for children with special health care needsfor children with

NutritionJuly/August 2013

INTRODUCTIONPhenylketonuria (PKU) and hyperphenylalaninemia

(HPA) are metabolic disorders that affect an enzyme re-quired for the conversion of phenylalanine to tyrosine, leading to a build-up of the amino acid phenylalanine (Phe) in the blood. Increased blood levels of Phe are associated with negative neurologic outcomes, including intellectual disability. These negative outcomes are preventable with treatment that includes the restriction of Phe in the diet.1,2 PKU and HPA are optimally treated by an interdisciplin-ary team that addresses the nutritional, medical and social aspects of the condition.

EtiologyPKU and HPA are both inherited metabolic diseases, a

class of genetic disorders usually caused by mutations in enzymes necessary for metabolism. Both conditions are inherited in an autosomal recessive pattern, meaning both parents must be carriers of the gene that causes the mutated enzyme. See Figure 1.

The incidence of PKU varies among different ethnic groups, as shown in Table 1 on page 3. A genetic counselor, as part of the interdisciplinary team, can assist families in determining the risk of having another child with PKU, or of a family member being a carrier.

PKU is caused by a deficiency of phenylalanine hydrox-ylase (PAH); reduced PAH activity decreases the body’s ability to break down the amino acid phenylalanine (Phe), leading to increased Phe in the blood. Some individuals have residual PAH function; resulting in a more mild eleva-tion of blood Phe levels called HPA. See Figure 2.

Volume 28, No. 4

Phenylketonuria (PKU) and Hyperphenylalaninemia (HPA) – A ReviewSarah Bailey, MS, RD, CDClinical DietitianOlympic Medical CenterPort Angeles, WA

CENTER ON HUMAN DEVELOPMENT AND DISABILITY, UNIVERSITY OF WASHINGTON, SEATTLE, WASHINGTON

The exact mechanism of the neurological damage caused by untreated PKU is unknown. Phe is a precursor of tyrosine, and dopamine is subsequently synthesized from tyrosine (Tyr). Improperly metabolized Phe in individuals with PKU or HPA, may restrict dopamine synthesis, pos-sibly causing the neurological impairments in individuals with untreated PKU. Alternatively, white matter abnormali-ties may occur in the brain of individuals with PKU. These abnormalities may reduce the speed with which signals are sent from neuron to neuron, leading to slower information processing. More research is necessary to conclusively de-termine the mechanism of neurologic damage in untreated PKU.3,4

IdentificationTesting for PKU is a part of newborn screening pro-

grams in all 50 states and many countries around the world. Typically, newborn screening tests blood from a heel-prick obtained before an infant goes home from the hospital. Each state will have guidelines regarding testing including births at the hospital, birth center, or home. Phe greater than 1000 µmol/L (16.7 mg/dL) are diagnosed with classic PKU; HPA is diagnosed in individuals with plasma Phe greater than 120 µmol/L (2 mg/dL) but less than 1000 µmol/L (16.7 mg/dL).

As newborn screening programs provide faster results, more babies are being identified and receiving treatment earlier than they had previously, raising controversy over whether it is appropriate to use plasma Phe levels for clas-sification. Currently, some infants with classic PKU may be diagnosed and treated before blood Phe rises above 1000 µmol/L (16.7 mg/dL), making the cut-off value irrel-evant.1,5 Genetic testing is available to determine the exact

EDITOR’S NOTE

The listing of commercial products is only for informational purposes and does not indicate endorsement.

Nutrition Focus Vol. 28 #4 July/August 20132

type of mutation, or genotype, but reliable infor-mation on appropriate and effective treatment based on genotype is not yet available so these tests are not a routine part of diagnosis at many treatment centers.5

TREATMENT OF PKU AND HPA

Treatment GoalsThe goal of treatment for PKU and HPA is

to maintain blood Phe concentrations within a range that will prevent the development of neurological complications. For individuals with classic PKU, the ideal range of blood Phe concentrations is 120-360 µmol/L (2-6 mg/dL) for early childhood and immediately before and during pregnancy.1 This range remains ideal over the entire life course, but levels of less than 600 µmol/L (10 mg/dL) have been observed in adults without symptoms. Individuals with HPA are often able to maintain blood levels close to the ideal range without treatment, and some experts question whether treatment is necessary for individuals with HPA who consistently have blood Phe concentrations of less than 600 µmol/L (10 mg/dL) without treatment.1,6

Dietary TreatmentDietary restriction is the best studied and

most widely used treatment for PKU and HPA. Although some Phe is necessary for growth and development, the amount of Phe in the diet must be closely controlled to prevent toxic build up in the blood. As an amino acid, Phe occurs in all high protein foods. Smaller amounts of Phe also occur in low protein foods, such as fruits, veg-etables, and grains. The amount of these foods an individual is able to consume depends on the Phe tolerance or the amount of dietary Phe an individual is able to consume and remain within the therapeutic range of blood Phe levels. Genotype has not been found to be a reliable predictor of Phe tolerance. Registered dietitians determine individual Phe tolerance through careful observation and adjustment of Phe intakes.5 Individuals with PKU or HPA require lifelong monitoring of blood levels and Phe intake because Phe tolerance may change with age or changes in BMI and body composition.7

In classic PKU Phe tolerance is too low to allow those with PKU to achieve a nutritionally complete diet without the use of high protein, Phe-free medical foods (formulas). Phe-free formulas provide an adequate amount of protein, as well as sufficient amounts of vitamins and minerals to support normal growth and development.8 The cost of Phe free formulas may be covered by medical insurance or state

wholesale purchase and distribution programs depending on local regulations. The interdisciplinary team can assist families by advocating for benefits from insurance provid-ers and connecting families with local resources. Patients supplement their formula with a variety of low protein foods, mainly fruits and vegetables. Individuals must care-fully measure portions of low-protein foods to keep their Phe intake below their Phe tolerance level.

NOTE:Theterm“medicalfood”isusedtodescribeformulasforthetreatmentofPKUandotherdisorders.Medicalfoodsareformulatedtobeconsumedoradministeredenterallyunderphysiciansupervisionandareintendedforthespecificdietarymanagementofadiseaseorconditionwithdistinctivenutritionalrequirements.

Figure1.Autosomalrecessiveinheritance

Figure2.Phenylalaninemetabolism

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Infants with classic PKU cannot rely solely on breast-milk as a food source because it contains Phe. The RD works with the parent and other members of the interdisci-plinary team to supplement intake of breastmilk with Phe-free formula usually using a schedule of alternating formula and breastmilk feedings.

HPA causes a less severe rise in blood Phe levels so, Phe-free formulas may not be required to maintain blood Phe levels within a safe range. However, the treatment of HPA may include some degree of high protein food restric-tion in order to maintain serum Phe levels within the thera-peutic range. The level of restriction is dependent on the amount of residual enzyme activity. Registered dietitians monitor individual intake to ensure nutritional deficiencies do not occur.

Nutrients of Concern with TreatmentAlthough the dietary treatment of PKU is necessary to

prevent negative neurological outcomes, the therapeutic diet restricts several nutrients known to be important to nor-mal growth and development. As an essentially vegan diet, natural sources of calcium, omega- 3 fatty acids, vitamin B12, iron, and zinc are limited. Although Phe-free formulas provide adequate amounts of all of these nutrients, nutri-ent deficiencies may develop in children who do not drink the full amount of formula prescribed to them.8 Addition-ally, PKU may affect the metabolism of other nutrients, possibly resulting in increased needs. Children undergoing dietary treatment of PKU have been observed to have iron deficiency even with iron intakes greater than the RDI. The mechanism for this deficiency is unknown, but supports the need to closely monitor children with PKU for nutritional deficiencies.9

Other TreatmentsAdditional therapies have

been introduced as a means to increase Phe tolerance and decrease the level of dietary restriction. These therapies include supplementation with large neutral amino acids (LNAA) and pharma-ceuticals that act as a cofac-tor to residual PAH. LNAA supplementation, provided at some treatment centers, may allow consumption of a larger proportion of protein from natural sources, instead of from Phe-free formula, by reducing the transport of Phe into the brain and increasing Phe tolerance.10

A pharmaceutical version of tetrahydrobiopterin (BH4), a cofactor of the PAH enzyme, has become available in the United States. Somewhere between 10% and 60% of patients with PKU or HPA are responsive to BH4 therapy, which reduces blood Phe concentrations and increases dietary Phe tolerance. In general, patients with higher Phe tolerance are more likely to respond to BH4 treatment. Fine-tuning of the appropriate dose and Phe tolerance over the first year of treatment requires continued close monitor-ing by both a physician and a dietitian.11 Both of these treat-ments may not eliminate the need for Phe-free formula.

GROWTH AND BODY COMPOSITIONAlthough the therapeutic diet for the treatment of PKU

is necessary to prevent negative neurological outcomes, the restrictive nature of the diet, especially the alteration of the type and amount of protein consumed, raises concerns about growth restriction and alteration of body composi-tion. Protein restriction is known to cause growth restric-tion in a typically developing population. However the goal of the therapeutic diet is to provide adequate protein with an appropriate amount of Phe.

Because the primary protein source for people with PKU is individual amino acids and not complete protein, studies have examined both the height and body composition of patients with PKU. These studies are limited, at least par-tially because of the rare nature of the disease. One a litera-ture review found that most studies observed some reduc-tion in height compared to standard growth curves. None, however, observed a reduction in height that was outside a range that was typical for healthy children.12 Some of these studies were conducted prior to the year 2000 and therefore do not reflect current practices in the dietary management

Table 1 - Prevalence of PAH Deficiency by Population

Population PAH Deficiency in Live Births

Carrier Rate

Citation

Turks 1:2,600 1/26 Ozalp et al [1986]Irish 1:4,500 1/33 DiLella et al [1986]Northern European origin, East Asian

1:10,000 1/50 Scriver & Kaufman [2001]

Japanese 1:143,000 1/200 Aoki & Wada [1988]

Finnish, Ashkenazi Jewish 1:200,000 1/225 Scriver & Kaufman [2001]

African ~1:100,000 ? AnecdotalSource:MitchellJJ,ScriverCR.Phenylalaninehydroxylasedeficiency.In:PagonRA,BirdTD,DolanCR,StephensK,AdamsMP,eds.GeneReviews.Seattle(WA):UniversityofWashington,Seattle.2013.

Nutrition Focus Vol. 28 #4 July/August 20134

of PKU.13 Recent studies have found that patients with early detected and continuously treated PKU do not have significant differences in height compared with typically developing peers.14

There has been concern that children with PKU may weigh more than children without PKU.15-18 One study found a high rate of obesity among children with PKU despite reported energy intakes less than estimated needs, suggesting that PKU may alter metabolic rate. However, this result may have been caused by participants who, either purposely or inadvertently, underestimated their food intakes.8 Another study found that individuals with PKU had higher body fat percentages across all BMIs. This was especially true of adolescent girls.19 Other reports indicate no differences associated with PKU.14,20 A recent study found no differences in body composition, overweight, and obesity between 89 individuals with PKU and 79 controls.20

The possibility of increased risk of growth alterations and the need for a specialized diet makes monitoring espe-cially important in children with PKU. The interdisciplin-ary team should closely monitor weight, height or length, as well as OFC for young children. Weight for length/height or BMI should be calculated, depending on the age of the child. Trends can be evaluated by plotting measurements on the appropriate growth chart.

PKU/HPA AND QUALITY OF LIFEAlthough normal development is expected in individuals

with early and continuously treated PKU, frequent monitor-ing of Phe levels by blood test and adherence to a restricted diet may affect their quality of life. Phe-free formulas are constructed of individual amino acids instead of plant or animal proteins found in food, and therefore taste different than most conventional foods. This taste may not remain acceptable to individuals with PKU as they try other foods over the course of their life. In general, adherence to diet decreases with increasing age.21 The restrictive diet also sometimes requires individuals with PKU to eat other foods than their friends or family. This can cause some individu-als with PKU to feel isolated. A social worker, as a member of the interdisciplinary team, can assist patients and their families in navigating social complications of PKU and can act as an advocate for the patient in interactions with the school system and other healthcare providers.

EDUCATION FOR CHILDREN WITH PKUAs with any chronic condition, children with PKU need

to learn to manage their own diet as part of a program geared to the developmental level of the child. A previous NUTRITON FOCUS article has addressed this issue in detail. See RESOURCE #1.

DIETARY RESTRICTION Restricting access to certain foods has been associated

with childhood overweight, and a decreased ability for a child to respond to his own satiety cues, increasing the risk of becoming overweight.22-25 The treatment for PKU requires dietary restriction in order to prevent neurological complications. It is unclear if this type of therapeutic re-striction has a similar affect on eating habits and the risk of becoming overweight.

A small study at the University of Washington Christine M. Trahms Program for Phenylketonuria examined this question by asking parents to complete a survey about feed-ing practices regarding their child with PKU or HPA and an unaffected sibling. The study found parents of children with PKU do not impose a greater degree of dietary restric-tion on children with PKU compared to unaffected siblings, but the sample size did not allow the detection of subtle differences.26 Additional research is necessary to determine if differences in restrictive eating behavior are affected by the degree of therapeutic diet restriction, and to clarify the impact PKU has on a parent’s perception of their child’s weight.

SUMMARYPKU and HPA are metabolic disorders identified at birth

that require dietary restriction of the amino acid Phe for optimal outcomes. Patients that are diagnosed early in life through newborn screening and are continuously treated are expected to grow and develop typically. Ideally, children with PKU will be treated by an interdisciplinary team that includes at a minimum a registered dietitian, a pediatrician, a social worker, and a genetic counselor. This team can address the nutrition and medical needs of the patient and their family as well as assist the family in receiving neces-sary services and planning for the future.

Nutrition Focus Vol. 28 #4 July/August 20135

CASE STUDYThecasestudybelowfollowsanow12-yearoldboyfromthe“PKUperspective.”Hissituationisunique,buthighlightstherolesofdifferentcareproviders,theneedforeffectivecommunicationandcollaboration,andtheroleofadvocateandcasemanagerassumedbyhismother.

0 to 6 monthsKeane and his twin sister were diagnosed with Down

syndrome (trisomy 21) shortly after birth. Following rou-tine newborn screening, an elevated blood phenylalanine (phe) level was noted in Keane. A repeat sample was ob-tained that showed a blood phe of 21 mg/dL (1260 µmol/L) with tyrosine in the normal range. Keane was still hospi-talized at that time, and a phe-restricted diet was started when he was 11 days old. The PKU Clinic RD was in close communication with the RD and staff at the hospital. Ini-tially, phe-free formula was provided. As Keane’s blood phe levels came down, standard infant formula was added. Amounts were titrated, and an intake of about 60 mg phe/kg allowed for blood phe levels in the desired range (2-6 mg/dL).

Keane was discharged from the hospital at age 2 weeks, with the diagnoses of Down syndrome, PKU, and an atrio-ventricular (AV) canal defect that was detected by ultra-sound. His family was told that the cardiac problem was stable and would probably require surgery when Keane was 3 or 4 months of age. His twin sister had a significant cardiac defect that would require intervention sooner.

Keane was seen in the PKU Clinic for the first time at age 3 weeks. By this visit, Keane was taking six 2-ounce bottles every 24 hours and weight gain was appropriate. His formula prescription was 35 grams Enfamil® + 16 grams Phenyl-Free® 1 + water to 12 ounces. Keane’s family and the PKU Clinic staff were in close communication. Blood phe levels were measured weekly, then every two weeks, then monthly by 6 months. His formula prescription was adjusted to meet increased needs related to growth and in response to blood phe levels outside the goal range. During his first 6 months, Keane had several URIs and was admit-ted to the children’s hospital with pneumonia and bronchi-tis.

7 to 12 monthsComplementary foods were introduced at age 7 months.

This decision was made based on Keane’s developmen-tal readiness. His parents met with the PKU Clinic RD to discuss the approach. Small, measured amounts of low-phe pureed foods were offered to provide <15 mg phe per day. Educational materials were provided, and Keane’s family was encouraged to share this with everyone involved in his care and feeding.

During this time, Keane received motor therapy services through the local early intervention program. When the

therapist began to work on feeding skills, the PKU Clinic RD and early intervention staff would have conversations about the best foods to use in therapy and to promote good blood phe levels. For example, when the occupational therapist suggested thickening the pureed foods offered to Keane, the PKU Clinic RD suggested using low protein porridge instead of the traditional rice cereal.

By Keane’s first birthday, he was sitting and starting to eat foods with more texture, including finger foods (low protein breadsticks, muffins prepared at home). His blood phe levels were stable and in the desired range. His intake at age 1 year provided about 30 mg phe from food, and he was taking about 24 ounces formula daily. Constipation was managed with fruit and fruit juice.

1 to 3 yearsAt age 14 months, a transition from Enfamil® to cow’s

milk was made in the formula preparation. He started to feed himself at age 15 months, and was starting to walk at around 20 months of age.

Keaneandhisfamily

Keane,agealmost12

Nutrition Focus Vol. 28 #4 July/August 20136

Keane continued to receive early intervention services. The feeding therapist was helping Keane learn to eat foods with more texture. Keane began to participate in the cen-ter’s feeding group when he was age 2 ½ years. The early intervention team worked with the PKU Clinic RD to identify appropriate foods to offer. By age 3 years, Keane was taking formula from a sippy cup. (See RESOURCE #2 for information about feeding problems and children with metabolic disorders).

In addition to well-child care and early intervention services, Keane’s family also participated in monthly PKU Clinic visits. At these visits, Keane’s growth would be evaluated, nutrition assessment completed, brief neurologic exam conducted, and blood collected to monitor blood phe and tyrosine levels. The clinic’s group format allowed for a parent education group at each visit, where families could discuss issues related to PKU management.

Keane’s PKU management was excellent. The majority of blood phe levels were in the desired range, and those that were outside the range could be explained by illness and/or changes in growth rates. His family kept meticulous re-cords of his intake. ”Lower phe” foods could be measured with household measures, but a gram scale was used to measure portions of foods with moderate amounts of phe. The food record was a good communication tool between care providers and provided the clinic staff with an accurate representation of Keane’s intake. His mother added other information to the records – sleep and activity patterns, bathing records, bowel history – and the record also be-came an important communication tool for the “non-PKU” parts of Keane’s care.

Table – Summary of Keane’s intake and issues, milestones at specific agesIn addition to a standard, age-appropriate dose of non-fat soluble multivitamins, the following should be given.5

Age Typical Intake Specific Issues/Concerns12 months 2 oz pear or white grape juice

1 Tbsp pureed prunes2 Tbsp mashed banana2 Tbsp applesauce thickened w/low protein porridgeBites of low protein breadsticks, muffins, crackers24 oz formula (Phenyl-free® 1 + Enfamil®)

• Finger foods introduced ~12 months• Constipation managed with fruit and fruit juice

14 months 40 g banana (~1/3 medium banana)2 low protein graham crackers4 Tbsp applesauce56 g squash (~3 ½ Tbsp)28 oz formula (Phenyl-free® 1 + Enfamil®)

• Working with therapist to increase accepted textures

• Transition from Enfamil® to cow’s milk in formula

30 months Foods with increasing texture: Rice Chex®, low pro-tein cookies, low protein onion rings (chips), cauli-flower; pureed squash, carrots, apricots36 oz formula (Phenyl-free® 2 + milk)

• Participates in feeding group at early interven-tion center

• Continuing to work on increasing texture of foods

• Formula from a sippy cup

5 years Low protein pasta with sauce, fruits, vegetables, gold-fish® crackers to provides about 90 mg phe36 oz formula (Phenyl-free® 2 + milk)

• Feeding-related goals incorporated into Ke-ane’s education plan

• PKU education continues (e.g., “yes” and “no” foods)

11 years ½ oz goldfish® crackers2 Tbsp peaches½ oz low protein pasta with 15 g tomato soup1 slice low protein bread with 1 tsp jelly13 grams Rice Chex®

½ rice cake2 Tbsp pears48 oz formula (Phenyl-free® 2 + milk)

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4 to 5 yearsKeane was enrolled in a developmental preschool after

earl y intervention services ended. The PKU Clinic RD and Keane’s mother provided information about his diet to his teachers and other school staff. He continued to receive therapies, and nutrition and related goals were incorporated as appropriate. For example, it was recommended that Ke-ane’s OT help to address oral sensitivities to make effective toothbrushing possible. PKU management continued to be excellent. Blood phe levels were in good control. Adjust-ments were made to Keane’s food pattern to allow more phe from food as his intake of solid food increased and to meet increased appetite and needs associated with growth and physical activity.

Keane began to be involved in PKU management as de-velopmentally appropriate, for example, identifying “yes” food and “no” foods and asking a parent about a food if he was unsure about whether or not he could eat it. Keane participated in PKU Clinic nutrition education activities and attended clinic regularly. (See RESOURCE #1 for ad-ditional details about nutrition education for children with a metabolic disorder using a developmental approach).

Elementary school and beyondKeane was enrolled in kindergarten at age 5 in a special

education classroom. He received speech, physical, and occupational therapies at school and speech therapy outside of school. In subsequent years, he was in a combination of special education and mainstream classrooms.

From a nutrition perspective, his family worked closely with the school to make sure his diet needs were met. They arranged several meetings with administrators, teachers, and food service staff. The PKU Clinic provided support, sometimes joining the meetings through conference calls, and providing documentation and information. Examples of modifications to the school menu were provided as well as recommendations for substitutions for high- and moderate-phe foods.

Keane’s mother maintained close communication with Keane’s teachers, including information about PKU and food. His teachers knew what types of substitutions they could make (or if substitutions were needed) when stu-dents brought birthday treats or when there were other food-related activities. They made sure his mother knew if substitutions were made so that she could adjust his intake during the rest of the day, if needed. Keane’s peers were aware of PKU; he drank formula at school as part of meals and snacks.

Keane and his family continue with excellent PKU management. It continues to be an important piece of life. The strong foundation and straightforward approach allow Keane and his family to be able to focus on other aspects of their lives without compromising PKU management.

REFERENCES1. Mitchell JJ, Scriver CR. Phenylalanine hydroxylase deficiency. In: Pagon RA,

Bird TD, Dolan CR, Stephens K, Adams MP, eds. GeneReviews. Seattle (WA): University of Washington, Seattle. 2013.

2. Mitchell JJ, Trakadis YJ, Scriver CR. Phenylalanine hydroxylase deficiency. Genetics in Medicine 2011;13(8):697-707.

3. Christ, Moffitt, Peck, White, Hilgard. Decreased functional brain connectiv-ity in individuals with early-treated phenylketonuria: Evidence from rest-ing state fMRI. Journal of Inherited Metabolic Disease 2012;35(5):807-816.

4. Janos AL, Grange DK, Steiner RD, White DA. Processing speed and execu-tive abilities in children with phenylketonuria. Neuropsychology, 2012 (online).

5. Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet 2010;376(9750): 1417-27.

6. Hanley WB. Non-PKU mild hyperphenylalaninemia (MHP)-the dilemma. Molecular Genetics and Metabolism 2011;104(1-2):23-6.

7. Rohde C, Mutze U, Weigel JF, Ceglarek U, Thiery J, Kiess W, Beblo S. Unrestricted consumption of fruits and vegetables in phenylketonuria: No major impact on metabolic control. European Journal of Clinical Nutrition 2012;66(5):633-8.

8. Acosta PB, Yannicelli S, Singh R, Mofidi S, Steiner R, DeVincentis E, Rouse B. Nutrient intakes and physical growth of children with phenylketonuria undergoing nutrition therapy. Journal of the American Dietetic Association 2003;103(9):1167-73.

9. Acosta PB, Yannicelli S, Singh RH, Elsas LJ, Mofidi S, Steiner RD. Iron status of children with phenylketonuria undergoing nutrition therapy assessed by transferrin receptors. Genetics in Medicine 2004;6(2):96-101.

10. Ahring KK. Large neutral amino acids in daily practice. Journal of Inherited Metabolic Disease, (online).2010.

11. Belanger-Quintana A, Burlina A, Harding CO, Muntau AC. Up to date knowledge on different treatment strategies for phenylketonuria. Molecu-lar Genetics and Metabolism 2011;104(Suppl):S19-25.

12. Dokoupil K, Gokmen-Ozel H, Lammardo AM, Motzfeldt K, Robert M, Ro-cha JC, MacDonald A. Optimising growth in phenylketonuria: Current state of the clinical evidence base. Clinical Nutrition 2012;31(1):16-21.

13. Allen JR, Baur LA, Waters DL, Humphries IR, Allen BJ, Roberts DC, Gaskin KJ. Body protein in prepubertal children with phenylketonuria. European Journal of Clinical Nutrition 1996;50(3):178-186.

14. Huemer M, Huemer C, Moslinger D, Huter D, Stockler-Ipsiroglu S. Growth and body composition in children with classical phenylketonuria: Results in 34 patients and review of the literature. Journal of Inherited Metabolic Disease 2007;30(5):694-699.

15. Belanger-Quintana A, Martinez-Pardo M. Physical development in pa-tients with phenylketonuria on dietary treatment: A retrospective study. Molecular Genetics and Metabolism 2011;104(4):480-484.

16. Burrage LC, McConnell J, Haesler R, O’Riordan MA, Sutton VR, Kerr DS, Mc-Candless SE. High prevalence of overweight and obesity in females with phenylketonuria. Molecular Genetics and Metabolism, (online). 2012

17. Scaglioni S, Verduci E, Fiori L, Lammardo AM, Rossi S, Radaelli G, Giovan-nini M. Body mass index rebound and overweight at 8 years of age in hy-perphenylalaninaemic children. Acta Paediatrica 2004;93(12):1596-1600.

18. White JE, Kronmal RA, Acosta PB. Excess weight among children with phenylketonuria. Journal of the American College of Nutrition 1982;1(3):293-303.

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19. Albersen M, Bonthuis M, de Roos NM, van den Hurk DA, Carbasius Weber E, Hendriks MM, Visser G. Whole body composition analysis by the BodPod air-displacement plethysmography method in children with phenylke-tonuria shows a higher body fat percentage. Journal of Inherited Metabolic Disease, (online).2010

20. Rocha JC, van Spronsen FJ, Almeida MF, Soares G, Quelhas D, Ramos E, Guimaraes JT, Borges N. Dietary treatment in phenylketonuria does not lead to increased risk of obesity or metabolic syndrome. Molec Genet Metab 2000;107(4):659-663.

21. MacDonald A, Gokmen-Ozel H, van Rijn M, Burgard P. The reality of dietary compliance in the management of phenylketonuria. Journal of Inherited Metabolic Disease 2010;33(6):665-70.

22. Faith, et al. Parent-child feeding strategies and their relationships to child eating and weight status. Obesity Research 2004;12(11):1711-1722.

23. Francis, Hofer, Birch. Predictors of maternal child-feeding style: maternal and child characteristics. Appetite 2001;37(3):231-43.

24. Thompson ME. Parental feeding and childhood obesity in preschool-age children: Recent findings from the literature. Issues in Comprehensive Pediatric Nursing 2010;33(4):205-267.

25. Johnson SL, Birch LL. Parents’ and children’s adiposity and eating style. Pediatrics 1994;94(5):653-661.

26. Bailey S. Restricted eating behavior in children with PKU and HPA. Unpublished thesis. University of Washington, Seattle. 2012.

RESOURCES1. Trahms C, Heffernan J, Ogata B. 2010 Nutrition Education for the Child

with a Metabolic Disorder. Nutrition Focus, 2010: Vol 25, #2 (Sept/Oct); 1-8.

2. Pantalos D, Warren J. Feeding Problems in Metabolic Disorders. Nutrition Focus, 2011: Vol 26, #4 (July/Aug); 1-9.

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1. The goal of treatment for PKU and HPA is to maintain blood Phe concentrations:

a. As low as possible b. Between 2 and 6 mg/dLc. Greater than 10 mg/dLd. Within a range that will prevent the development of

neurological complications; this is different for each individual

2. Which of the following BEST describes phenylketonuria (PKU)

a. A disorder of dopamine metabolismb. Allergy to the amino acid phenylalaninec. A metabolic disorder that affects an enzyme required

for the conversion of phenylalanine to tyrosined. A metabolic disorder that results in negative neuro-

logic outcomes, including intellectual disability

3. Newborn screening for PKU:a. Has reduced the incidence of PKUb. Is routine in all 50 states and many countries c. Includes genetic testing to identify the specific muta-

tiond. Is only done if there is a family history of metabolic

disorders

4. Dietary treatment for PKU:a. Is a low-protein dietb. Is based on an individual’s genotypec. Includes elimination of dietary phenylalanine (Phe)d. Depends on the Phe tolerance (amount of dietary Phe

an individual can consume and maintain goal blood Phe levels)

5. True or false: With classic PKU Phe tolerance is too low to achieve a nutritionally complete diet without the use of high protein, Phe-free formulas (medical foods):

a. True. Phe-free formulas provide an adequate amount of protein, as well as sufficient amounts of vitamins and minerals

b. True. Individuals with PKU should not eat food and require formulas/medical foods

c. False. Most individuals with PKU only need formula/medical food during infancy

d. False. Medical foods/formulas are too expensive to be used by most individuals with PKU

6. The food pattern of an individual with classic PKU is mostly likely to consist of:

a. Low protein foods, fruits and vegetablesb. Fruits and vegetables, grains, medical food/formulac. Measured amounts of fruits and vegetables, low pro-

tein foods, grainsd. Measured amounts of low protein foods, fruits, veg-

etables, medical food/formula

7. Children with PKUa. Have lower BMIs than peers without PKUb. Are significantly shorter than peers without PKUc. Have higher energy needs than peers without PKUd. None of the above

8. Infants with classic PKUa. Should receive no breastmilkb. Should be exclusively breastfedc. Should have solid foods introduced at age 8 monthsd. Can often be breastfed, usually using a schedule of

alternating formula and breastmilk feedings

9. Issues related to PKU that may affect quality of life include all of the following, EXCEPT:

a. Restrictive dietb. Frequent blood tests diet and blood monitoringc. Low protein diet interferes with neurotransmitter pro-

ductiond. Palatability of low protein foods and/or Phe-free for-

mulas as individuals try other foods over the course of their lives

10. Ideal treatment for PKU includes the involvement of an interdisciplinary team. Which of the following is NOT an example of a team member and/or role as described by the article:

a. The dietitian can conduct a neurologic evaluation dur-ing the nutrition assessment

b. Members of the team can advocate for benefits from insurance providers and connecting families with local resources

c. A genetic counselor can assist families in determining the risk of having another child with PKU, or of a fam-ily member being a carrier

d. A social worker can assist patients and their families in navigating social complications of PKU and can act as an advocate for the patient in interactions with the school system and other healthcare providers