1. Student ： Barnett Un Instructor ： RD. Jenny Weng Date : 12 月 21 日 Physical Development and Reassessment of Phenylalanine Tolerance in Adults with Phenylketonuria on Dietary Treatment 1

2. REF: (Van Calcar SC, 2012 ) 2 Phenylalanine pathway Phenyllactcate

3. Physical development in patient with phenylketonuria on dietary treatment: a retrospective study Amaya BQ and Mercedes MP. Mol Genet Metab. 2011 ;104(4):480-4. 3

4. 4 Introduction:  most PKU patients must follow a protein-restrictive diet, normal growth has become another fundamental concern in the follow-up of these patients.  The aim of this study was to evaluate the growth and physical development in PKU patients who were treated exclusively with diet in order to observe if there were differences with the normal population and if these differences depended on the age or the phenotype

5. 5 Study Design 158patients 61 MHP (>1800μmol/L) 28 Mild PKU (360-1200μmol/L) 35 Moderate PKU (1200-1800μmol/L) 34 Severe PKU (>1800μmol/L) Normal diet Phe-restrictive diet Weight, Height/Length and BMI 18 years of life 9 years of life Spanish general population Statistical analysis At birth At the time of diagnosis At 6 months and 12 months of age Annually >12 months At birth At the time of diagnosis At 6 months and 12 months of age Annually >12 months

6. 6 Results: The final height of PKU patients is as similar as the final height of Normal population

7. 7 Results: Z scores Weight Male Female

8. 8 Discussion: Overweight and Obesity:  Patients depend greatly on Phe-free (but high on calories) foods to satisfy their appetite.  some adolescents prefer to maintain the formulas they are used to, rather than transfer to “adult” formulas, and some of these presentations have a higher fat content than recommended because they are directed to a growing child, rather than an adult.  the avoidance of sporting activities due to the reported social isolation and anxiety of these patients.

9. 9 Conclusion:  Excessive weight gain was observed after the end of puberty in patients with the most severe phenotypes

10. High prevalence of overweight and obesity in females with phenylketonuria Burrage LC, McConnell J, Haesler R, O‘Riordan MA, Sutton VR and Kerr DS. Mol Genet Metab. 2012 ;107(1-2):43-8. 10

11. 11 CarbohydrateFatProtein Low Phe diet CarbohydrateFatProtein Overweight or Obesity ? ? Introduction:

12. 12 Study Design PKU patients (n=87) Cleveland (n=33) Houston (n=54) Male (n=14) Female (n=19) Male (n=31) Female (n=23) Age, weight, length/height and BMI Statistical analysis U.S. general population Retrospective time: 1990~2008 Low Phe diet Age : 2~19 years old Retrospective time: 1990~2008 Low Phe diet Age : 2~19 years old

13. 13 Results:  the percentage of overweight and obesity in the male patients was similar to the general population.  the prevalence of overweight and obesity in the female patients was 1.5 to 1.8 times higher than the general population.

14. 14 Discussion: Overweight and Obesity:  The patients may have less supervision regarding formula consumption and meal preparation which could result in higher calorie consumption  One hypothesis was that the low phenylalanine diet, which is typically rich in carbohydrate content, contributes to overweight or obesity in PKU patients

15. 15 Conclusion:  Females with PKU include the risk for overweight and obesity and methods for reducing this risk such as increased activity, healthy food selection, and possibly improved compliance with supplemental formula.

16. Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes MacLeod EL, Gleason ST, van Calcar SC and Ney DM. Mol Genet Metab. 2009 ;98(4):331-7. 16

17. 17 Introduction:  Reassessment of phe tolerance is becoming increasingly important as individual phe tolerance can improve with treatment and future advances with phenylalanine ammonia- lyase treatment.

18. 18 Study Design 8 PKU patients (male 4; female 4) 3-day food records Initial Phe tolerance 3-day food records Increased dietary Phe intake Blood Phe level in acceptable range Final Phe tolerance Statistical analysis Blood Phe level exceeds acceptable range Low Phe diet 5 subjects overweight Low Phe diet 5 subjects overweight

19. 19 Results: Sujects (male): 1,2,8,11

20. 20 Results:

21. 21 Discussion: Phe tolerance:  One explanation for greater than expected phe tolerance in our adult subjects is that their intake of dietary Phe was not adequate to support protein turnover and synthesis for their current body mass.  A past study showed that lower Fat free mass (FFM) and greater fat mass reduce the expression of Phe tolerance  Sex differentially affects the deposition of fat and muscle during puberty resulting in greater gains of FFM in males.

22. 22 Conclusion:  Reassessment of Phe tolerance with input from a dietitian may ultimately improve lifelong adherence to the PKU diet and overall health.

23. 23 Summary: Females with PKU Overweight and Obesity + Phe tolerance --

24. 24

25. REF: http://depts.washington.edu 25 Low Phenylalanine diet