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