PKU

Question 1

Inborn errors of metabolism

Answer 1

Rare, genetic
Defect in an enzyme leading to blockage in pathway
Effects are due to toxic accumulation of substrate
Often CNS involved
Single mutant gene

Question 2

PKU

Answer 2

Usually PAH (enzyme) deficient 
- degree varies none->25% activity 

Decreased brain protein synthesis + increased myelin turnover
=> inhibits neurotransmitter synthesis

Question 3

Prevalence

Answer 3

Wide ethnic + geographic variation

Common - Ireland, Turkey, Poland

Question 4

Biochemistry

Answer 4

Phe -> Tyr
- doesn’t occur when no/not enough PAH enzyme

So high Phe and low Tyr
- Tyr required from diet as not made

Question 5

Classification

Answer 5

Depending on residual enzyme activity

All children Phe >400umol/L should follow low PKU diet

Question 6

Classification:

Classic/severe

Answer 6

PAH activity <0.3%
Blood Phe >1200umol/L

Tolerate 250mg/d dietary Phe
Aim plasma Phe <360umol/L

Question 7

Classification

Moderate

Answer 7

Blood Phe 600-1200umol/L

Tolerate 200-700umol/L

Question 8

Classification

Mild

Answer 8

Partial PAH activity loss
Blood Phe 120-600umol/L

Follow normal diet

Question 9

Diagnosis

Answer 9

Routine neonatal screening
Heel prick test
If Phe >240umol/L

Question 10

Dietary management:

Protein supplement

Answer 10

No Phe
Supplies >75% protein requirements inc Tyr

Give small and frequent
- keep Phe levels steady throughout the day

Question 11

Dietary managment
Key elements (9)

Answer 11

Restriction
Daily allocation of dietary Phe
Suitable Phe-free protein supplement 
Prescription
Meeting normal energy needs
Provision of vit + min
Attention to essential FA status
Palatable diet that fits lifestyle
Avoid aspartame

Question 12

1 exchange

Answer 12

50mg Phe

1g protein

Question 13

Monitoring

Answer 13

Taken at standard time
Before protein substitute
May vary by 150umol/L day

Question 14

Monitoring

Target blood Phe

Answer 14

Age variable

>10yr = 120-700umol/L

Question 15

Monitoring

Frequency

Answer 15

0-4y = weekly
5-10y = fortnightly
>11yr = monthly

Question 16

Breastfeeding

Answer 16

Lower in Phe than whey-based formula (slightly)
Mother can eat normally

Give measured volume of Phe free formula before each feed to decrease appetite so less Phe intake

Question 17

Phe daily intake (babies)

Answer 17

Babies still need small level to prevent brain damage

Question 18

Bottle feeding

Answer 18

6-7 feeds/24hr

Normal formula given first followed by Phe free formula

Question 19

Introducing solid foods

Answer 19

6m
Start with 1-2tsp of low Phe foods
Offer after breast/formula
Can be low energy so need to incorporate higher energy food
Infant + second stage protein substitute

Question 20

Toddlers

Answer 20

Feeding problems common
Some protein supplements energy dense
Refusal to eat exchanges
Difficulty giving protein substitutes

Question 21

School children

Answer 21

Most have pack lunches
Best to avoid protein substitutes at school

Teach children to recognise Phe exchanges + portion sizes for when out of the home

Question 22

Teenagers

Answer 22

Some will rebel
Aim to keep Phe conc <700umol/L
Contact essential
- still growing, sets up for life

Question 23

Pregnancy

Teenagers

Answer 23

Education to girl + family regarding risk

Question 24

Pregnancy

Family planning

Answer 24

Strict diet before or soon after conception

Phe conc 100-250umol/L

Question 25

Illness

Answer 25

Maintenance of protein substitute
Other low Phe foods
High CHO drinks
Medications need to be aspartame free

Question 26

Diet for life

When off the diet (4)

Answer 26

Negative mood
Tremors + impaired co-ordination
Low QoL
Social isolation