1. PKU in adolescents and adults
Andrew Morris
Royal Manchester Children’s Hospital

2. Manchester PKU patients60 50
children (n=115)
adults (n=211) 40
Number 30 20 10
0-5 6-
11-
16-
21-
26-
31-
36-
41-
46-
51-
56-
61- 10 15 20 25 30 35 40 45 50 55 60 65
Age (yrs)

3. High phenylalanine levels are harmful to the developing brain
Phenylalanine must be strictly controlled in infancy, childhood and in pregnancy
Stopping the PKU diet after childhood does not have a major effect on IQ

4. Adult PKU management Prevention of Damage to children of PKU mothers
Nutritional problems
Late neurological problems (?)

5. PKU & Pregnancy Low risk of child having PKU (1:100)
High risk of child being damaged by mother’s high phenylalanine levels

6. Untreated Maternal PKU
Adverse effects on infant
Mental retardation (92%)
Abnormally small head (73%)
Low birth weight (40%)
Congenital heart disease (12%)
Abnormal facial appearance
Lenke & Levy, 1980

7. Congenital heart disease
International study
Diet pre- 0/23
conception (0%)
Diet after /235
weeks gestation (14%)

10. Maternal PKU: when to start strict diet
International study recommended
levels down by 10 weeks gestation
BUT - takes time to get levels down
- vomiting in early pregnancy
Pre-conception
If unplanned as soon as possible
If very late consider termination

11. Maternal PKU: Problems
Diet is difficult
Cost
Waiting to conceive whilst on diet
refer to reproductive medicine after 6 months
Vomiting
Learning difficulties in some patients
Poor support from some doctors

12. Adult PKU management Prevention of Damage to children of PKU mothers
Nutritional problems
Late neurological problems (?)

13. Nutrition in PKU Adults
On PKU diet
Supplements often taken erratically
Off PKU diet
Diet often low in red meat & dairy foods
low in vitamin B12
iron
calcium

14. Vitamin B12 levels in PKUs on & off diet
strict
relaxed
normal
600
n=25
n=30
n=29
500
Normal
Range
B12
level in
blood
(ng/l)
400
300
200
100
Pts with low B12 1 3 6

15. Adult PKU management Prevention of Damage to children of PKU mothers
Nutritional problems
Late neurological problems (?)

16. Adults with PKU High phenylalanine levels cause
Minor symptoms in some patients
Poor concentration
Lethargy
Irritability

17. Adults with PKU High phenylalanine levels cause
Minor symptoms in some patients
Abnormalities on brain scans
White matter
Reversible if phenylalanine lowered

18. increased water content
Normal
White matter changes
Probably due to
increased water content

19. Adults with PKU High phenylalanine levels cause
Minor symptoms in some patients
Abnormalities on brain scans
Neurological problems (very rare)

20. Neurological problems after stopping PKU diet
Stiffness
Poor balance
Epilepsy
Poor short term memory
Very rare
Most patients had poor early control
Often reversible on restarting diet

21. Adults with PKU High phenylalanine levels cause
Minor symptoms in some patients
Abnormalities on brain scans
Neurological problems (very rare)
Unknown effects in very long term
No early treated patients have yet reached 50 yrs

22. Adolescents with PKU
Poor dietary control may lead to disappointing exam results
No good studies
families with good dietary compliance also likely to encourage studying
randomised controlled trials not possible

23. Adolescents: recommendations
Dietary treatment
Phenylalanine levels mcmol/l
Not worth pursuing if leads to
Family breakdown
Serious nutritional problems

24. What are we achieving? % phe samples outside target range Age90 80 70 60 50 40 30 20 10
Age 2 4 6 8 10 12 14 16 18 20
Target range

25. Management of adults with PKU
PKU clinics provide information
Patients choose whether to stay on diet
Everyone needs regular review to
Support patients on diet
Prevent nutritional problems
Monitor for neurological problems
Ensure strict diet during pregnancy

27. Treatment of PKU Phenylalanine restricted diet Amino acid supplements
Low protein products
Vitamins & Minerals
Monitoring of phenylalanine levels

28. Adult PKU: neurological abnormalities
Brisk reflexes
Tremor
Asymptomatic
Common
On or off diet

29. Scan abnormalities and phenylalanine level
2000
1500
1000
500 5 10 15 20 25
Severity of abnormality on scan

30. Phenylketonuria PA Hydroxylase Phenylalanine Tyrosine BH4 BH2 DHPR
Phenylketones

31. Published guidelines UK (1993) pre-school: 120-360 µmol/l (2-6 mg/dl)
school age: µmol/l (2-8 mg/dl)
adolescence: µmol/l ( mg/dl)
German (1999)
<10 y µmol/l (0.7-4 mg/dl)
10-15 y µmo/l ( mg/dl)
>15 y µmol/l ( mg/dl)

32. Management of PKU adults in UK
UCH is the largest centre with 270 adult patients