Inherited Metabolic Disorders

Question 1

Phenylketonuria definition

Answer 1

• amino acidopathy: issues with conversion of phenylalanine to tyrosine (adding hydroxyl group)
• too much phenylalanine (toxic to neurons) and lack of tyrosine leads to symptoms
• delays neurodevelopment

Question 2

PKU symptoms (if intreated)

Answer 2

• severe learning difficulties
• behavioural problems
• seizures
• lack of pigmentation

Question 3

Why are low protein products required?

Answer 3

• to provide kcals
• to provide variety in diet
• prevent hunger

Question 4

How to monitor PKU

Answer 4

• guthrie test

- monitor dried blood sample on paper (same as newborn screening)

Question 5

Aims of PKU diet

Answer 5

• to keep Phe within normal recommended range whilst maintaining normal growth and development
• providing a balanced healthy and nutritious diet rich in Phe
• to prevent any symptoms developing relating to Phe

Question 6

Early treatment outcome

Answer 6

• maintain <400 mcmol/l in early childhood (up to age 10) results in near normal IQ
• for each 300 mcmol/l Phe IQ decreases by 0.5 SD

Question 7

Effects of high Phe on adults with PKU

Answer 7

• tremor, knee jerks and spastic paraparesis (may be due to B12 deficiency due to low meat consumption)
• MRI changes (may be reversible if follow a low Phe diet again)
• have reduced reaction time
• may have cognitive changes, depression, lack of concentration and irritability

Question 8

Enzyme enhancement therapy for PKU

Answer 8

• most PKU patients have residual Phe hydroxylase activity which could be exploited
• tetrahydrobiopterin (BH4) could be used as it is cofactor for hydroxylase and could encourage flux in the pathway
• phenylalanine ammonia lyase: converts Phe to trans-cinnamic acid instead of tyrosine

Question 9

Diet recommended for PKU

Answer 9

1) protein restriction (exchanges- where 1g is one exchange, assuming 1g contains 50mg Phe)- need to be especially strict in young children and pregnant women- can use special prescription low protein products to provide bulk, kcals and variety
2) protein substitutes (AA supplements with Phe removed) to meet 0.83g/kg/day in adults, these often contain vitamins/minerals/essential fatty acids
3) low protein foods (ie fruit and veg, fats, sugars, vegan cheeses)
4) micronutrient supplementation

Question 10

Dietary education for PKU sufferers

Answer 10

• sampling of low protein supplements and foods
• exchange calculation
• weighing
• menu planning
• practical sessions making low protein meals/snacks
• supermarket visit
• support with blood testing