Unmasking Male Depression: Understanding and Treating Adolescents and Adults
PKU in adolescents and adults
description
Transcript of PKU in adolescents and adults
PKU in adolescents and adults
Andrew Morris
Royal Manchester Children’s Hospital
Manchester PKU patients
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10
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0-5 6-10
11-15
16-20
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26-30
31-35
36-40
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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