Post on 30-Mar-2015
PKU in adolescents and adults
Andrew Morris
Royal Manchester Children’s Hospital
Manchester PKU patients
0
10
20
30
40
50
60
0-5 6-10
11-15
16-20
21-25
26-30
31-35
36-40
41-45
46-50
51-55
56-60
61-65
children (n=115)
adults (n=211)
Number
Age (yrs)
• 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
Adult PKU management
Prevention of
• Damage to children of PKU mothers
• Nutritional problems
• Late neurological problems (?)
PKU & Pregnancy
• Low risk of child having PKU (1:100)
• High risk of child being damaged by mother’s high phenylalanine levels
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
Congenital heart disease
International study
Diet pre- 0/23conception (0%)
Diet after 10 34/235weeks gestation (14%)
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
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
Adult PKU management
Prevention of
• Damage to children of PKU mothers
• Nutritional problems
• Late neurological problems (?)
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
0
100
200
300
400
500
600
strict
n=25
relaxed
n=30
normal
n=29
Vitamin B12 levels in PKUs on & off diet
B12levelin
blood(ng/l)
Diet :
1 3 6Pts with low B12
NormalRange
Adult PKU management
Prevention of
• Damage to children of PKU mothers
• Nutritional problems
• Late neurological problems (?)
Adults with PKU
High phenylalanine levels cause
• Minor symptoms in some patients
– Poor concentration
– Lethargy
– Irritability
Adults with PKU
High phenylalanine levels cause
• Minor symptoms in some patients
• Abnormalities on brain scans – White matter
– Reversible if phenylalanine lowered
Normal White matter changes
Probably due to increased water content
Adults with PKU
High phenylalanine levels cause
• Minor symptoms in some patients
• Abnormalities on brain scans
• Neurological problems (very rare)
Stiffness
Poor balance
Epilepsy
Poor short term memory
• Very rare• Most patients had poor early control• Often reversible on restarting diet
Neurological problems after stopping PKU diet
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
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
Adolescents: recommendations
• Dietary treatment
• Phenylalanine levels 120-700 mcmol/l
Not worth pursuing if leads to
• Family breakdown
• Serious nutritional problems
What are we achieving?
%phe
samples outside target range
Age0
10
20
30
40
50
60
70
80
90
0 2 4 6 8 10 12 14 16 18 20
Target range 120-360 120-480 120-700
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
Treatment of PKU
• Phenylalanine restricted diet
• Amino acid supplements
• Low protein products
• Vitamins & Minerals
• Monitoring of phenylalanine levels
Adult PKU: neurological abnormalities
Brisk reflexes
Tremor
• Asymptomatic
• Common
• On or off diet
Scan abnormalities and phenylalanine level
Severity of abnormality on scan
Phe
0 5 10 15 20 25
500
1000
1500
2000
Phenylketonuria
Phenylalanine TyrosinePA Hydroxylase
BH4 BH2
DHPR
Phenylketones
Published guidelines
UK (1993)• pre-school: 120-360
µmol/l (2-6 mg/dl)• school age: 120-480
µmol/l (2-8 mg/dl)• adolescence: 120-
700 µmol/l (2-11.7 mg/dl)
German (1999)• <10 y 40-240 µmol/l
(0.7-4 mg/dl)• 10-15 y 40-900
µmo/l(0.7-15 mg/dl)
• >15 y 40-1200µmol/l (0.7-20 mg/dl)
Number ofadult patients
Number ofcentres
Babies in 1999
>50 6 26
20-50 5 1
<20 65 6
Management of PKU adults in UK
UCH is the largest centre with 270 adult patients