to return to diet during pregnancy. If a woman is not on the diet at conception or shortly after becoming pregnant, the baby can have a variety of serious problems. These problems include microcephaly, cardiac anomalies, and mental retardation. The damage occurs because of in utero exposure to the mother’s elevated levels of PHE. It is a condition that is referred to as “Maternal PKU.” We recommend that pregnancy be deferred in all women with PKU until they are able to maintain a strict a strict diet during pregnancy.

    Our Positive Experience with Two Adults

    The two adults we treated (see Case Histories) have benefited significantly both behaviorally and socially. One adult also experienced improved health and motor ability. Observation of these adults in the community, at workshops, at physician visits, and at home, shows a PHE-restricted diet has enhanced their performance in everyday social and work life. Through these experiences, we also have learned that adults with PKU on the diet can take advantage of new training opportunities. The care providers for our two adults have been inspired by the adults’ increased socialization, endurance, and ability to focus their attention.

    Diet treatment also promoted more stable health and decreased skin eczema. Additionally, we were able to gradually eliminate antipsychotic medications. These medications operate to blunt cognition. In our experience, they promote untoward effects in the adult with elevated blood PHE levels.

    Finally, these two adults were at risk for losing residence in the community due to their difficult behavior. Stabilizing their emotional health through the diet gave them home-life security. It also had additional social and communication benefits. The outcome of more positive behavior and health in each of these adult’s lives has been dramatic. We believe that diet support will be beneficial throughout their lives.

    Overcoming Obstacles to Treatment: Obtaining Information, Guidance, and Support

    Obtaining adequate information

    . There is not much written for the adult population. Hopefully, these guidelines will prove invaluable in providing support for starting the low-PHE diet in your situation. Find and read as much as you can of the literature cited at the end of the guidelines.

    Finding professionals experienced in treating PKU

    . In addition to having involvement of the adult’s primary care physician and a registered dietitian in the facility, it is important to work with a metabolic treatment center in managing the diet. You can find such a clinic in your state by contacting the state health department. Almost every state has at least one treatment center (although a few less populated states may have “state-coordinated” treatment that makes use of PKU treatment consultants rather than having a center per se). Call them, explain your situation, and ask for their help and guidance. We cannot emphasize too much how valuable it is to have contact with a staff experienced in PKU treatment, whether or not they have experience with previously untreated adults.

    You can also receive support and information from companies that distribute the PKU medical formula (see PKU Medical Formula Products). The information we received from them encouraged us to start the diet and to decrease medications used for controlling the adults’ difficult behavior.

    Identifying Barriers and Assisting Staff and Family to Positively Embrace Diet Treatment.Because institutions are familiar and comfortable with using antipsychotic medications for controlling behavior problems, some of the staff may be resistant to trying the diet as a means of controlling these behaviors.

    Even with the information and support we received, our interest in starting the diet was met with some resistance. With persistence in making our case for trying the diet, we eventually received support from the residential facilities’ staff. We also had excellent support from the families. Because of the positive changes they saw occurring, throughout the early trying months of treatment, family members and day-to-day care providers supported the diet treatment and extra effort involved in creative meal planning.

    In our situation, both adults had family members outside their residence who were also conservators. We worked as a team with these family members. They provided extraordinary feedback about the adults and the comfort they themselves felt as the PKU adult achieved good control of blood PHE.

    We hope you can take advantage of our experience to make your own experience less time consuming and burdened by frustration. Managing the diet is not easy, but it can be a very rewarding experience for care givers, family and the adult involved.

    Starting and Maintaining the Low PHE Diet for Adults

    We present here an outline of the process we used to initiate and maintain dietary treatment for two previously untreated adults with PKU. We also include suggestions based on that experience. The guidelines focus on adults living in residential settings, but can be adapted for home situations.

    The Treatment Support Team

    The support team for an adult starting the diet ideally should include:

    • a nurse/genetic counselor
    • the residence physician and consulting metabolic specialist
    • the residence nutritionist and a metabolic nutritionist
    • the residence nurse
    • family members, who also may be conservators
    • care providers

    Plan to meet regularly as a team, providing in-service education, progress updates to staff and family, and training in response to any staff turnover. Be prepared for staff members to feel they are doing an injustice to a previously untreated adult because the diet is very restricted. They may have considerable empathy for the individual. Especially if they do not see changes right away, it can be frustrating to restrict the diet of an individual whom they may like very much. Emphasize the positive aspect of treatment: the diet is THE way to help this individual have the best chance for positive change and a better quality of life.

    Helpful Strategies to Reach Treatment Goals

    We cannot overemphasize the importance of ongoing communication among the treatment team and residential house staff members. This can be accomplished by regular training sessions, which also provide reinforcement to care givers. Patience is also necessary since results may not be immediate.

    Videotapes of the individual before and after treatment are useful illustrations of change for new staff. Changes in demeanor, behavior and physical appearance can dramatically demonstrate the value of the diet. Plan to videotape your own in-service training sessions to help with continuity when there is staff turnover. All new staff should be required to watch the “before-after” videos.

    Basic Diet Principles

    The goal of the PKU diet is to reduce dietary PHE intake to just the amount needed for normal physiological functioning, without any excess. (PHE is an essential amino acid, so it cannot be eliminated entirely.) This will cause a high blood PHE level to decrease to the desired range of 2-10 mg/dl.

    PHE is a component of all protein. It is found as a fairly constant percentage of protein. This means that any food containing a large amount of protein contains a large amount of PHE; foods with a small amount of protein contain a smaller amount of PHE.

    The PKU diet must include a medical product, usually consumed as a beverage. There are several brands available that are nutritionally suitable for adults. Each one has different amounts of protein, calories (energy), and other nutrients. The medical formula product provides most of the required daily protein, as well as calories (energy), vitamins and minerals. Without the PHE-free medical product, the diet is nutritionally inadequate.

    The diet also includes measured amounts of lower protein foods such as fruits, vegetables, and limited amounts of grain products; and PHE-free or nearly PHE-free foods such as special low protein products, and other foods that are mainly composed of fat or carbohydrate.

    All high-protein foods are usually eliminated from the diet to achieve blood PHE levels in the desired range. These include dairy products, eggs, fish, meats, poultry, legumes, and nuts. In some instances where the adult has a relatively higher tolerance for phenylalanine, very small amounts of the higher protein foods might be suitable for the diet, but this is not typical.

    The PKU diet involves a major change in eating patterns that have been established over a lifetime.

    Goals for Lowering Blood PHE Level

    Note: Throughout the manuscript, we indicate blood levels of PHE and TYR in “mg/dl,” (milligrams per deciliter) as is common in the US. Some laboratories, especially in Europe, use micromol/L (micromoles per liter.) For PHE, if the laboratory uses “micromol/L,” you can convert to mg/dl by dividing your number in micromol/L by 60. For example, 360 micromol/L = 6 mg/dl. Likewise, to convert mg/dl to micromol/L, multiply the number in mg/dl by 60 (for example, 8 mg/dl = 480 micromol/L). To convert TYR, divide micromol/L by 55 to get mg/dl, or multiply mg/dl by 55 to get micromol/L.

    Treatment Range

    At the beginning of diet treatment, our two adults had PHE levels of 31 mg/dl and 24 mg/dl, respectively. This is typical of off-diet adults with PKU; the range can be from the “teens” to over 40 mg/dl. Initially, our goal was to achieve PHE levels in the range of 3-12 mg/dl.

    The optimal blood PHE goal range for treatment in early-treated persons is 2-8 mg/dl (some would say 2-6 mg/dl). But in previously untreated adults, this degree of control may be difficult to achieve. Blood PHE levels even somewhat higher than 10 or 12 mg/dl may result in some positive changes. For example, in some cases, eczema appears to be responsive to lowering the blood PHE level below about 15 mg/dl. On the other hand, there is some evidence (from one case study report) that levels in the 2-6 mg/dl range may be necessary for maximum benefit even in previously untreated adults (see reference: Williams, K., Benefits of normalizing plasma phenylalanine: impact on behavior and health. A case report, J. Inher.Metab.Dis. 21, 1998, 785-790). For our two adults, we have kept the PHE level in the range of 2-10 mg/dl and continue to have positive results.

    Slowly Lower the Blood Phe Level

    For adults who have been on a normal protein diet, we believe it is most practical to bring down the PHE level gradually. A gradual transition to the PKU diet minimizes the possibility that the adult will reject the diet and maximizes the chances of long-term success. In some instances, the adult may accept the diet immediately, without a transition period. Then blood PHE levels can be lowered to ideal range within weeks; but this is typically not the case. Most people need to gradually accommodate to the very new way of eating that the PKU diet requires.

    Starting and Maintaining the Diet

    Biochemical Testing

    Baseline Biochemistry

    Before starting the diet, obtain a blood specimen from the adult and have it analyzed by a qualified laboratory for baseline PHE and TYR levels. This can be done at a PKU treatment center, or an outside lab that has the facilities for doing such analyses.

    Blood TYR levels can be low in untreated PKU. If TYR is low (less than 0.9 mg/dl), a TYR supplement can be started before making any diet changes. We found that a TYR supplement of 500 mg twice daily is an appropriate starting dose. Absorption can be poor, so crushing the tablets before giving them may help. This supplementation may need to be continued for some period of time even though the PKU medical formula product also contains TYR. All PKU medical formula products now contain tyrosine in varying amounts. In a normal person, 90% of ingested PHE is converted to TYR. In PKU, the PHE cannot be converted to TYR. Thus it is wise to monitor blood levels of TYR two to three times yearly. The normal level of TYR is approximately 1 mg/dl (55 micromol/L) and supplementation may be necessary when the diet treatment is more intensive. This is especially important during pregnancy.

    Biochemical Monitoring

    Plasma amino acid profile:

    We suggest that you consider doing a plasma amino acid profile before starting the diet. Thereafter, you can do this every six to twelve months if the staff has any concerns that the treated individual is getting inadequate amounts of protein in the diet from the PKU medical formula. If the profile appears stable after a year or two, consider monitoring only PHE and TYR.

    Other monitoring:
    Consider analyzing plasma for the trace elements selenium and zinc when the initial and monitoring amino acids are run. You should consider doing a CBC and chemistry panel at those times also. While selenium and zinc are supplemented in all of the “complete” PKU medical formulas that contain vitamins and minerals, serum levels can be lower than desired and supplements may be needed (especially selenium). This is something to consider, especially if you are doing a gradual transition to the PKU medical formula.

    PHE and TYR monitoring:
    After starting the diet, it is important to monitor PHE and TYR levels at least monthly, until the diet is well established.

    If the diet is planned properly and carefully maintained, and the recommendations of these guidelines are followed, you can expect a gradual reduction in blood PHE over a period of weeks or months. You may be able to discontinue the TYR supplement if you have used it, since TYR is supplemented in the PKU medical formula.

    Ideally, draw blood for PHE and TYR approximately two hours after a meal. This allows time for the blood PHE level to stabilize after a dietary PHE load from the meal. The goal is for postprandial levels to be maintained. Try to do the blood drawing at approximately the same time each time you do it, to avoid changes in blood levels due to diurnal variation. (The latter can vary as much as 2-3 mg/dl for blood PHE measurements.)

    Once the blood PHE level is confirmed to be in the recommended range on several tests, monitoring can be done less frequently (though monthly is still not too often to check the levels). We recommend a therapeutic range for serum PHE of 2-10 mg/dl. If you do not see positive results with levels in this range, consider trying to achieve tighter control in the range of 2-6 or 8 mg/dl. For TYR, we recommend a serum level of 0.9-1.8 mg/dl.

    Guidelines for Introducing the Diet

    General Approach

    To introduce the diet, we recommend the following general approach:

    Gradually introduce the PKU medical formula product, while decreasing high protein foods. As the adult begins consuming more of the recommended amounts of the medical product, decrease high protein foods further; eventually, eliminate them. As the blood PHE level drops toward the goal range, consider calculating PHE intake, rather than simply calculating dietary protein intake, for a more refined way to control blood PHE. It will be difficult to control the blood phe level effectively without counting dietary PHE. This is true if you are trying to achieve the lower range of blood PHE, and may be true for some individuals even when trying to control the PHE level in the higher range. Remember that each person will have a different tolerance for PHE; some will be more difficult to control, with considerable fluctuations, while others will be easier to control. This is due to the effect of different mutations in the PKU gene (there are over 200 genetic mutations that cause PKU).

    We attribute our success to a “gradual” approach. This slow process allows care providers and family to adjust to the new requirements and to gain confidence and skill in managing the diet. It also allows the adult to adjust to the new eating pattern. However, we have heard of some adults who have accepted the medical formula and diet changes immediately, without a transition period.

    It is essential to have guidance in planning the diet from a nutritionist, especially one experienced in PKU treatment. You will find a comprehensive guide to planning the diet from a 1997 publication, Nutrition Support Protocol for Previously Untreated Adults with Phenylketonuria (see Recipes and Diet Information). This is designed for use by a nutritionist. It presents very detailed, technical guidelines for calculating a PKU diet for adults; it does not give guidelines for gradual diet introduction, however.

    A practical plan for introducing the PKU Diet:

  • First, eliminate from the adult’s diet all cow’s milk (and other high protein liquids such as Ensure).
  • A normal (high protein) diet typically will contain enough protein after milk is eliminated. A nutritionist should confirm this as you start diet changes for a particular adult. Substitute an available nondairy creamer or cereal topping such as Rich’s Coffee Rich, CoffeeMate or Mocha Mix for the milk. Later, other high protein foods will need to be eliminated, as the PKU medical formula is consumed in quantities that provide sufficient protein.
  • Then choose a PKU medical formula product, from the array available.
  • Your choice of medical formula product should be based on nutritional needs and taste preference of the adult. Advice from a nutritionist familiar with these medical formula products will be very helpful. Each product has a slightly different taste, some more palatable than others. Periflex, by SHS North America, and Phenylade by Applied Nutrition, are two newer medical formula products that have a very acceptable flavor; others also may be used with success, such as Phenex from Ross Products. Applied Nutrition makes a good-tasting “candy bar” that contains the medical formula product; it can be used to augment the liquid form of the product. Applied Nutrition also has an Amino Acid Blend that can be added to foods to increase the protein intake without adding PHE. The Phlexy 10 system from SHS North America, which includes a powdered supplement, a “candy bar,” and capsules containing the medical formula product might be useful to consider also. One or more of the “modules” can be used, but you must take special care to provide vitamins/minerals.See PKU Medical Formula Products for a list of companies that distribute these products. A listing with basic nutritional information is also included in The Low Protein Food List for PKU and Low Protein Cookery for PKU (see Recipes and Diet Information. The nutritionists involved in planning the diet needs to determine the best PKU medical formula product or products to use for the particular situation.The volume of medical formula product that is required will depend on the particular brand that is chosen; those that are protein-dense and require only a small volume are low in calories (energy). If you are using one of these protein-dense medical formula products, you need to take special care to provide calories from low-PHE and PHE-free foods; weight loss due to inadequate caloric (energy) intake promotes muscle breakdown, with release of protein and PHE buildup in the blood.
  • Begin introducing the medical formula product as a flavored “shake.”
  • Add PHE-free “flavor maskers” Citrus flavors seem especially good at hiding the flavor. Or try something tangy like a combination of vinegar, herbs, and lemon. You also can add nondairy creamer for a creamy shake, and serve very cold, or even frozen or semi-frozen. Some people have found that eating pickles after drinking the supplement is very good at masking the aftertaste.Flavorings found to improve the taste of the medical formula product that add little or no extra PHE:
    • carbonated drinks such as Sprite, lemon-lime or Coke and coca-cola flavors
    • extracts such as vanilla, maple, mint or almond
    • drink mixers such as piña colada
    • concentrated juices such as orange or grapefruit
    • instant pudding mix, especially lemon
    • instant coffee or espresso
    • powdered drink mix such as Nestlé Strawberry Quik, Orange or Grapefruit Tang, or Kool-Aid
    • strawberry syrup
    • fresh fruit (e.g., bananas or strawberries), blending to make a smoothie
    • chocolate-flavor sauce (Try low PHE Almost Chocolate Sauce Mix from Dietary Specialties. See Low Protein Specialty Products)
    • granulated sugar

    Add any of these flavorings in desired amounts, even using several together. Be sure to avoid any product containing aspartame or the brand name Nutrasweet (which contains aspartame) , such as diet drinks, Equal table sweetener, and a whole array of reduced calorie foods. (Aspartame is composed of PHE and another amino acid.)

    Introduce the “shake” just a little at a time (even a teaspoon or tablespoon to start). Begin with one meal and gradually add the “shake” to other meals.

    Over time, encourage an increasing amount of the “shake” at each meal. Always give the “shake” with meals. This provides satiety and promotes absorption. It also promotes optimal protein synthesis. The medical formula product prescribed for the day should never be given all in one feeding. The human body needs to have protein distributed throughout the day for maximum metabolic benefit. Distributing the medical product over three or more feedings also will help to stabilize blood PHE.

  • As the medical product is accepted in larger quantities (e.g., an ounce or two at a each meal), a nutritionist needs to determine normal protein and calorie (energy) needs of the adult.
  • These nutritional needs are based on gender, weight and other factors such as activity level. Then the diet must be planned to reduce protein from food slowly, as use of the medical formula increases.Example:An adult may need 50 grams of protein daily based on their weight and age/gender. After the adult has learned to accept small quantities of the medical formula product, begin decreasing dietary protein intake other than milk. At this stage, the nutritionist might calculate the diet so that 10 grams come from the medical formula product and 40 grams come from foods.Over time, gradually keep reducing protein from the diet, increasing the amount that comes from the medical formula product. Ultimately, the adult’s intake of protein from natural food might need to be as low as 5 to 10 gm per day. (The actual amount will depend on the adult’s unique tolerance for PHE, which is determined by serial blood monitoring). In this instance, with 10 grams of protein coming from natural protein, 40 grams of protein out of the required 50 grams needs to come from the medical formula product.It is important to incorporate special low protein food products into the diet. Doing this will make it possible to keep decreasing the dietary protein intake from natural foods and still meet calorie and satiety needs. See Low Protein Specialty Products for ordering low PHE foods.
  • As the blood PHE level drops, consider calculating daily PHE intake from foods eaten (either as “exchanges” or as mg of PHE).
  • It is not easy to achieve blood PHE levels in the desired range without counting dietary PHE intake.To calculate PHE in the diet, you will need to use a food list giving PHE content of foods. The Low Protein Food List for PKU (1995) has a very comprehensive food list, containing nutritional information on several thousand foods available in the US. It is easy to use also.
  • After significant diet changes have occurred, monitor the treatment weekly; then monitor less frequently, as necessary.
  • The PKU nutritionist involved needs to make diet change recommendations based on blood levels and weight. Over time, the nutritionist will learn how much PHE must be decreased or added to achieve the desired blood level for that particular individual. Generally, if the level is just slightly too high or low, a change of as little as 30-50 mg of PHE per day can make a difference in the blood PHE level.(Both adults with whom we have experience were initially monitored weekly by a consulting registered dietitian. This Northern California rural area does not have a local nutritionist familiar with PKU. We continue to have ongoing nutrition services twice a month for blood monitoring, for review of diet, and for making diet adjustments. This is funded through the residence and the Regional Center. Regional Centers in California are state-funded and provide services to all developmentally disabled persons.)
  • After an ideal blood PHE level has been achieved, continue to monitor the diet and make adjustments in PHE and calories (energy) as needed to maintain good blood PHE control and normal weight.
  • Don’t expect the blood PHE level to remain perfectly stable once you reach your goal. Be aware that the level can “bounce around” considerably, even when the diet remains very constant. Onaverage, try to maintain the level in a good control range of 2-10 mg/dl. 
    Other Hints for Managing the Diet

    • Incorporate into the diet the special low protein pastas, breads, crackers, cookies, sauce mixes and other products that are available by mail-order (

    see Diet Resources).

    This is very important for variety and calories (energy) in the diet. You also can make your own baked goods using the special low protein “flour” mixes. A bread machine is invaluable for making your own fresh low protein breads; it has been essential for us in managing our two adults. There are several excellent cookbooks of low protein recipes for the PKU diet; these also are essential.Low Protein Bread Machine Baking for PKU has recommendations for bread machines and excellent recipes. The Low Protein Food List for PKU and Low Protein Cookery for PKU also are diet management essentials (see Diet Resources).

  • Become familiar with vegetarian cooking.Vegetarian recipes will give you ideas for new and unusual ideas you can incorporate into the diet. (For one adult, we used mustard and ketchup in large quantities to flavor the low protein pasta as it was introduced!) National PKU News also shares recipes and diet tips (see Diet Resources), and recipes often are shared on the PKU Listserv Internet group (see Diet Resources).
  • Consider using a two or four-week cycle menu to ease the burden of diet planning.
  • Small adjustments in PHE or calorie (energy) intake can be made once the basic menu is established, as blood monitoring or weight alterations in the adult indicate the need for change.
  • Use a variety of teaching tools to assist staff in maintaining the diet.
  • These include teaching tools such as PKU for Children Learning to Measure (seeRecipes and Diet Information), videotapes for in-service diet teaching sessions, and color code menus to make the diet easier to manage for care providers.
  • Read the literature that pertains to adults who have received late-treatment (seeReferences).
  • It is helpful also to read literature from the medical formula product companies. You can obtain this information by writing or calling the companies (see PKU Medical Formula Products). It is important to familiarize yourself with as many aspects of PKU treatment as you possibly can.Diet Precautions
    • Lower blood PHE levels using established principles

    To reduce blood PHE levels to the desired therapeutic range, remember that these important elements of treatment MUST be included:

    1. Correct calculations of the adult’s dietary protein and energy needs must be made by a nutritionist.
    2. The diet must be planned to account for the individual PHE requirement, determined over time by blood monitoring.
    3. The medical product must be included in adequate amounts on a daily basis, preferably divided into three or more servings.
    4. Diet changes must be based on serial blood monitoring and weight monitoring.
    5. Avoid aspartame in food and drugs

    As previously mentioned, persons on the PKU diet need to avoid consuming aspartame. Be aware that various foods and medications in liquid and solid form can contain PHE in the form of aspartame (commonly found as Nutrasweet in foods and medicines). Don’t hesitate to call pharmaceutical companies if you have questions about whether a drug, vitamin/mineral supplement or medicine contains aspartame. There is a list of medicines containing phenylalanine on the National PKU News Web site (pkunews.org). The label on foods should clearly indicate the inclusion of aspartame or Nutrasweet. Diet drinks or diet foods often contain aspartame or Nutrasweet.

  • Avoid too low blood PHE levels
  • Avoid blood PHE levels below 2 mg/dl. Prolonged low levels (not a single low level) can cause a variety of medical problems, including irritability, weight loss, and seizures. Also, laboratory analyses when PHE levels are 2 mg/dl and lower are less reliable if the Guthrie Test is used for monitoring. When the levels are above 20 mg/dl, the accuracy is also less using the Guthrie Test. Other monitoring techniques are more precise (McCaman-Robins Fluorimetric Technique, using an Amino Acid Analyzer, etc.) and are recommended. Liberalize PHE in the diet slightly if low levels occur (adding as little as 30-50 mg PHE may be sufficient), or reduce PHE in the diet if you continue getting PHE levels that are too high.
  • Avoid too low blood TYR levels
  • Avoid blood TYR levels below 0.9mg/dl. Add a TYR supplement as needed (for further discussion of TYR, see Biochemical Monitoring). Managing IllnessThere will be times when the on-diet adult will have a cold, flu, or other illness. Incorporate fluids with calories (energy) in any way you can (i.e. juices, Jell-O, Jell-O as a liquid, and sodas without aspartame or Nutrasweet) until the illness resolves.You may need to dilute the medical formula product (for example, to 50% strength), or even stop it temporarily in times of stomach flu or intolerance. During periods of illness, remember that no matter what you do, the PHE levels will increase somewhat. This happens as a result of the body’s response to illness, which involves breakdown of body protein. Keeping a good intake of calories (energy) will help prevent the breakdown of protein for energy, serving to ameliorate a rise in blood PHE. Some clinics recommend reducing the dietary PHE intake slightly (for example, 20-30% less), but there is no evidence that this will prevent a natural illness-related increase.Both of our adults have experienced episodes of illness or had surgery, and returned to health while still on the diet. In these periods, we did extra blood monitoring of PHE, TYR and trace element levels to determine any interplay with the illness. We did a chemistry panel, PHE, TYR, zinc, selenium, biotin and carnitine, and ended up supplementing biotin and carnitine due to low blood levels.

    Persistence is the Key

    After the adult’s blood PHE levels are lowered to the desired range, you may quickly notice positive changes (within days or weeks)—or you may not notice any significant changes for months. It is important to remain optimistic and continue the diet despite lack of immediate or obvious change. PHE is a toxin for the central nervous system. When that toxin is removed, there is a very good chance positive changes will occur. These changes can take time; do not get discouraged!

    Other Treatment Considerations

    Antipsychotic or Major Tranquilizer Medications

    If an adult with PKU has high blood PHE levels, he or she generally will not benefit much from antipsychotic medication. This is in part because the elevated blood PHE and low TYR levels effect neurotransmission in the central nervous system.

    Antipsychotic medications not only work inadequately in individuals with PKU, but can cause a deterioration in skills. They should be used with great caution. Changing any drug quickly, however, can cause deleterious withdrawal effects. One investigator also has reported an increased sensitivity to medication for seizures as PHE levels decreased in one adult.

    Fortunately, there is increasing agreement that when treating adults with PKU, antipsychotic medications should be used only as a last resort. But physicians, nurses, counselors, and nutritionists may not feel convinced that starting the diet can be as beneficial as keeping an untreated adult on antipsychotic drugs. With both of our adults, we were fortunate to have consultation from a psychiatrist who was knowledgeable about current theories of medication use that promoted individual medication management during the transition to diet. We believe that his knowledge regarding the effects of drug therapy was helpful in managing withdrawal of the medications used in treating our two adults.

    Fading medication for behavioral or emotional support may not be the highest priority in your PKU treatment approach. However, after the diet is started, consider gradually eliminating drugs under the careful supervision of the primary care physician if there is clearly no benefit from them or if you note any side effects or worsening of behavior. If the adult accepts the diet and you see improvement in behavior or in other areas, consider fading the medication, with 10% reduction at a time. You may need to fade the medication over a period of months to avoid withdrawal dyskinesia.

    Behavioral Support and Controlling Anxiety

    Behavioral Support

    Care providers sometimes describe untreated persons with PKU as having “behavior problems” when a large component of what the adult is experiencing is anxiety. Even many adults with PKU who are early-treated and of normal intelligence will experience anxiety when they go off the diet and have chronic high blood PHE levels. This anxiety is not within their control; it is due to the effects of PHE on the central nervous system. Behavioral support to assist the individual in focusing on needed tasks, and redirecting their attention away from the anxiety, is crucial for their social success. Positive behavior support is based on the premise that “behavior is communication.”

    Controlling Anxiety

    There is information in the scientific literature about using anti-epileptic medications to reduce anxiety and stabilize mood. We used one anti-epileptic drug, valproic acid, before beginning the diet in one adult. If you believe such an approach would be helpful, we recommend that you do a CBC and assessment of liver function at baseline and during follow-up. This medication for one adult worked in the transition period. If you use this drug, serum carnitine should be carefully monitored and supplements given if you identify a deficiency.

    Buspirone was a drug we have used to support the other adult. She also was on Haldol, Lorazepam and Trazadone before starting diet treatment and was weaned from these prior to the diet. After years on Buspirone, the drug is being weaned by dropping one of the three doses per day each month until it is stopped entirely.

    Changing Attitudes about Food

    Remember that food is a part of life for all of us. Food also may have been used as a reinforcer in the adult’s life to quiet, appease, or motivate. Food restrictions and diet changes mean changes in long-held personal associations. The restrictions and changes in eating patterns can feel like a loss in the way both the staff and family are accustomed to relating to the adult. If care providers do not acknowledge these changes or find new ways to communicate, the altered associations with food can make it much more difficult for the adult to adapt to the diet.

    Costs and Benefits of Treatment

    The costs and benefits of treatment are important to consider. The PKU diet is expensive, and paying for it usually requires help from the state and/or insurance. But compare treatment costs to the theoretical cost that might have been incurred if the adult had not been treated.

    In our situation, for instance, we could compare the cost of treatment versus hospitalizing one of the adults. For the other adult, we could compare treatment cost versus putting her in a more restrictive facility. In most cases, the cost of treatment is less than the extra care taking required when the adult is not treated. But the true benefit is the less tangibly measured improvement in quality of life that can come about for the treated adult.

    All states and countries are different in their financial support of treatment for adults. In California at the time this is being written, the medical formula products are funded by private insurance and the Genetically Handicapped Persons Program (GHPP). Medi-Cal, with a Treatment Authorization Form, may need to be approached first (this program may deny coverage and refer a prescription to GHPP). To find out what assistance there is in your state for adults, contact the State Health Department or a PKU treatment program. An increasing number of states in the US have legislation mandating insurance coverage of the medical formula products. Some legislation also covers special low protein foods. However, there may be an age limit to the coverage of formula or food or both.

    To obtain financial support for PKU treatment through a state-supported program or insurance, be prepared to provide clear, written support material (for example, details of diagnosis, goal of diet, and expected result).

    The PKU medical formula product can cost up to $4,000 or more per year, depending on which product you choose. Additionally, special low protein foods, which are not on the regular menu of the house, can cost another $1,000 or more per year. The monthly cost may average about $450 (in 1998). You also may need to add a budget for the nutritionist’s dietary work if you are hiring a consultant. We found that planning a four-week cycle menu required about 15 hours of time.

    Considerations of Aging

    Don’t forget to consider normal aging needs of the adult, such as calcium or estrogen replacement therapy for postmenopausal women, etc. Both adults were born in 1935 and started the diet in 1992 and 1993. Regular medical care of other complicating problems such as heart, lung and renal disease is commonly needed in an aging population and should be anticipated.source

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