Barbara E. Dolan, RN, MSN
Nurse Counselor for Genetics, Redwood Coast Regional Center, Ukiah, CA
Richard 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
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.
- 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
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
- Case Histories: Two Adults with PKU
- Sample Menus (will be available at a later date on the PKU News web site)
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:
- 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:
- inability to sit
- sleep disturbances
- 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
- self-injury and self-mutilation
- autistic-like behavior
- mental retardation
- muscular hypertonicity or hypotonicity
- whole body repetitive movements
- spastic paraplegia, quadriplegia or tetraplegia
- 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”
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).
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:
- Where multiple medications have been unsuccessful in controlling agitation and/or screaming;
- 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);
- Where medications are causing “cognitive blunting” and lack of socialization progress;
- Where there is a complex picture of undesirable health problems, such as weight instability, poor appetite, eczema, and motor decline.
- 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.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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. On average, try to maintain the level in a good control range of 2-10 mg/dl.
- 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 (see Recipes 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 (see References).
- 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.
- 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:
- Correct calculations of the adult’s dietary protein and energy needs must be made by a nutritionist.
- The diet must be planned to account for the individual PHE requirement, determined over time by blood monitoring.
- The medical product must be included in adequate amounts on a daily basis, preferably divided into three or more servings.
- Diet changes must be based on serial blood monitoring and weight monitoring.
- 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).
There 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.
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
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.
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.”
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.
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.
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.
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.
- Baumeister, A., and Baumeister, A. (1998) Dietary treatment of destructive behavior associated with hyperphenylalaninemia, Clinical Neuropharm-acology, 21: 18-27.
- Brown, M.C.J. and Guest. J.F. (1999) Economic impact of feeding a phenylalanine-restricted diet for adults with previously untreated phenylketonuria, J. of Intellectual Disability Research, 43: Part 1, 30-37.
- Calabrese, J. and Delucchi, G. (1995) Spectrum of efficacy of valproate in 55 patients with rapid-cycling bipolar disorder. American Journal of Psychiatry, 147: 431-434.
- Harvey, E.L. and Kirk, S.F. (1995) The use of a low phenylalanine diet in response to the challenging behavior of a man with untreated phenylketonuria and profound learning disabilities, Journal of Intellectual Disabilities Research 39: Part 6: 520-526.
- Jefferson, J.W. (1993) Mood stabilizers: a review. From Current Psychiatric Therapy, ed. Dunner, D.L., W.B. Saunders Company, Philadelphia, 245-254.
- Koch, R., Azen, C., Friedman, E.G., Fishler, K., Baumann-Frischling, C., and Lin, T. (1996) Care of the adult with phenylketonuria. European Journal of Pediatrics, 155 (Suppl. 1), S90-S92.
- McCombe, P.A., McLaughlin, D.B., Chalk, J.B., Brown, N.N., McGill, J.J. and Pender, M.P. (1992) Spasticity and white matter disease in adult phenylketonuria, Journal of Neurology, Neurosurgery and Psychiatry, 55: 359-361.
- Potocnik, U., and Widhalm, K. (1994) Long term follow-up of children with classical phenylketonuria after diet discontinuation: a review. Journal of the American College of Nutrition, 13 (3): 232-236.
- Schuett, V. (Winter 1997) Off-diet young adults with PKU: lives in danger, 8(3): 1-3, Schuett, V. (Fall 1996) Can PKU treatment be improved? Vol. 8, No. 2:1-3, National PKU News.
- Scriver, C.R., Kaufman, S., and Woo, S.L.C. (1995) The hyperphenylalaninemias. In (eds.) Scriver, C.R., Beudet, A.L., Sly, W.S., and Valle, D. The Metabolic and Molecular Bases of Inherited Disease, New York, McGraw-Hill, Inc., Vol. 1: 1015-1075.
- Villasana, I., Butler, J., Williams, J.C., and Roongta, S.M. (1989) Neurological deterioration in adult phenylketonuria, Journal of Inherited Metabolic Disease, 12: 451-457.
- Waisbren, S.E. and Levy, J.L. (1991) Agoraphobia in phenylketonuria, Journal of Inherited Metabolic Disease, 55: 755-764.
- Williams, K. (1998) Benefits of normalizing plasma phenylalanine: impact on behavior and health. A case report, Journal of Inherited Metabolic Disease, 21: 785-790.
- Yannicelli, S., and Ryan, A. (1995) Improvements in behavior and physical manifestations in previously untreated adults with phenylketonuria using a phenylalanine-restricted diet: a national survey, Journal of Inherited Metabolic Disease, 18: 131-134.
- Yule, K. Schmidt (1996) Phenylketonuria. From: Primary Care of the Child with a Chronic Condition, ed. Jackson, P.L. and Vessey, J.A., Mosby Year Book, Inc., 2nd ed., St. Louis, Chapter 29:623-649. (Third edition is in press.)
Acosta, P.B., and Yannicelli, S., third edition (1997) The Ross Metabolic Formula System Nutrition Support Protocols, Ross Products, Division of Abbott Laboratories, Columbus, OH 43215-1724. (See PKU Medical Formula Products for additional contact information.)
Acosta, P.B., and Yannicelli, S. (1997) Nutrition Support Protocol for Previously Untreated Adults with Phenylketonuria, Ross Products, Division of Abbott Laboratories, Columbus, OH 43215-1724. (See PKU Medical Formula Products for additional contact information.)
Feucht, S. and Trahms, C. (1992) PKU for Children Learning to Measure. Nutrition Section, Clinical Training Unit, Child Development and Mental Retardation Center, University of Washington, Seattle, WA 98195.
National PKU News (1989-present), ed. Virginia Schuett, National PKU News, 6869 Woodlawn Ave., N.E. #116, Seattle, WA 98115. For a one year subscription to the newsletter, send check payable to National PKU News: $18 US residents; $22 US for Canadians, $28 US for foreign subscription (drawn on a US bank or US currency). No purchase orders accepted.
National PKU News Web site (contains a large amount of regularly updated information about PKU, diet and diet resources): pkunews.org
PKU Listserv group on the Internet. This is a large group of families and professionals who share recipes, diet management tips, and other information about PKU. To join, send an e-mail to: email@example.com.
Schuett, V (Winter 1998) Aspartame in drug products, in National PKU News, 9(2):7. (See the list of medicines containing Phenylalanine.)
Schuett, V. (1993) Low Protein Bread Machine Baking for PKU, Dietary Specialties, Inc., 865 Centennial Ave., Piscataway, NJ 08854. (See Low Protein Specialty Products for additional contact information).
Schuett, V. (1997, third edition) Low Protein Cookery for PKU University of Wisconsin Press, distributed by Chicago Distribution Center, 11030 S. Langley Ave., Chicago, IL 60628. (Tel: 1-800-621-2736).
Scientific Hospital Supplies, Inc. (1992) International PKU Recipe Book, eds. S. Barton and P. Portnoi, Scientific Hospital Supplies, Inc., P.O. Box 117 Gaithersburg, MD 20884. (See PKU Medical Formula Products for additional contact information.)
Yannicelli, S., Davidson, A.J., and van Doornick, W. (1990) Diet Intervention for the Late-Treated Adult with PKU, Inherited Metabolic Disease Clinic, University of Colorado Health Sciences Center, Campus Box C-233, 4200 East Ninth Avenue, Denver, CO 80262.
Applied Nutrition, Inc.
273 Franklin Ave.
Randolph, NJ 07869
Tel: 1-800-605-0410 or 973-361-7004
Web site: www.MedicalFood.com
Mead Johnson and Company
2400 W. Lloyd Expressway
Evansville, IN 47721-0001
Tel: 1-800-457-3550 or 812-429-6399
Web site: www.meadjohnson.com/metabolics
Ross Products Division
625 Cleveland Ave.
Columbus, OH 43215-1724
Tel: 1-800-227-5767 or 614-624-7677
Web site: www.pedialyte.com
SHS North America
PO Box 117
Gaithersburg, MD 20884
Tel: 1-800-365-7354 or 301-315-5500
Web site: www.shsna.com
(Available through mail-order only.)
Dietary Specialties, Inc.
865 Centennial Ave.
Piscataway, NJ 08854
Tel: 1-888-636-8123 or 732-980-6700
Web site: www.menudirect.com
Ener-G Foods, Inc.
PO Box 84487
Seattle, WA 98124-5787
Tel: 1-800-331-5222 or 206-767-6660
Web site: www.ener-g.com
Kingsmill Foods Company, Ltd.
1399 Kennedy Rd. Unit #17
Canada M1P 2L6
Web site: www.kingsmillfoods.com
3600 Holly Lane North, Suite 80
Plymouth, MN 55447
Web site: www.med-diet.com
SHS North America
PO Box 117
Gaithersburg, MD 20884
Tel: 1-800-365-7354 or 301-315-5500
Web site: www.shsna.com
Cambrooke Foods, Inc.
PO Box 5473
Wayland, MA 01178
Web site: www.cambrookefoods.com
The two adults for whom we initiated PKU treatment were identified through genetic and psychiatric clinics for different reasons:
- The first adult’s decline in health warranted attention; the origin of her developmental disability was unknown. Her screaming behaviors and agitation also were extreme.
- The second adult, known to have PKU, received little benefit from antipsychotic drugs to control agitated behavior.
The First Adult with Late Treatment
The first adult was born in 1935, and diagnosed with PKU in 1992 when she was 57 years old. She was born in a small town in northern California and is an only child. At three years of age, the parents realized she was delayed compared to their own nieces and nephews. They sought medical evaluations in 1938 because she was not walking well nor learning like her cousins. Medical reports reveal that two physicians ruled out pituitary and endocrine disorders. (PKU was first discovered in 1934, but widespread diagnostic techniques were not available until many years later).
The adult reportedly received radiotherapy. Coincidentally she began walking more steadily. She exhibited few language skills (mostly with music), but had communication skills to direct her parents to her needs. She could understand simple instructions.
She remained at home until 1983, when she was 47 years old. Then she was placed in a developmental center in southern California. She was there for approximately seven months. Her conservator remembers the parents being told that she did not fit in; reportedly, she spent time alone, was unhappy, and did not socialize. She returned home without being given an etiology for her developmental disability.
In 1985, when they were in their 70’s, her parents again sought residential support. What was known about her included the following: she was prone to weight loss in response to illness; her weight gain could be exponential in times of wellness; she was borderline diabetic; she had a chronic, strange musty body odor; she was plagued with body rash, sun sensitivity and eczema; she had no speech; and she was considered autistic.
In December 1990, her residential care provider of five years gave notice to have her moved from that home due to behavioral problems. She moved to an ICF/DD-H (a residence with five other developmentally disabled adults). A nurse and physician were available for her health needs. Unfortunately, her daily aggression, self-injury, and screaming behaviors greatly restricted her from all participation in community outings from this facility.
In 1990 she was referred by her residence physician for evaluation of psychotropic medications, for psychiatric follow-up in our local clinic staffed by San Francisco specialists. Her weight had increased from 140 pounds in 1986 to 162 pounds in September 1990. Medication included Diazepam to calm her for medical procedures and thioridazine for behavioral management. The goal was to find a balance of medication management for her screaming and self-injury behaviors. However, this was not attained even with the medication. Medication trials and support for behaviors and poor sleep began. Medications included Bupropion, Diazepam and Lorazepam. Bupropion provided no benefit for her screaming and agitation. Diazepam was tapered, and she was begun on Trazodone. Lorazepam and Trazodone were the chosen medications to remain in place because these drugs did assist in reducing her screaming. The doses were adjusted to correct ataxia, drowsiness, and negative effects on appetite.
Quarterly psychiatric follow-up continued through all of 1991 to monitor medication outcome. Her screaming continued through medication trials until Trazodone was increased in September 1991. With screaming behaviors controlled by medication, she began a steady trend in weight loss. By spring 1992 she had lost 40 pounds.
In the residence, she was started on high calorie, high protein supplements to address the problem of weight loss, but she failed to gain back the desired weight. She was mentally alert with medication support. Still, she continued pacing, could not tolerate touch, was failing to do tasks she previously was capable of, and was highly agitated. She also began a pattern of frequent falling.
She was weaned to a lower dose of Trazodone with the thought that it was contributing to her falling. Buspirone was started to help deal with her anxiety and agitation, with hopes of improving her appetite and ataxia. Her screaming became less frequent, but she looked gaunt and she was unable to walk without two-person assistance. She was tremulous, appeared frightened, and displayed extreme anxiety. On examination the local physician found nothing to explain the cause of her decline. Trazodone, Lorazepam and Buspirone were continued for another four months and were ruled out as a cause of decline by her physician and her psychiatrist.
Her falling continued. Her weight loss overall was 50 pounds in a 12-month period. She had rashes that would not go away. She appeared to be aging, with thinning hair, yet she had more facial hair. She was alert, but markedly agitated. Her motor skills were declining. She was referred from the psychiatric clinic to our genetics clinic for an evaluation of her physical appearance and behavioral features.
Due to her birth prior to newborn screening (1966 in California), her fair skin and hair, her presenting behaviors, and poor health, the Nurse Counselor for Genetics was suspicious she might have PKU. A blood PHE test was done along with other blood chemistries to identify the cause of her decline. PKU was confirmed and diagnosed. The diet was not started until we did urine testing to rule out a related disorder, biopterin deficiency. She was 57 years old.
After the diagnosis of PKU, the referring Nurse Counselor for Genetics and the residence nutritionist (authors Barbara Dolan, RN and Christina Bekins, RD, respectively) sought resources by contacting various metabolic centers across the country. We obtained by mail from The University of Colorado, “Diet Intervention for the Late-Treated Adult with PKU” (Yannicelli et al, 1990). This publication opened our eyes to considering diet treatment. This center also told us that medications would be inadequate at controlling her behavior because neurotransmission was influenced by the buildup of blood PHE.
We found that studies on adults with PKU existed, but information about how to begin treatment was mostly limited to children. Our inquiries brought responses from consultants in metabolic and newborn screening centers. We contacted the manufacturers of PHE-restricted medical products and obtained additional support to start diet treatment. We felt the possible benefit of the diet was a valid reason to attempt it, even for an older adult.
Starting the PKU Diet
Due to our concern about the adult’s acceptance of the diet, her declining motor skills, and the risk of placing her out of her community home, our plan had several goals:
- to reduce the medications that were not benefiting her;
- to begin TYR supplementation due to a low blood TYR level; and
- to slowly introduce the medical product and PHE-restricted diet to lower blood PHE.
Outcome of Treatment
This adult now has been on a PHE-restricted diet since 1992. Her current PHE level is in our goal range. Strict diet calculations of protein were used to create menus. We have monitored her PHE and TYR levels and provided a selenium supplement due to low blood selenium levels.
Her appearance has changed remarkably since starting treatment. She is now an adult with “bloom” in her cheeks. Her social skills have increased, and she has become a visitor/companion in a convalescent hospital. She has no speech, but learned to interpret the sign for bathroom, and communicates personal care and medical needs by vocal sounds. Her ataxia disappeared after six months on diet. Her motor endurance improved as well. Her weight remains in her goal range, from 130-135 pounds. After four years on diet her hair darkened (a result of increased melanin production due to the lowered PHE level). Her appetite does vary. Food preferences include dislike of fruit juice and sweets but she likes sour and tart foods. She likes pastas, but dislikes many of the special low protein breads and muffins. She always has consumed all required medical formula product.
Her screaming behavior did not return after we weaned her from Lorazepam and Trazodone and introduced diet. We continued anxiety medication.
TThis adult now is more socially comfortable, loves going out to eat, and rides in the car for outings and field trips. Her family sees her as the healthiest, the most comfortable, and the happiest she has ever been. They remain very impressed by her social and communication gains. Though she remains nonverbal, she knows cause and effect and can initiate her wants clearly. Medical monitoring includes addressing dental and aging issues.
The Second Adult with Late Treatment
The second adult also was born in 1935 and also is an only child. As a growing child she remained at home until she was eight years old. There were no local school special education services available. Her parents placed her in a northern California school for special children to ensure enrichment. She spoke single words at two and three years of age. Her first sentence at eight years of age was stay and play at the lady’s house.” Because of behavioral challenges as a young adult, she required placement in a California developmental center from 1966 to 1982. It was here that her diagnosis of PKU was made.
Her parents were told then that the diet would not help her mental retardation. Consequently, she was not started on treatment. Upon discharge from this facility, she returned home with her parents where she remained from 1982 to 1993. During this time at home, she did have a considerable time out-of-home for both respite care in a family setting and in day program attendance.
In 1983, her behavior worsened and necessitated starting daily Thioridazine. The Regional Center nutritionist suggested dietary treatment for her behaviors. At that time, a PHE-restricted diet for adults was considered experimental by many specialists. However, results from the Maternal PKU Collaborative Study revealed that diagnosed adults who were part of the study reported feeling much better on dietary treatment. The nutritionist was comfortable with the diet and identified this adult as possibly benefiting from treatment.
A rapid phase-in trial of a PKU medical product was tried. By parent report, the staff had poor interest, food preparation was inadequate, and no PHE monitoring was done. The adult experienced a 20-pound weight loss. During this trial, she developed sudden signs of tardive dyskinesia, facial tics, twitching, severe tremor, and physical discomfort. The diet was stopped due to these side affects, and the Thioridazine was replaced with another medication. The primary physician and parent concluded the diet caused the heightened side effects of the medication as well as poor health.
This adult continued to live at home during the following years, but resided in respite care facilities to help the parent. In 1992 this adult developed behavioral problems that began another escalating cycle. The cycle of behaviors did not appear to be linked to the menu in the respite facility (this facility served a heavy meat menu). They gave notice to the adult to move due to her screaming and aggressive behaviors. To manage these behaviors, she was followed in a psychiatric clinic. Since she was treated for hypertension, trials of Propranolol were attempted as a calming agent, but the Propranolol did not control her hypertension.
Buspirone was given a trial but it did not help her anxiety and agitation. In 1993, the parent agreed to residential placement. However, the additional focus on her behavior did not improve her screaming and the aggressive behavior.
Starting the PKU Diet
The nurse for the new residence worked closely with the authors of these guidelines. He was aware of the benefits of dietary PHE restriction for the first adult in this report. The nurse requested consultation from us for beginning diet treatment. This adult had behaviors of screaming, aggression, agitation, anxiety, and skin picking. These symptoms did not improve after restarting Haloperidol nor after trying other programs. Antipsychotic medication for controlling her behaviors also was beginning to have undesirable effects.
Starting the diet was not so simple, however. This adult was higher functioning than the first adult and enjoyed talking and socializing. Her conservator parent was reluctant to impose diet for two reasons: First, the experience of the 1983 diet; and second, she wanted assurance we had tried all other approaches to improve the adult’s behavior stability. To consider diet treatment for this adult, we provided the following support:
- We wrote a letter to the primary physician outlining the potential benefits of diet treatment for adults who were untreated. This letter was in the form of an abstract of our current knowledge and experience.
- In tracking medication trials to control this adult’s screaming (including Thioridazine, Propranolol, Lorazepam, Buspirone and finally, Haloperidol) we concluded that medication alone resulted in consistently poor benefit and untoward effects.
- We gave the parent more information about PKU and current treatment experience. We gave the parent support. Though the diet was complicated, we assured her it would be tailored to her daughter’s tastes, and that it would be provided for behavioral support.
- We took a complete history, including a review of early memories, family history, and pedigree information. These provided a forum for planning with the parent.
- We assured the parent we would proceed slowly. We assured her we would keep in mind the current use of an antipsychotic drug and wean that medication, if possible, to utilize an antianxiety medication.
- Finally, we also assured the parent we would treat the low TYR level with a supplement prior to starting the diet.
- The parent agreed to first start valproic acid as a mood stabilizer before starting diet. We gave carnitine supplements due to already low serum levels. We used anti-epileptic medication as a mood stabilizer, which brought some diminishing of the adult’s anxiety.
Outcome of Treatment
This second adult has been on the diet since October of 1993. She was given valproic acid for anxiety until June 1994. At that time, she became very ill with what was considered to be a viral infection. Elevated liver function tests required the drug to be discontinued; however, at this point she already was on a full PHE-restricted diet. She continued on the diet through this 30-day illness. She recuperated well, without return of untoward behaviors. Her liver enzymes also returned to normal.
This adult is fully participating in taking a PKU medical formula product, low protein foods and a TYR supplement. Initially, we provided extra selenium in her diet because of extremely low levels. The drop in selenium was a consequence of decreasing her natural protein intake. This occurred in both adults. Later, transition to a different medical formula product provided adequate selenium without supplementation.
Based on personal contact, as well as contact with the care provider and family, the adult’s screaming behavior abated and has recurred rarely. Eczema outbreaks and scratching are infrequent. Her blood PHE levels have been in the goal range; she shows improvement and stability even with blood PHE levels slightly out of the desired range.
When there are disappointments, transitions or changes in this adult’s life, she now is more open to comforting communication. In the past, she would have escalated from a tantrum to dangerously throwing items and being aggressive toward other people. Her anxieties about events and anticipations are reduced, and she listens to explanations. Her speech articulation is clearer, and her extended family reports she is more understandable in a flow of conversation. There is a plan to make more real work available to her. This will allow her to spend more time in the community and to interact with more people.
the model presented here for our support of these two adults is one we believe can be considered for other previously untreated adults. This project was made possible through the clinical support and expertise of Dr. Richard Koch. Based on our experience, we support a diet transition for adults that is individualized, based on clinical information as well as food likes and dislikes of the adult. We emphasize the importance of a slow transition to the full PKU diet.
We would be happy if you would like to contact us regarding your experiences and challenges in caring for previously untreated adults with PKU. We are very interested in adding to and revising our guidelines based on the experiences of others. Please contact Barbara Dolan, RN, MSN:Barbara Dolan, RN, MSN
Nurse Consultant for Genetics
Redwood Coast Regional Center
1116 Airport Park Blvd.
Ukiah, CA 95482
Tel: (707) 462-3832 ext. 242
Fax: (707) 462-3314