Transcript Maternal PKU - NSPKU | The National Society for

PKU in adolescents and adults
Andrew Morris
Royal Manchester Children’s Hospital
Manchester PKU patients
60
50
children (n=115)
adults (n=211)
40
Number
30
20
10
0
0-5
610
11- 16- 21- 26- 31- 36- 41- 46- 51- 56- 6115 20 25 30 35 40 45 50 55 60 65
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 preconception
0/23
(0%)
Diet after 10
weeks gestation
34/235
(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
Vitamin B12 levels in PKUs on & off diet
Diet :
strict
relaxed
normal
600
n=25
n=30
n=29
500
B12
level
in
blood
(ng/l)
Normal
Range
400
300
200
100
0
Pts with low B12
1
3
6
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)
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
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
90
80
70
60
50
40
30
20
10
0
0
2
Target range 120-360
4
6
8
10
120-480
12
14
16
18
120-700
20
Age
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
Phe
2000
1500
1000
500
0
5
10
15
20
25
Severity of abnormality on scan
Phenylketonuria
PA Hydroxylase
Phenylalanine
Tyrosine
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: 120700 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)
Management of PKU adults in UK
Number of
adult patients
Number of
centres
Babies in 1999
>50
6
26
20-50
5
1
<20
65
6
UCH is the largest centre with 270 adult patients